Introducion 1

1. INTRODUCTION

1.1 MEDICINAL PLANTS

Medicinal plants are the plants which are used in the field of medicine due to having

medicinal properties. Some plants or their phytochemical constituents have been

proven to have medicinal effects by rigorous science or have been approved by

regulatory agencies such as the United States Food and Drug Administration

(USFDA) and European Food Safety Authority (EFSA). India is a country known for

ancient scripts, the number system and invention of zero and Vedas. Medicines in

India are used by about 60 per cent of the world's population. These are not only used

for primary health care not just in rural areas in developing countries, but also in

developed countries as well where modern medicines are predominantly used. While

the traditional medicines are derived from medicinal plants, minerals, and organic

matter, the herbal drugs are prepared from medicinal plants only.1-2

Use of plant parts as a source of medicine has been an ancient practice and is an

important component of the health care system in India. In the Indian systems of

medicine, most practitioners formulate and dispense their own recipes; hence this

requires proper documentation and research. In west also the use of herbal medicines

is growing with approximately 40 per cent of population reporting use of herb to treat

medical diseases within the past year. General Public, academic and government

interest in traditional medicines is growing rapidly due to the increase side effects of

the adverse drug reactions and cost factor of the modern system of medicine.3-5

There are approx 45,000 medicinal plant species in India, with concentrated spots in

the region of Eastern Himalayas, Western Ghats and Andaman & Nicobar Island. The

officially documented plants with medicinal potential are 3000 but traditional

practitioners use more than 6000. India is the largest producer of medicinal herbs and

is called the botanical garden of the world. There are currently about 250,000

registered medical practitioners of the Ayurvedic System, as compared to about

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700,000 of the modern medicine system. In rural India, 70 per cent of the population

depends on the traditional type of medicine like Ayurveda.6-8

In India, many forms of alternative medicines are available for those who do not want

conventional medicine or who cannot be helped by conventional medicine. Ayurveda

and Kabiraji (herbal medicine) are two important forms of alternative medicine that is

widely available in India.

Ayurvedic form of medicine is believed to be existent in India for thousands of years.

It employs various techniques and things to provide healing or relief to the ailing

patients. One of the think is that Ayurveda uses is medications of plant origin.

We have evidence of a traditional use of medicinal plants with the scripts in the

Atharva Veda that is more than 3000 years old. It is estimated that about 80,000

species of plants are utilized in some form or other by the different systems of Indian

medicine. The knowledge about plants and plant products is detailed, sophisticated,

and has evolved into a separate shastra itself, called Dravya Guna Shastra.

Plants have been studied on the basis of clearly defined biological parameters like

rasa (taste), vipaka (metabolic property), guna (quality), prabhava (biological effect)

and virya (potency). The codified traditions have about 25,000 plant drug

formulations that have emerged from such studies. In addition to this, over 50,000

formulations are believed to be existence in the folk and tribal traditions. All these

point to the deep passion and exhaustive knowledge about medicinal plants that have

existed in this land from time immemorial.9-10

1.2 IMPORTANCE11-15

Medicinal herbs are staging a comeback and herbal period is happening all over the

world. The herbal products today have symbol of safety in contrast to the

synthetics that are regarded as unsafe to life and environment. Although herbs had

been priced for their flavouring, medicinal, nutritional and other qualities for

centuries, the synthetic products of the modern age surpassed their importance, for

a while. Thus, now a d a y our blind dependence on synthetics is over and we are

returning to the naturals with hope of safety and security and also for other benefits.

More than one third of the world’s population relies on plants and plant extracts for

health care. Over 30% of the entire plant species is used for medicinal purposes at one

time or other. It is supposed that world market for plant derived drugs may account for

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about Rupees Twenty Thousand Crores. Presently, the contribution of India is less

than Rs.2000 crores. India export of raw drugs has steadily grown from Rs.130

crores in 1991-92 26% to Rs.165 crores in 1994-95. The annual production of

medicinal and aromatic plant’s raw material is worth about Rupees Two Thousands

Crores. This is approx to touch US $1150 up to the year 2000 and US $5 trillion up

to 2050.

This is estimated in developed countries like United States that plant drugs constitute

more than 25% of the total drugs, while in fast developing countries like India and

China, the contribution is more than 80%. However, the economic importance of

medicinal plants is very much to developing countries such as India comparison to

rest of the world. These countries provide more than two third of the plants used in

modern system for medicine and the health care system of rural and urban population

depend on indigenous systems of medicine. From the 245,000 higher plant species on

earth, more than 75,000 have medicinal value. India is one of the world’s Twelfth

biodiversity centres with the presence of over 45000 different plant species. India’s

diversity is unmatched due to the presence of sixteen different agro-climatic zones,

ten vegetation zones, twenty five biotic provinces and four hundred twenty six biomes

(habitats of specific species). From 45,000 plants approx 15000 to 20000 plants have

good medicinal value. Thus, only 7000 to 7500 species are used for their

medicinal values by traditional communities. In India, drugs of herbal origin have

been used in traditional medicine system such as Unani and Ayurveda since ancient

times. The Ayurveda System of medicine uses more than 700 species, Unani System

uses about 700, Siddha System uses about 600, Amchi System uses about 600

species and Modern medicine System around uses about 30 species. The drugs are

found either t he from of whole plant or t he form o f different organs, like stem,

bark, root, leaves, flower, seed, etc. Many drugs are prepared from plant

secretion such as resins, gum and latex. Even now Allopathic system of medicine

has adopted a number of plant-derived drugs which form an important place in the

modern pharmacopoeia. Some modern drugs are also obtained from plants e.g.

diosgenin, solasodine, ionone. Even not only, that plant-derived drug offers a stable

market worldwide, but also plants continue to be an important source for some new

drugs.

From ancient civilisations, India has been known to be rich country of medicinal

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plants. The forest in India is the principal repository in large numbers of

medicinal and aromatic plants, which are collected as raw materials for drugs

manufacturing and perfumery products. About 8,000 herbal remedies have been

codified in Ayurveda. In other Veda’s, The Rigveda (5000 BC) has recorded 67

medicinal plants, Yajurveda recorded 81 species, Atharvaveda (4500-2500 BC) have

290 species, Charak Samhita (700 BC) and Sushrut Samhita (200 BC) had described

properties and uses of 1100 and 1270 species respectively, Almost all have their

uses in compounding of drugs and these are still used in modern medicine with

classical formulations. In the Ayurvedic system of medicine, the ancient knowledge

and many valuable plants are being lost day by day at an alarming rate, Due to the

rapid depletion of forests, impairing the availability of raw drugs. Like other systems

of herbal medicines, Ayurveda has reached a very critical phase. More than 50% of

the tropical forests, the treasure house of plant and animal diversity have already

been destroyed. In India, forest cover is disappearing at an annual rate 1.5mha/yr.

What is left at present is only 8% as against a mandatory 33% of the geographical

area. Many valuable medicinal plants are under the verge of extinction. The Red Data

Book of India has 427 entries of endangered species of which 28 are considered

extinct, 124 endangered, 81 vulnerable, 100 rare and 34 insufficiently known species.

Medicines like Siddha, Unani Folk (tribal) and Ayurveda, are the major systems of

indigenous medicines. Among these systems, Ayurveda has a wide role and is

most developed and widely practised in India. Ayurveda dating back to 1500-800

BC has been an integral part of Indian culture. The term comes from the Sanskrit root

Au (life) and Veda (knowledge). As the name implies it is not only the science of

treatment of the disease but covers the entire range of happy Human life involving the

physical, metaphysical and the spiritual aspects. Ayurveda recognises that besides a

body balance, elements one has to have an enlightened state of consciousness, mind

and sense organs, if one has to be perfectly healthy. Ayurveda by and large is an

experience with nature and unlike in Western medicine, many of the concepts elude

scientific explanation. Ayurveda is beneficial as the natural system of health care all

over the world. Today Ayurveda system of medicine is being practised in countries

like Bhutan, Sri Lanka, Nepal, Bangladesh and Pakistan, while the traditional system

of medicine in the other countries like Mongolia, Tibet and Thailand i s appear to

inspire from Ayurveda. Plant medicines are also being used increasingly in

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Western country like Europe. Recently the US Government has established the

“Office of Alternative Medicine” at the National Institute of Health at Bethesda and

its support to alternative medicine includes basic and applied research in

traditional systems of medicines such as Ayurvedic, Chinese etc. with a view to

assess the possible integration of effective medications with modern medicines.

The development of pharmacopoeias i s dated back to 3000 BC, when the Chinese

were already using more than 350 herbal remedies. Ayurveda, the system of

herbal medicine in India, Sri Lanka and South-East Asia has more than 8000 plant

remedies and using around 45,000-70,000 plant species. China has demonstrated the

best traditional medicine use in providing the health care. China has

pharmacologically validated value and improved many traditional herbal medicines

and eventually integrated them in formal health care system.

The plants synthesise and preserve a variety of biochemical products, many of

which are extractable and a l s o used as raw material o r chemical feed stocks for

various scientific investigations. Many secondary metabolites of plant are important

and find use in a number of pharmaceutical compounds. However, a sustained supply

of a source material often becomes difficult due to the many factors like cultural

practices, diverse geographical distribution, environmental changes, labour cost,

selection of the superior plant stock and over exploitation by pharmaceutical industry.

Those plants which are used in Ayurveda can provide biologically active molecules

and lead structures for the development of modified derivatives with enhanced

activity and may reduced toxicity. The small fractions of flowering plants that have

so far been investigated have yielded approx 120 therapeutic agents of known

structure from about 95 species of plants. Useful plant drugs include vinblastine,

vincristine, podophyllotoxin, camptothecin, taxol, digitoxigenin, gitoxigenin,

digoxigenin, tubocurarine, codeine, aspirin, atropine, pilocarpine, morphine,

capscicine, allicin, curcumin, artemesinin and ephedrine among others. In many cases,

the crude extract of medicinal plants can be used also as medicaments. On the other

way, the isolation and identification of extract for the active principles and

elucidation of the mechanism of action of a drug is of paramount importance. Hence,

works in both mixture of traditional medicine and single active compounds are very

important, and we know the active molecule cannot be synthesised economically,

the product must be obtained from the plant cultivation. The scientific study of

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traditional medicines, derivation of drugs through bio prospecting and systematic

conservation of the concerned medicinal plants are thus having great importance.

1.3 CLASSIFICATION OF MEDICINAL PLANTS16-20

Over the 240,000 higher plant species on earth, about 75,000 species are reported to

have at least some medicinal value and around 5000 species have specific

therapeutic value. Some of these are classified according to the part used, habit,

habitat, therapeutic value etc, besides the usual botanical classification.

Based on part used

• Whole plant: Boerhaavia diffusa, Phyllanthus neruri

• Root: Dasamula

• Stem: Tinospora cordifolia, Acorus calamus

• Bark: Saraca asoca

• Leaf: Indigofera tinctoria, Lawsonia inermis, Aloe vera

• Flower: Biophytum sensityvum, Mimusops elenji

• Fruit: Solanum species

• Seed: Datura stramonium

Based on habit

• Grasses: Cynodon dactylon

• Sedges: Cyperus rotundus

• Herbs: Vernonia cineria

• Shrubs: Solanum species

• Climbers: Asparagus racemosus

• Trees: Azadirachta indica

Based on habitat

• Tropical: Andrographis paniculata

• Sub-tropical: Mentha arvensis

• Temperate: Atropa belladona

Based on therapeutic value

• Antimalarial: Cinchona officinalis, Artemisia annua

• Anticancer: Catharanthus roseus, Taxus baccata

• Antiulcer: Azadirachta indica, Glycyrrhiza glabra

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• Antidiabetic : Catharanthus roseus, Momordica charantia

• Anticholesterol: Allium sativum

• Antiinflammatory: Curcuma domestica, Desmodium gangeticum

• Antiviral: Acacia catechu

• Antibacterial: Plumbago indica

• Antifungal: Allium sativum

• Antiprotozoal: Ailanthus sp., Cephaelis ipecacuanha

• Antidiarrhoeal: Psidium gujava, Curcuma domestica

• Hypotensive: Coleus forskohlii, Alium sativum

• Tranquilizing: Rauvolfia serpentine

• Anaesthetic: Erythroxylum coca

• Spasmolytic : Atropa belladona, Hyoscyamus niger

• Diuretic: Phyllanthus niruri, Centella asiatica

• Astringent: Piper betle, Abrus precatorius

• Anthelmentic: Quisqualis indica, Punica granatum

• Cardiotonic: Digitalis sp., Thevetia sp.

• Antiallergic: Nandina domestica, Scutellaria baicalensis

• Hepatoprotective: Silybum marianum, Andrographis paniculata

1.4 PROCESSING AND UTILIZATION OF MEDICINAL PLANTS21-27

Medicinal compounds can be present in different parts of the plant like root, stem,

bark, heartwood, flower, fruit and leaf or plant exudates. These medicinal compounds

can be separate by different processes. The most common process is extraction. The

process or extraction is the separation of the required constituents from plant

materials by using a solvent. In the case of medicinal plants, the extraction procedure

can be divided into two categories.

a) Where it is sufficient to achieve within set limits equilibrium of concentration

between drug components and the solution. Example is Tea, Tinctures, Decoction etc.

b) Where it is necessary to extract the drug to exhaustion, means until all solvent

extractable are removed by the solvent.

Both the above methods are employed depending on the requirement in industry but

the latter method is mostly used. In all industrial procedures, the raw material is pre-

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treated with solvent outside the extract or before changing the latter. This prevents

sudden bulk volume changes which are the main cause of channelling during

extraction and facilitates the breaking up of the cell walls to release the

extractable. To facilitate the extraction, the solvent should diffuse inside the cell

and the substance must be sufficiently soluble in the solvent. To complete the

extraction ideal solvent is that one who is most selective, has the best capacity for

extraction and is compatible with the properties of the material to be extracted.

These parameters are predetermined experimentally. The availability and cost of the

solvent are also taken into account. Alcohol ( widely used), because of its great

extractive power it is often the least selective, in that it extracts all soluble

constituents. Alcohol in various ratios is used to reduce selectivity. The ideal

alcohol ratio for woody or bark material is 75%. For leafy material, it should often

less than 50% thus avoiding extraction of the chlorophyll which makes purification

difficult.

Some componants such as alkaloids are soluble in acid, their extraction is facilitated

by adjusting the pH in the acidic range. The alkaloids can be extracted easily with

hydrocarbons after they have been released from combination with organic acids by

grinding with alkali. It is first ground with moist calcium oxide and extracted with

chloroform. A large number of alkaloids can be also extracted directly with aqueous

acids, inorganic or organic acids, and the alkalised extracts counter extracted with

hydrocarbons or other nonpolar solvents.

process used for extraction with solvents usually comprise an extraction vessel with

a heating jacket for steam heating or fitted with electrical devices, a condenser in

reflux position, a solvent reservoir, a facility to convert to reboiler position or a

separate reboiler and a short column for solvent recovery. Sometimes, sophisticated

and costly equipment like the Carousel or the Inoxa extractor is employed.

For the manufacture of standardised extracts and phytochemicals, much

technology is available and there are many extracts already in the international market

in the form of drugs. Drug such as an extract of Centella asiatica can be

manufactured as an extract containing a standard quantity of asiaticoside. Similarly

for senna a standardised extract of which, containing a standard quantity of

sennoside-A and sennoside-B could easily produced with equipment that is designed

and constructed in most developing countries.

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The development and promotion of processing of medicinal and aromatic plants have

gained momentum recently in many developing countries. Green consumerism and

resurgence of interest for plant based products, liberalised and free market

economy, by increasing awareness about biodiversity conservation and right use of

natural resources coupled with poor socio-economic conditions of native populations

are ground realities for planning and harnessing the low-cost and purpose oriented

process technologies.

1.5 FORMULATION AND INDUSTRIAL UTILIZATION28-34

Medicinal plants are used as raw materials for extraction of active constituents in pure

form (eg. alkaloids like quinine and quinidine from cinchona bark, emetine from

ipecacuanha root, glycosides from digitalis leaves, sennosides from senna

leaves), as precursors for synthetic vitamins or steroids, and as preparations for

herbal and indigenous medicines. Products such as ginseng, valerian and liquorice

roots are part of the herbal and health food market, as well as the food flavours,

fragrance and cosmetic industries. Certain plant products are industrially exploited

like liquorice in confectionery and tobacco, papaine as meat tenderiser, quinine as

soft drink tonic and cinchona as wine flavour. A large quantity of medicinal plant

material is used in the preparation of herbal and medicinal teas, eg. chamomile.

These herbal and food uses are of great importance, also to the exporters from

developing countries. Hundreds of medicinal plants are items of commerce, however

relatively small countries are used in formulated herbal remedies.

Several formulations like herbal teas, extracts, decoctions, infusions, tinctures, etc are

prepared from medicinal plants.

Herbal teas, Herbal remedies: herbal tea or infusion mixtures are mixture of un

ground or suitably ground medicinal plants to which drug plant extracts,

ethereal oils or medicinal substances can be added. Infusion mixtures should be

as homogenous as possible.

1.6 DRUG EXTRACTS: They are preparations obtained by extracting drugs of a

certain particle size with suitable extraction agents (menstrua). The extract obtained

after separation of the liquid from the drug residue is called miscella. It may already

represent the final liquid doses form called as fluid extract, or be used as an

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intermediary product which is to be further processed as quickly as possible.

1.6.1 Aqueous drug extracts: The following degrees of comminution are used for the

extract depending on the type of plant parts. Leaves, flowers and herbs shredded

(4000mm); woods, barks and roots shredded (2800mm); fruits and seeds

(2000mm). Alkaloid containing drugs powdered (700mm).

Decoctions: The drug in the prescribed comminution is put in to water at a

temperature above 90 C. The container is suspended in a water bath and

maintained at this temperature for 30 minutes, with repeated stirring. The mixture is

then strained while still hot.

Infusions: One part of the comminuted drug is kneaded several times in a mortar with

3-5 parts of water and left to stand for 15 minutes. The rest of the boiling water is then

poured on to the mixture, which is suspended in a container in a water bath and

kept for 5 minutes, with repeated stirring at a temperature above 90 C. The mixture

is covered and left to stand until cool.

Macerates: The comminuted drug is left to stand, with occasional stirring, for 30

minutes after the required quantity of water has been poured on to it at room

temperature. The extract is then strained and made up to the prescribed weight with

rinsings.

Tinctures: Tinctures are extracts from drug plants prepared with ethanol of

varying concentration, ether or mixtures of these, perhaps with certain additives, in

such a way that one part of drug is extracted with more than two parts, but at most

ten parts, of extraction liquid.

1.6.2 Fluid extracts: Like tinctures, they are liquid preparations, the difference being

that they are more concentrated.

1.6.3 Dry extracts: They are usually very hygroscopic and should therefore be

ground and mixed under conditions which exclude moisture as much as possible.

Intermediate and end product must also be stored under dry conditions.

There are also liquid, semisolid, solid and controlled release formulations or

preparations. The other dose forms are injections, implants, ocular preparations,

inhalations and transdermal systems. Liquid formulations may be solutions,

emulsions, colloids or suspensions in the increasing order of particle size. They

may be intended for administration parenterally, orally or topically including

administration into body cavities. Homogeneity for the formulations is very important,

Introducion 11

particularly where the active ingredient is present in lower concentration.

1.7 PHYTOCHEMICALS35-36

Phytochemicals are non-nutritive plant chemicals that have protective or disease

preventive properties. There are more than thousand known phytochemicals. It is

well-known that plant produces these chemicals to protect itself but recent research

demonstrates that they can protect humans against diseases. Some of the well-known

phytochemicals are lycopene in tomatoes, isoflavones in soy and flavonoids in fruits.

They are not essential nutrients and are not required by the human body for sustaining

life.

The different phytochemicals are as follows:-

• Volatile oils

• Alkaloids

• Glycosides

• Flavonoids

• Tannins and Polyphenolic compounds

• Carbohydrates

• Proteins

• Fixed oils and Fats

• Terpenoids

Volatile oils

The essential oil is a concentrated, hydrophobic liquid containing volatile odour

compounds from plants. Volatile oils are also known as essential or ethereal oils, or

simply as the oil of the plant from which they were extracted, such as oil of clove. Oil

is necessary or essential in the sense that it carries a distinctive scent, or essence, of

the plant. These oils do not as a group needs to have any specific chemical properties

in common, beyond conveying characteristic fragrances. They are not to be confused

with essential fatty acids.

Essential oils are generally extracted by distillation. Other processes include

expression, or solvent extraction. They are used in perfumes, cosmetics and bath

products, for flavouring food and drink, and for scenting incense and household

cleaning products

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Various essential oils have been used medicinally at different periods in history.

Medical application proposed by those who sell medicinal oils range from skin

treatments to remedies for cancer, and are often based on historical use of these oils

for these purposes. Such claims are now subject to regulation in most countries, and

have grown vaguer to stay within these regulations.

Interest in essential oils has been recorded in recent decades with the popularity of

aromatherapy, a branch of alternative medicine which claims that the specific odour

carried by essential oils have curative effects. Oils are volatilized or diluted in carrier

oil and used in massage, diffused in the air by a nebulizer or by heating over a candle

flame, or burned as incense.

Alkaloids

Alkaloids are naturally occurring chemical compounds containing basic nitrogen

atoms. The name derives from the word alkaline and was used to describe any

including bacteria, fungi, plants, and animals and is part of the group of natural

products (also called secondary metabolites). Many alkaloids can be purified from

crude extracts by acid-base extraction. Many alkaloids are toxic to other organisms.

They often have pharmacological effects and are used as medications, as recreational

drugs, or in entheogenic rituals. Examples are the local anesthetic and stimulant

cocaine, the stimulant caffeine, nicotine, the analgesic morphine, or the antimalarial

drug quinine. Some alkaloids have a bitter taste.

Saponin Glycosides

Saponins are a class of chemical compounds, one of many secondary metabolites

found in natural sources, with Saponins found in particular abundance in various plant

species. Specifically, they are amphipathic glycosides grouped phenomenological by

the soap-like foaming they produce when shaken in aqueous solutions, and

structurally by their being composed of one or more hydrophilic glycoside moieties

combined with a lipophilic triterpene derivative. A ready and therapeutically relevant

example is the cardio-active agent digoxin, from common foxglove.

In chemistry, glycosides are molecules in which a sugar is bound to a non-

carbohydrate moiety, usually a small organic molecule. Glycosides play numerous

important roles in living organisms. Many plants store chemicals in the form of

inactive glycosides; which can be activated by enzyme hydrolysis. This causes the

sugar part to be broken off, making the chemical available for use. Many such plant

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glycosides are used as medications. In animals (including humans), poisons are often

bound to sugar molecules as part of their elimination from the body.

Formally, a glycoside is any molecule in which a sugar group is bonded through its

anomeric carbon to another group via a glycosidic bond. Glycosides can be linked by

an O- (an O-glycoside), N- (a glycosylamine), S-(a thioglycoside) or C- (a C-glycosyl)

glycosidic bond. The given definition is the one used by IUPAC. Many authors

require in addition that the sugar be bonded to a non-sugar for the molecule to qualify

as a glycoside, thus excluding polysaccharides. The sugar group is then known as the

glycone and the non-sugar group as the aglycone or genin part of the glycoside. The

glycone can consist of a single sugar group (monosaccharide) or several sugar groups

(oligosaccharide).

Anthraquinone Glycosides

Anthraquinone (9, 10-dioxoanthracene) is an aromatic organic compound. It is a

derivative of anthracene. It has the appearance of yellow or light gray to gray-green

solid crystalline powder.6

Its other names are 9, 10-anthracenedione, anthradione, 9, 10-anthrachinon,

anthracene-9, 10-quinone, 9, 10-dihydro-9, 10-dioxoanthracene.

Cyanogenic Glycosides

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In this glycoside, the aglycone contains a cyanide group, and the glycoside can release

the poisonous hydrogen cyanide if acted upon by some enzyme. They are

stored in the vacuole but if the plant is attacked they are released and become

activated by enzymes in the cytoplasm. These remove the sugar part of the

molecule and release toxic hydrogen cyanide. Storing them in inactive forms

in the cytoplasm prevents them from damaging the plant under normal

conditions. An example of these is amygdaline from almonds. They can also

be found in the fruits (and wilting leaves) of the rose family (including

cherries, apples, plums, almonds, peaches, apricots, raspberries, and

crabapples). Cassava, an important food plant in Africa and South America,

contains Cyanogenic glycosides and therefore has to be washed and ground

under running water prior to consumption. Sorghum (Sorghum bicolour)

expresses Cyanogenic glycosides in its roots and thus is resistant to pests

such as rootworms (Diabrotica spp.) that plague its cousin maize (Zea mays

L.). Some Cyanogenic glycosides may have anti-cancer properties. A recent

study may also show that increasing CO2 levels, caused by anthropogenic

emissions, may result in much higher levels of Cyanogenic glycoside

production in Sorghum and Cassava plants, making them highly toxic and

inconsumable. A doubling of CO2 concentration was found to double the

concentration of Cyanogenic glycosides in the leaves.

Flavonoids

Flavonoids (or bioflavonoid), also collectively known as Vitamin P and citrin, are a

class of plant secondary metabolites. According to the IUPAC nomenclature,

they can be classified into:

• Flavonoids, derived from 2-phenylchromen-4-one (2-phenyl-1, 4-

benzopyrone) structure (examples: quercetin, rutin). • Isoflavonoids, derived from 3-phenylchromen-4-one (3-phenyl-1, 4-benzopyrone)

structure • Neoflavonoids, derived from 4-phenylcoumarine (4-phenyl-1, 2-benzopyrone)

structure.

The three flavonoids classes above are all ketone-containing compounds, and as such,

are flavonoids and flavonols. This class was the first to be termed "bioflavonoid." The

terms flavonoids and bioflavonoid have also been more loosely used to describe non-

ketone polyhydroxy polyphenol compounds which are more specifically termed

Introducion 15

flavonoids, flavan-3-ols, or catechins (although catechins are actually a subgroup of

flavonoids). Flavonoids (both flavonols and flavonols) are most commonly known for

their antioxidant activity.

Flavonoids (specifically flavonoids such as the catechins) are "the most common

group of Polyphenolic compounds in the human diet and are found ubiquitously in

plants". Flavonols, the original bioflavonoid such as quercetin, are also found

ubiquitously, but in lesser quantities. Both sets of compounds have evidence of health-

modulating effects in animals which eat them.

Tannins and polyphenolic compounds

Tannins are astringent, bitter plant polyphenol that either bind and precipitate or

shrink proteins. The astringency from the tannins is what causes the dry and puckery

feeling in the mouth following the consumption of unripened fruit or red wine

Likewise, the destruction or modification of tannins with time plays an important role

in the ripening of fruit and the aging of wine.

The term tannin (from tanna, an Old High German word for oak or fir tree) refers to

the use of wood tannins from oak in tanning animal hides into leather; however, the

term is widely applied to any large Polyphenolic compound containing sufficient

hydroxyls and other suitable groups (such as carbonyls) to form strong complexes

with proteins and other macromolecules. The compounds are widely distributed in

many species of plants, where they play a role in protection from predation and

perhaps also in growth regulation.Tannins have molecular weights ranging from 500

to over 9,000. Tannins are incompatible with alkalis, gelatin, heavy metals, iron, lime

water, metallic salts, strong oxidizing agents and zinc sulfate.

Tannins are distributed in species throughout the plant kingdom. They are commonly

found in both gymnosperms as well as angiosperms. Histological tannins are mainly

physically located in the vacuoles or surface wax of plants. These storage sites keep

tannins active against plant predators, but also keep some tannin from affecting plant

metabolism while the plant tissue is alive; it is only after cell breakdown and death

that the tannins are active in metabolic effects.

Tannins are found in leaf, bud, seed, root, and stem tissues. An example of the

location of the tannins in stem tissue is that they are often found in the growth areas of

trees, such as the secondary phloem and xylem and the layer between the cortex and

epidermis. Tannins may help regulate the growth of these tissues. They are also found

Introducion 16

in the heartwood of conifers and may play a role in inhibiting microbial activity, thus

resulting in the natural durability of the wood. There may be a loss in the

bioavailability of still other tannins in plants due to birds, pests, and other pathogens.

The leaching of tannins from the decaying leaves of vegetation adjoining a stream

may produce what is known as a black water river.

Hydrolysable tannins

At the center of a hydrolysable tannin molecule, there is a carbohydrate (usually D-

glucose). The hydroxyl groups of the carbohydrate are partially or totally esterifies

with phenol groups such as gallic acid (in gallotannins) or ellagic acid (in

elligitannins). Hydrolysable tannins are hydrolyzed by weak acids or weak bases to

produce carbohydrate and phenol acids.

Examples of gallotannins are the gallic acid esters of glucose in tannic acid

(C76H52O46), found in the leaves and bark of many plant species.

Condensed tannins

Condensed tannins, also known as Proanthocyanidins, are polymers of 2 to 50 (or

more) flavonoids units that are joined by carbon-carbon bonds, which are not

susceptible to being cleaved by hydrolysis. While hydrolysable tannins and most

condensed tannins are water soluble, some very large condensed tannins are insoluble.

Condensed tannins from Lithocarpus glaber leaves have been analyzed through acid-

catalyzed degradation in the presence of cysteamin and have a potent free radical

scavenging activity.

Carbohydrates

Carbohydrates or saccharine are the most abundant of the four major classes of

bimolecular. They fill numerous roles in living things, such as the storage and

transport of energy (e.g., starch, glycogen) and structural components (e.g., cellulose

in plants and chitin in animals). In addition, carbohydrates and their derivatives play

major roles in the working process of the immune system, fertilization, pathogenesis,

blood clotting, and development.

Carbohydrates are simple organic compounds that are aldehydes or ketone with many

hydroxyl groups added, usually one on each carbon atom that is not part of the

aldehydes or ketone functional group. The basic carbohydrate units are called

monosaccharide; examples are glucose, galactose, and fructose. The general

stoichiometric formula of an unmodified monosaccharide is (C·H2O) n, where n is any

Introducion 17

number of three or greater; however, not all carbohydrates conform to this precise

stoichiometric definition (e.g., uronic acids, deoxy-sugars such as fructose), nor are all

chemicals that do conform to this definition automatically classified as carbohydrates.

Monosaccharide can be linked together into what are called polysaccharides (or

oligosaccharides) in a large variety of ways. Many carbohydrates contain one or more

modified monosaccharide units that have had one or more groups replaced or

removed. For example, deoxyribose, a component of DNA, is a modified version of

ribose; chitin is composed of repeating units of N-acetyl glucosamine, a nitrogen-

containing form of glucose.

While the scientific nomenclature of carbohydrates is complex, the names of

carbohydrates very often end in the suffix -ose. Glycoinformatics is the specialized

field of study that deals with the specific and unique bioinformatics of carbohydrates.

Proteins

Proteins (also known as polypeptides) are organic compounds made of amino acids

arranged in a linear chain and folded into a globular form. The amino acids in a

polymer chain are joined together by the peptide bonds between the carboxyl and

amino groups of adjacent amino acid residues. The sequence of amino acids in a

protein is defined by the sequence of a gene, which is encoded in the genetic code. In

general, the genetic code specifies 20 standard amino acids; however, in certain

organisms the genetic code can include selenocysteine and in certain archaea

pyrrolysine. Shortly after or even during synthesis, the residues in a protein are often

chemically modified by post-translational modification, which alter the physical and

chemical properties, folding, stability, activity, and ultimately, the function of the

proteins. Proteins can also work together to achieve a particular function, and they

often associate to form stable complexes.

Like other biological macromolecules such as polysaccharides and nucleic acids,

proteins are essential parts of organisms and participate in virtually every process

within cells. Many proteins are enzymes that catalyze biochemical reactions and are

vital to metabolism. Proteins also have structural or mechanical functions, such as

actin and myosin in muscle and the proteins in the cytoskeleton, which form a system

of scaffolding that maintains cell shape. Other proteins are important in cell signaling,

immune responses, cell adhesion, and the cell cycle. Proteins are also necessary in

animals' diets, since animals cannot synthesize all the amino acids they need and must

Introducion 18

obtain essential amino acids from food. Through the process of digestion, animals

break down ingested protein into free amino acids that are then used in metabolism.

Proteins were first described and named by the Swedish chemist Jones Jacob

Berzelius in 1838; however, the central role of proteins in living organisms was not

fully appreciated until 1926, when James B. Sumner showed that the enzyme urease

was a protein. The first protein to be sequenced was insulin, by Frederick Sanger, who

won the Nobel Prize for this achievement in 1958. The first protein structures to be

solved were hemoglobin and myoglobin, by Max Perutz and Sir John Cowdery

Kendrew, respectively, in 1958. The three-dimensional structures of both proteins

were first determined by x-ray diffraction analysis; Perutz and Kendrew shared the

1962 Nobel Prize in Chemistry for these discoveries. Proteins may be purified from

other cellular components using a variety of techniques such as ultracentrifugation,

precipitation, electrophoresis, and chromatography; the advent of genetic engineering

has made possible a number of methods to facilitate purification. Methods commonly

used to study protein structure and function includes immunohistochemistry, site-

directed mutagenesis, and mass spectrometry.

Fixed oil and Fats

Fats consist of a wide group of compounds that are generally soluble in organic

solvents and largely insoluble in water. Chemically, fats are generally triesters of

glycerol and fatty acids. Fats may be either solid or liquid at normal room

temperature, depending on their structure and composition. Although the words "oils",

"fats", and "lipids" are all used to refer to fats, "oils" is usually used to refer to fats

that are liquids at normal room temperature, while "fats" is usually used to refer to

fats that are solids at normal room temperature. "Lipids" is used to refer to both liquid

and solid fats, along with other related substances. The word "oil" is used for any

substance that does not mix with water and has a greasy feel, such as petroleum (or

crude oil) and heating oil, regardless of its chemical structure.

Fats form a category of lipid, distinguished from other lipids by their chemical

structure and physical properties. This category of molecules is important for many

forms of life, serving both structural and metabolic functions. They are an important

part of the diet of most heterotrophs (including humans). Fats or lipids are broken

down in the body by enzymes called lipases produced in the pancreas.

Introducion 19

Examples of edible animal fats are lard (pig fat), fish oil, and butter or ghee. They are

obtained from fats in the milk, meat and under the skin of the animal. Examples of

edible plant fats are peanut, soya bean, sunflower, sesame, coconut, olive, and

vegetable oils. Margarine and vegetable shortening, which can be derived from the

above oils, are used mainly for baking. These examples of fats can be categorized into

saturated fats and unsaturated fats.

Table 1.1: Structural features and activities of various phytochemicals from

plants37

Phytochemicals Structural features Example Activities

Phenols and

Polyphenols

C3 side chain, - OH

groups, phenol ring

Catechol,

Epicatechin,

Cinnamic acid

Antimicrobial,

Anthelmintic,

Antidiarrhoeal

Quinones Aromatic rings, two

ketone substitutions

Hypericin Antimicrobial

Flavones

Flavonoids

Flavonols

Phenolic structure, one

carbonyl group

Hydroxylated phenols,

C6-C3 unit linked to an

aromatic ring

Flavones + 3-hydroxyl

Abyssinone,

Chrysin,

Quercetin, Rutin

Totarol

Antimicrobial

Antidiarrhoeal

Tannins Polymeric phenols (Mol.

Wt. 500-3000)

Ellagitannin Antimicrobial,

Anthelmintic,

Coumarins Phenols made of fused

benzene and α- pyrone

rings

Warfarin

Antimicrobial

Terpenoids and

essential oils

Acetate units + fatty

acids,extensive

branching and cyclised

Capsaicin Antimicrobial

Antidiarrhoeal

Alkaloids Heterocyclic nitrogen

compounds

Berberine, Piperine,

Palmatine,

Tetrahydropalmatine

Antimicrobial,

Anthelmintic,

Antidiarrhoea

Introducion 20

Lectins and

Polypeptides

Proteins Mannose-specific

agglutinin, Fabatin

Antimicrobial

Glycosides Sugar + non

carbohydrate moiety

Amygdalin Antidiarrhoeal

Saponins Amphipathic glycosides Vina-ginsenosides-

R5 and -R6

Antidiarrhoeal

1.8 EXTRACTION38-40

The commonly employed technique for separation of active substance from crude

drug is called as ‘Extraction’ which involves the use of different solvents. The plant

material used for extraction should be properly authenticated or identified. The choice

of the plant material for extraction depends upon its nature and the components

required being isolated. The dried powdered plant material is commonly used for

extraction. The solvent used for extraction is called menstrum and the residue is

known as marc.

Methods of extraction

There are various methods of extraction. Some of them are described below:

Maceration

The word maceration means softening. It is the simplest method of crude drug

extraction and was official in I.P.1966. The process consists of keeping the crude drug

in intimate contact with whole menstrum in a closed vessel with occasional shaking

for seven days, straining, pressing the marc, mixing the liquids and finally clarifying

by subsidence or filtration. The process may take up to 14 days in some cases for

complete extraction. The drug: menstrum ratio should be 1: 10.

Infusion

Infusions are usually prepared from vegetable drugs containing water soluble and

easily extractable principles. The process consisted of moistening the drug with water,

macerating it with boiling water, straining and making up the volume.

Digestion

This is a modified maceration process in which extraction is accomplished at a higher

temperature at which the active ingredients are not adversely affected. Use of higher

temperature provides for enhanced solvent action of menstrum and constant

Introducion 21

mechanical agitation of the system accelerates establishment of equilibrium in a short

time.

Decoction

Decoction is also employed for extracting vegetable drugs containing water-soluble

and heat-soluble constitutes. The process consisted of boiling the drug with water,

cooling, expressing, straining liquid and finally make up the volume.

Percolation

Percolation is extraction process in which granulated or powdered drug is deprived of

its constant by the descent of a suitable menstrum through it. In Greek, the word

‘percolate’ means ‘to pass through’. The process implies a slow passage of menstrum

under the influence of gravity through a column of the drug. During this movement,

the menstrum goes on extracting the drug particle layer wise, it being replaced by

other layers above as it moves downwards.

Ultrasonic extraction

The speed of drug extraction is enhanced by application of ultrasonic vibrations. The

mixture of the drug and the menstrum is subjected to ultrasonic waves of 20 to 450

kilocycles/second followed by extraction in a soxhlet extractor. The treatment with

ultrasonic vibrations provides rapid and superior extraction.

Successive solvent extraction

Soxhlet extractor

A Soxhlet extractor is a piece of laboratory apparatus invented in 1879 by Franz von

Soxhlet. It was originally designed for the extraction of a lipid from a solid material.

However, a Soxhlet extractor is not limited to the extraction of lipids. Typically, a

Soxhlet extraction is only required where the desired compound has a limited

solubility in a solvent, and the impurity is insoluble in that solvent. If the desired

compound has a high solubility in a solvent then a simple filtration can be used to

separate the compound from the insoluble substance.

Normally a solid material containing some of the desired compound is placed inside a

thimble made from thick filter paper, which is loaded into the main chamber of the

Soxhlet extractor. The Soxhlet extractor is placed onto a flask containing the

extraction solvent. The Soxhlet is then equipped with a condenser.The solvent is

heated to reflux. The solvent vapour travels up a distillation arm, and floods into the

Introducion 22

chamber housing the thimble of solid. The condenser ensures that any solvent vapour

cools, and drips back down into the chamber housing the solid material.

The chamber containing the solid material slowly fills with warm solvent. Some of

the desired compound will then dissolve in the warm solvent. When the Soxhlet

chamber is almost full, the chamber is automatically emptied by a siphon side arm,

with the solvent running back down to the distillation flask. This cycle may be

allowed to repeat many times, over hours or days.

During each cycle, a portion of the non-volatile compound dissolves in the solvent.

After many cycles the desired compound is concentrated in the distillation flask. The

advantage of this system is that instead of many portions of warm solvent being

passed through the sample, just one batch of solvent is recycled.

After extraction the solvent is removed, typically by means of a rotary evaporator,

yielding the extracted compound. The non-soluble portion of the extracted solid

remains in the thimble, and is usually discarded.

1.9 PRELIMINARY PHYTOCHEMICAL SCREENING41-44

Preliminary Phytochemical Screening is a process of tracing plant constituents. There

are general plant constituents that can be performed with a standard test. The plant is a

biosynthetic laboratory, not only for chemical compounds such as carbohydrates,

proteins and lipids that are food by man, but also for a multitude of compounds like

glycosides, alkaloids, volatile oils, tannins etc. that exert a physiological and

therapeutic effect. The compounds that are responsible for medicinal property of the

drug are secondary metabolites. A systematic study of crude drug embraces, through

consideration of primary and secondary metabolites derived as a result of plant

metabolism. The plant material is subject to dried to preliminary phytochemical

screening for the detection of various plant constituents. Chemical test evaluation is a

method by which we can determine the different constituent present in the drug, so

different chemical test will be performed. Plant-derived substances have recently

become of great interest owing to their versatile applications.

1.9.1 Choice of solvents

Successful determination of biologically active compounds from plant material

is largely dependent on the type of solvent used in the extraction procedure.

Properties of a good solvent in plant extractions includes, low toxicity, ease of

Introducion 23

evaporation at low heat, promotion of rapid physiologic absorption of the extract,

preservative action, inability to cause the extract to complex or dissociate. The

factors affecting the choice of solvent are quantity of phytochemicals to be extracted,

rate of extraction, diversity of different compounds extracted, diversity of

inhibitory compounds extracted, ease of subsequent handling of the extracts, toxicity

of the solvent in the bioassay process, potential health hazard of the extractants. The

choice of solvent is influenced by what is intended with the extract. Since the end

product will contain traces of residual solvent, the solvent should be non- toxic and

should not interfere with the bioassay. The choice will also depend on the targeted

compounds to be extracted.

Table 1.2: Solvents used for active component extraction

Water Ethanol Methanol Chlorofor

m

Ether Acetone

Anthocyanins Tannins Anthocyanins Terpenoids Alkaloids Phenol

Starches Polyphenols Terpenoids Flavonoids Terpenoids Flavonols

Tannins Polyacetylen Saponins Coumarins

Saponins Flavonol Tannins Fatty Acids

Terpenoids Terpenoids Xanthoxyllines

Polypeptides Sterols Totarol

Lectins Alkaloids Quassinoids

Lactones

Flavones

Phenones

Polyphenols

1.9.2 Phytochemical Screening: Phytochemical examinations were carried out for all

the extracts as per the standard methods.

Detection of Alkaloids:

Dragendroff’s reagent: Reddish brown precipitate

Wagner;s reagent: Reddish brown precipitate

Mayer’s reagent: Cream colour precipitate

Hager’s reagent: Yellow precipitate

Detection of Carbohydrates:

Molisch’s Test: Violet ring

Introducion 24

Benedict’s Test: Orange red precipitate

Fehling’s Test: Red precipitate

Detection of Glycosides:

Modified Borntrager’s Test: Rose-Pink colour

Legal’s Test: Pink to Blood red colour

Detection of Fixed oils and Fats

Spot Test: Appearance of oil stain

Soap Formation Test: Formation of soap

Detection of Fenolic compounds and Tannins

FeCl3 Solution Test: Violet colour.

Gelatin Test: White precipitate

Lead Acetate Test: White precipitate

Detection of Proteins and Amino acids

Xanthoproteic Test: Yellow colour

Ninhydrin Test: Blue colour

Detection of Flavonoids

Alkaline Reagent Test: Yellow colour

Lead Acetate Test: Yellow colour

Detection of Steroids and Triterpenoides

Salkowski’s Test: Golden Yellow colour

Libermann Burchard’s Test: Brown ring

Detection of Mucilage and Gums

With Absolute Alcohol: Precipitate and examined for swelling property

Detection of Waxes

Alcoholic Alkali Solution Test: waxes get saponified.

Detection of Phenols

Ferric Chloride Test: Bluish black colour.

1.10 ANALGESIC45-57

The term analgesic is known any member of the group of drugs which is used to

relieve from pain means achieve analgesia. The word analgesic derives from Greek an

maens “without" and algos means "pain". These drugs act in various ways on the

nervous and central peripheral systems. These drugs include many category like

Introducion 25

NSAIDs (non-steroidal anti-inflammatory drugs) such as the Acetic Acid derivatives,

Salicylic Acid derivatives and opioid analgesics drugs such as morphine and opium.

They can be distinct from anaesthetics in the manner of reversibly eliminate

sensation.

Pain is defined as neuralgia, an unpleasant sensory experience associated with tissue

damage. The nerves in our body send a response to the brain which allows the body to

feel pain. Pain can chronic or acute and can come and go in repeated manner. All of us

have suffered from pain in once or many times whether it can be from injury or not.

Sometimes we can ignore pain but many times we may need something to help us

along.

There are many herbs in the world that are very useful and effective for relief of pain.

Many of them are safe and effective for everyone but some should be avoided during

pregnancy or while nursing. Herbal medicines definitely have outstanding analgesic

properties, in addition anti-inflammatory and anti-spasmodic functions also found.

However, even though herbs and pharmaceutical drugs have many overlapping

functions, they are not directly interchangeable or analogs of each other. The

therapeutic effectiveness of herbal formulas is dependent on accurate diagnosis and

careful prescription. When analgesic herbs used properly, it can be powerful

alternatives to drug of choice for pain management.

The use of herbal medicine in the world has increased dramatically in recent years.

These products are not regulated by the Food and Drug Administration with the same

scrutiny as conventional drugs. Patients who use herbal supplements often do so in

conjunction with conventional drugs.

Being a natural pain relief herb, any type of analgesic herb has the advantage of not

producing any side effects as is the case with other chemically produced pain relief

medicine. There are many analgesic herbs that are typically known as joint herbs for

their analgesic properties of giving relief from joint pains like those felt in arthritis,

neck and back pain, or tendonitis. In fact, these therapeutic herbs are anti-

inflammatory herbs and treat the pain conditions that result from inflammation of

joints.

The choice of drug analgesic is also determined by the type of pain means for

neuropathic pain and traditional analgesics are less effective and there is often benefit

Introducion 26

from classes of drugs that are not normally considered analgesics category, such as

antidepressants and antiepileptic.

Treatment

Paracetamol and NSAIDs

The exact mechanism of action of paracetamol/acetaminophen is uncertain, but it

appears to be acting centrally rather than peripherally (in the brain rather than in nerve

endings). Aspirin and the other non-steroidal anti-inflammatory drugs (NSAIDs)

inhibit cyclooxygenases, leading to a decrease in prostaglandin production. This

reduces pain and also inflammation (in contrast to paracetamol and the opioids).

Paracetamol has few side effects and is regarded as safe, although intake above the

recommended dose can lead to liver damage, which can be severe and life-

threatening, and occasionally kidney damage. NSAIDs predispose to peptic ulcers,

renal failure, allergic reactions, and occasionally hearing loss, and they can increase

the risk of hemorrhage by affecting platelet function. The use of aspirin in children

under 16 suffering from viral illness has been linked to Reye's syndrome, a rare but

severe liver disorder.

COX-2 inhibitors

These drugs have been derived from NSAIDs. The cyclooxygenase enzyme inhibited

by NSAIDs was discovered to have at least 2 different versions: COX1 and COX2.

Research suggested that most of the adverse effects of NSAIDs were mediated by

blocking the COX1 (constitutive) enzyme, with the analgesic effects being mediated

by the COX2 (inducible) enzyme. The COX2 inhibitors were thus developed to

inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general).

These drugs (such as rofecoxib and celecoxib) are equally effective analgesics when

compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular.

However, post-launch data indicated increased risk of cardiac and cerebrovascular

events with these drugs; this is probably due to an imbalance in blood coagulation.

Rofecoxib (marketed as Vioxx) was subsequently withdrawn from the market. The

role for the remaining members of this class of drug is debated. The introduction of

the new IV pain medication, Ofirmev (IV acetaminophen) has been shown to improve

pain relief and reduce opioid consumption in the perioperative setting. Ofirmev does

not carry black box warnings for increased bleed risk and renal toxicity, which are

Introducion 27

warnings for some of the commonly prescribed NSAIDs. IV acetaminophen is the

most widely used IV analgesic in hospitals throughout Europe, where it has been

commercially available since 2002. The use of IV acetaminophen for surgical patients

is quickly becoming a standard of care in the United States.

Opiates and morphinomimetics

Morphine, the archetypal opioid, and various other substances (e.g. codeine,

oxycodone, hydrocodone, dihydromorphine, pethidine) all exert a similar influence on

the cerebral opioid receptor system. Buprenorphine is thought to be a partial agonist

of the opioid receptor, and tramadol is an opiate agonist with SNRI properties.

Tramadol is structurally closer to venlafaxine than to codeine and delivers analgesia

by not only delivering "opiate-like" effects (through mild agonism of the mu receptor)

but also by acting as a weak but fast-acting serotonin releasing agent and

norepinephrine reuptake inhibitor. Dosing of all opioids may be limited by opioid

toxicity (confusion, respiratory depression, myoclonic jerks and pinpoint pupils),

seizures (tramadol), but there is no dose ceiling in patients who accumulate tolerance.

Opioids, while very effective analgesics, may have some unpleasant side-effects.

Patients starting morphine may experience nausea and vomiting (generally relieved by

a short course of antiemetics such as phenergan). Pruritus (itching) may require

switching to a different opioid. Constipation occurs in almost all patients on opioids,

and laxatives (lactulose, macrogol-containing or co-danthramer) are typically co-

prescribed. When used appropriately, opioids and similar narcotic analgesics are

otherwise safe and effective, however risks such as addiction and the body becoming

used to the drug (tolerance) can occur. The effect of tolerance means that frequent use

of the drug may result in its diminished effect so, when safe to do so, the dosage may

need to be increased to maintain effectiveness. This may be of particular concern

regarding patients suffering with chronic pain.

Flupirtine

Flupirtine is a centrally acting K+ channel opener with weak NMDA antagonist

properties. It is used in Europe for moderate to strong pain and migraine and its

muscle relaxant properties. It has no anticholinergic properties and is believed be

devoid of any activity on dopamine, serotonin or histamine receptors. It is not

addictive and tolerance usually does not develop. However, tolerance may develop in

single cases.

Introducion 28

Specific agents

In patients with chronic or neuropathic pain, various other substances may have

analgesic properties. Tricyclic antidepressants, especially amitriptyline, have been

shown to improve pain in what appears to be a central manner. Nefopam is used in

Europe for pain relief with concurrent opioids. The exact mechanism of

carbamazepine, gabapentin and pregabalin is similarly unclear, but these

anticonvulsants are used to treat neuropathic pain with differing degrees of success.

Anticonvulsants are most commonly used for neuropathic pain as their mechanism of

action tends to inhibit pain sensation.

Specific forms and uses

Combinations

Analgesics are frequently used in combination, such as the paracetamol and codeine

preparations found in many non-prescription pain relievers. They can also be found in

combination with vasoconstrictor drugs such as pseudoephedrine for sinus-related

preparations, or with antihistamine drugs for allergy sufferers. While the use of

paracetamol, aspirin, ibuprofen, naproxen and other NSAIDS concurrently with weak

to mid-range opiates (up to about the hydrocodone level) has been said to show

beneficial synergistic effects by combating pain at multiple sites of action, several

combination analgesic products have been shown to have few efficacy benefits when

compared to similar doses of their individual components. Moreover, these

combination analgesics can often result in significant adverse events, including

accidental overdoses, most often due to confusion which arises from the multiple (and

often non-acting) components of these combinations.

Topical or systemic

Topical analgesia is generally recommended to avoid systemic side-effects. Painful

joints, for example, may be treated with an ibuprofen- or diclofenac-containing gel;

capsaicin also is used topically. Lidocaine, an anaesthetic, and steroids may be

injected into painful joints for longer-term pain relief. Lidocaine is also used for

painful mouth sores and to numb areas for dental work and minor medical procedures.

Psychotropic agents

Tetrahydrocannabinol (THC) and some other cannabinoids, either from the Cannabis

sativa plant or synthetic, have analgesic properties, although the use of cannabis

derivatives is currently illegal in many countries. A recent study finds that inhaled

Introducion 29

cannabis is effective in alleviating neuropathy and pain resulting from e.g. spinal

injury and multiple sclerosis. Other psychotropic analgesic agents include ketamine

(an NMDA receptor antagonist), clonidine and other α2-adrenoreceptor agonists, and

mexiletine and other local anaesthetic analogues.

Atypical, adjuvant analgesics & potentiators

Drugs which have been introduced for uses other than analgesics are also used in pain

management. Both first-generation (such as amitriptyline) and newer anti-depressants

(such as duloxetine) are used alongside NSAIDs and opioids for pain involving nerve

damage and similar problems. Other agents directly potentiate the effects of

analgesics, such as using hydroxyzine, promethazine, carisoprodol or tripelennamine

to increase the pain-killing ability of a given dose of opioid analgesic.

Adjuvant analgesics, also called atypical analgesics, include nefopam, orphenadrine,

pregabalin, gabapentin, cyclobenzaprine, scopolamine, and other drugs possessing

anticonvulsant, anticholinergic and/or antispasmodic properties, as well as many other

drugs with CNS actions. These drugs are used along with analgesics to modulate

and/or modify the action of opioids when used against pain, especially of neuropathic

origin.

Dextromethorphan has been noted to slow the development of tolerance to opioids

and exert additional analgesia by acting upon the NMDA receptors; some analgesics

such as methadone and ketobemidone and perhaps piritramide have intrinsic NMDA

action.

High-alcohol liquor, two forms of which were in the US Pharmacopoeia up until 1916

and in common use by physicians well into the 1930s, has been used in the past as an

agent for dulling pain, due to the CNS depressant effects of ethyl alcohol, a notable

example being the American Civil War. However, the ability of alcohol to relieve

severe pain is likely inferior to many analgesics used today (e.g. morphine, codeine).

As such, the idea of alcohol for analgesia is generally considered a primitive practice

in virtually all industrialized countries today.

The use of adjuvant analgesics is an important and growing part of the pain-control

field and new discoveries are made practically every year. Many of these drugs

combat the side effects of opioid analgesics, an added bonus. For example,

antihistamines including orphenadrine combat the release of histamine caused by

many opioids. Stimulants such as methylphenidate, caffeine, ephedrine,

Introducion 30

dextroamphetamine, and cocaine work against heavy sedation and may elevate mood

in distressed patients as do the antidepressants. The use of medicinal cannabis remains

a debated issue.

1.11 INFLAMMATION58-61

Inflammation (Latin, īnflammō, "I ignite, set alight") is part of the complex biological

response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or

irritants.[1] Inflammation is a protective attempt by the organism to remove the

injurious stimuli and to initiate the healing process. Inflammation is not a synonym

for infection, even in cases where inflammation is caused by infection. Although

infection is caused by a microorganism, inflammation is one of the responses of the

organism to the pathogen. However, inflammation is a stereotyped response, and

therefore it is considered as a mechanism of innate immunity, as compared to adaptive

immunity, which is specific for each pathogen. Without inflammation, wounds and

infections would never heal. Similarly, progressive destruction of the tissue would

compromise the survival of the organism. However, chronic inflammation can also

lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid

arthritis, and even cancer (e.g., gallbladder carcinoma). It is for that reason that

inflammation is normally closely regulated by the body.

Inflammation can be classified as either acute or chronic. Acute inflammation is the

initial response of the body to harmful stimuli and is achieved by the increased

movement of plasma and leukocytes (especially granulocytes ) from the blood into the

injured tissues. A cascade of biochemical events propagates and matures the

inflammatory response, involving the local vascular system, the immune system, and

various cells within the injured tissue. Prolonged inflammation, known as chronic

inflammation, leads to a progressive shift in the type of cells present at the site of

inflammation and is characterized by simultaneous destruction and healing of the

tissue from the inflammatory process.

Causes

• Burns• Chemical irritants• Frostbite• Toxins• Infection by pathogens• Physical injury, blunt or penetrating

Introducion 31

• Immune reactions due to hypersensitivity• Ionizing radiation• Foreign bodies, including splinters, dirt and debris• Stress• Trauma

• The traditional names for signs of inflammation come from Latin:

• Dolor (pain)• Colour (heat)• Rubor (redness)• Tumor (swelling)• Functio laesa (loss of function)

The first four (classical signs) were described by Celsus (ca 30 BC–38 AD), while

loss of function was added later by Galen ] even though the attribution is disputed and

the origination of the fifth sign has also been ascribed to Thomas Sydenham and

Virchow.

Redness and heat are due to increased blood flow at body core temperature to the

inflamed site; swelling is caused by accumulation of fluid; pain is due to release of

chemicals that stimulate nerve endings. Loss of function has multiple causes.

These five signs appear when acute inflammation occurs on the body's surface,

whereas acute inflammation of internal organs may not result in the full set. Pain only

happens where the appropriate sensory nerve endings exist in the inflamed area—e.g.,

acute inflammation of the lung (pneumonia) does not cause pain unless the

inflammation involves the parietal pleura, which does have pain-sensitive nerve

endings.

Anti-inflammatory refers to the property of a substance or treatment that reduces

inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying

pain by reducing inflammation as opposed to opioids, which affect the central nervous

system.

Treatment

Steroids

Many steroids, to be specific glucocorticoids, reduce inflammation or swelling by

binding to glucocorticoid receptors. These drugs are often referred to as

corticosteroids.

Non-steroidal anti-inflammatory drugs

Introducion 32

Non-steroidal anti-inflammatory drugs (NSAIDs), alleviate pain by counteracting the

cyclooxygenase (COX) enzyme. On its own, COX enzyme synthesizes

prostaglandins, creating inflammation. In whole, the NSAIDs prevent the

prostaglandins from ever being synthesized, reducing or eliminating the pain.

Some common examples of NSAIDs are: aspirin, ibuprofen, and naproxen. The newer

specific COX-inhibitors - although, it is presumed, sharing a similar mode of action -

are not classified together with the traditional NSAIDs.

On the other hand, there are analgesics that are commonly associated with anti-

inflammatory drugs but that have no anti-inflammatory effects. An example is

paracetamol, called acetaminophen in the U.S. and sold under the brand name of

Tylenol. As opposed to NSAIDS, which reduce pain and inflammation by inhibiting

COX enzymes, paracetamol has recently been shown to block the reuptake of

endocannabinoids, which only reduces pain, likely explaining why it has minimal

effect on inflammation.

Long-term use of NSAIDs can cause gastric erosions, which can become stomach

ulcers and in extreme cases can cause severe haemorrhage, resulting in death. The risk

of death as a result of use of NSAIDs is 1 in 12,000 for adults aged 16–45. The risk

increases almost twentyfold for those over 75. Other dangers of NSAIDs are

exacerbating asthma and causing kidney damage. Apart from aspirin, prescription

and over-the-counter NSAIDs also increase the risk of myocardial infarction and

stroke.

Immune Selective Anti-Inflammatory Derivatives (ImSAIDs)

ImSAIDs are a class of peptides being developed by IMULAN BioTherapeutics,

LLC, which were discovered to have diverse biological properties, including anti-

inflammatory properties. ImSAIDs work by altering the activation and migration of

inflammatory cells, which are immune cells responsible for amplifying the

inflammatory response. The ImSAIDs represent a new category of anti-inflammatory

and are unrelated to steroid hormones or non-steroidal anti-inflammatories.

The ImSAIDs were discovered by scientists evaluating biological properties of the

submandibular gland and saliva. Early work in this area demonstrated that the

submandibular gland released a host of factors that regulate systemic inflammatory

responses and modulate systemic immune and inflammatory reactions. It is now well

accepted that the immune, nervous, and endocrine systems communicate and interact

Introducion 33

to control and modulate inflammation and tissue repair. One of the neuroendocrine

pathways, when activated, results in the release of immune-regulating peptides from

the submandibular gland upon neuronal stimulation from sympathetic nerves. This

pathway or communication is referred to as the cervical sympathetic trunk-

submandibular gland (CST-SMG) axis, a regulatory system that plays a role in the

systemic control of inflammation.

Early work in identifying factors that played a role in the CST-SMG axis lead to the

discovery of a seven amino acid peptide, called the submandibular gland peptide-T.

SGP-T was demonstrated to have biological activity and thermoregulatory properties

related to endotoxin exposure. SGP-T, an isolate of the submandibular gland,

demonstrated its immunoregulatory properties and potential role in modulating the

cervical sympathetic trunk-submandibular gland (CST-SMG) axis, and subsequently

was shown to play an important role in the control of inflammation.

One SGP-T derivative is a three-amino acid sequence shown to be a potent anti-

inflammatory molecule with systemic effects. This three-amino acid peptide is

phenylalanine-glutamine-glycine (FEG) and its D-isomeric form (feG) have become

the foundation for the ImSAID category. Cellular Effects of feG: The cellular effects

of the ImSAIDs are characterized in a number of publications. feG and related

peptides are known to modulate leukocyte (white blood cells) activity by influencing

cell surface receptors to inhibit excessive activation and tissue infiltration.

One lead ImSAID, the tripeptide FEG (Phe-Glu-Gly) and its D-isomer feG are known

to alter leukocyte adhesion involving actions on αMβ2 integrin, and inhibit the

binding of CD16b (FCyRIII) antibody to human neutrophils. feG has also been shown

to decrease circulating neutrophil and eosinophil accumulation, decrease intracellular

oxidative activity, and reduce the expression of CD49d after antigen exposure.

Table 1.3: Plants with analgesic and anti inflammatory activity

Plant Family Part used Place DoseAbutilon indicum Malvaceae Fixed oil India 400 and 600 mg/kgAcacia ferruginea Fabaceae Stembark India 50 mg/kgAcacia nilotica Fabaceae od Saudi 500 mg/kgAchillea ageratum Asteraceae Dried aerial Spain 187 and 254 mg/kgAcicarpha Calyceraceae Dried aerial Peru 50 mcg/kgAconitum japonicum Ranunculaceae Dried root Japan 30 mg/kgAcorus calamus Araceae Rhizome, root India not statedAdansonia digitata Bombacaceae Dried fruit Sudan 400 and 800 mg/kgAfrormosia laxiflora Fabaceae Dried leaf Africa 0,5 mg/kg

Introducion 34

Agastache sinense Lamiaceae Dried root Taiwan 1,3 , 3,8mg/kgAlhagi maurorum Fabaceae Aerial parts Saudi 500 mg/kgAnchomanes Araceae Dried rhizome Nigeria 100 mg/kgAnnona squamosa Annonaceae Defatted seed India 250 mg/kgApium graveolens Apiaceae Dried seed Jordan 200 mg/kgAraujia sericifera Asclepiadaceae Dried fruit Spain 200 mg/kgAstragalus siculus Fabaceae Dried root Italy 0,5 mg/kgBaphia nitida Fabaceae Fresh leaf Nigeria 100 mg/kgBerlinia grandiflora Fabaceae Dried bark Nigeria 10 mg/kgBrassica rapa Brassicaceae Seed Saudi 500 mg/kgBuddleja cordata Buddlejaceae Dried leaf Mexico 25 and 100 mg/kg not Calotropis procera Asclepiadaceae Dried aerial Saudi 500 mg/kgCannabis sativa Cannabaceae Entire plant India 250 mg/kgCanthium Rubiaceae Aerial parts India not statedCarthamus Asteraceae Flowers Saudi 500 mg/kgCedrus deodara Pinaceae Wood India 100 mcg/kgCelastrus Celastraceae Dried flowersPakistan 300 mg/kgCentella asiatica Apiaceae Dried entire India 100 mg/kgChasmanthera Menispermacea Fresh leaf Nigeria 0,2 ml/kgChelidonium majus Papaveraceae Entire plant Austria 9,5 and 28 mg/kgChrozophora Euphorbiaceae aerialparts Egypt 500 mg/kgCinnamomum Lauraceae Dried bark Jordan 200 and 400 mg/kgCitrullus colocynthis Cucurbitaceae Aerial parts Saudi 500 mg/kgClematis chinensis Ranunculaceae Dried root Taiwan 6 and 12 mg/kgCleome viscose Capparidaceae Dried seed Jamaica 20 mg/kgClerodendrum Verbenaceae Entire plant India 500 mg/kgClitoria ternatea Fabaceae Dried aerial India 230 and 460 mg/kgCocculus pendulus Menispermacea Seed Saudi 500 mg/kgCommiphora Burseraceae Gun-resin Italy 10 ml/kgCordia francisci Boraginaceae Dried leaf Italy 5 ml/kgCordia martinicensis Boraginaceae Freeze-dried Italy 1 mg/kgCordia myxa Boraginaceae Leaf Italy 500 mg/kgCordia ulmifolia Boraginaceae Freeze-dried Italy 1 mg/kgCucumis trigonus Cucurbitaceae Dried fruit India 2,5 mg/kgCulcitium canascens Asteraceae Dried aerial Peru 2 mg/kgCuscuta chinensis Convolvulacea Dried entire India 1 mg/kgCyathea nilgirensis Cyatheaceae Aerial parts India 0,25 mg/kgCymbopogon Poaceae Entire plant Saudi 500 mg/kgCystoseira usneoides Cystoseiraceae Dried thallus Spain 6,25 mg/kgDesmodium Fabaceae Dried entire USSR not statedDioclea grandiflora Fabaceae rootbark Brazil 12,5 and 50 mg/kgDiodia scandens Rubiaceae Dried entire Nigeria 50 mg/kgDolichos falcatus Fabaceae Dried root China 5 mg/kgDucrosia ismaelis Apiaceae Essential oil Saudi 1 mg/kgEgletes viscosa Asteraceae Flower Brazil 400 mg/kgElaeagnus kologa Elaeagnaceae Aerial parts India not statedElaeocarpus Elaeocarpaceae Fruit India 100 mg/kgEriobotrya Rosaceae Aerial parts India not statedErvatamia coronaria Apocynaceae Dried stem Brazil 150 mg/kgEryngium foetidum Apiaceae Dried leaf D. 250 mg/kgEucaluptus Myrtaceae Dried leaf Jordan 100 mg/kgEuphorbia hirta Euphorbiaceae Dried entire New 20 and 141 mg/kg

Introducion 35

Fagraea racemosa Loganiaceae Fresh root Malaysia 3 mg/kgFicus glomerata Moraceae Dried leaf Africa 0.5 mg/kgFoeniculum vulgare Apiaceae Dried fruit Saudi 500 mg/kgGanoderma lucidum Ganodermatacefruitbody japan 100 and 300mg/kgGenista patens Fabaceae Dried leaf- Spain 200 mg/kgGlaucium flavum Papaveraceae Dried fruit- Spain 400 mg/kgHarpagophytum Pedaliaceae Driet root South 20 and 200 mg/kgHedera rhombea Araliaceae Dried leaf South 0,5 and 1 mg/kgHeracleum Apiaceae Dried root Taiwan 11 mg/kgHibiscus sabdariffa Malvaceae Calyx Saudi 500 mg/kgHimanthalia Himanthaliacea Dried thallus Spain 20; 40 and 100 mg/kgHimulus lupulus Cannabaceae Strobilus South 100 mg/kgHypericum Clusiaceae Dried aerial Turkey 125 and 250 mg/kgHypericum Clusiaceae Dried aerial Turkey 125 and 250 mg/kgInula crithmoides Asteraceae Dried aerial Spain 200 mg/kgIpomoea leari Convolvulacea Deffated seedIndia 60 and 90 mg/kgIrvingia gabonensis Simaroubaceae stembark Nigeria 500 mg/kgJuniperus oxycedrus Cupressaceae Dried leaf- Spain 200 mg/kgLaminaria Laminariaceae Dried thallus Spain 100 mg/kgLantana camara Verbenaceae Dried leaf Africa 0.5 mg/kgLawsonia inermis Lyrthraceae Leaf Saudi 500 mg/kgLedebouriella Apiaceae Entire plant China not statedLepidium sativum Brassicaceae Seed Saudi 500 mg/kgLeucas aspera Lamiaceae Dried entire India 50 and 400 mg/kgLeucojum aestivum Amaryllidaceae Dried bulb Turkey 500 mg/kgLigusticum sinense Apiaceae Dried root Taiwan 8,3 mg/kgLippia alba Verbenaceae Fresh leaf Brazil 1 mg/kgLippia geminata Verbenaceae Dried leaf Africa 0,5 mg/kgLuvunga scandens Rutaceae Fruit India 100 mg/kgclavatum Lycopodiaceae Dried aerial Taiwan 4,1 and 8,2 mg/kgLysimachia Primulaceae Dried aerial China 150 and 250 mg/kgMaesa ramentacea Myrsinaceae Dried aerial India not statedMelaleuca elliptica Myrtaceae Fresh aerial Egypt 0,36 mg/kgMelaleuca Myrtaceae Dried leaf Egypt 16.8 mg/kgMentha piperita Lamiaceae Dried leaf Jordan 400 mg/kgMikania cordata Asteraceae Root India 100 mg/kgMorinda citrifolia Rubiaceae Decorticated France 800 mg/kgMorus alba Moraceae Rootbark Japan 2 mg/kgMyrica nagi Myricaceae stembark India 250 mg/kgMyrtus communis Myrtaceae Dried leaf Iraq 150 mg/kgNepeta italica Lamiaceae Leaf essentialTurkey 0,03 mg/kgNeurolaena lobata Asteraceae Dried aerial Brazil 100 mg/kgNigella sativa Ranunculaceae Seed oil India 1 mg/kgNyctanthes arbor- Verbenaceae Shade dried India 2 mg/kgOcimum sanctum Lamiaceae Shade dried India 250 mg/kgOplopanax elatus Araliaceae Root China not statedOriganum onites Lamiaceae Essential oil Turkey 0,03 ml/kgPaeonia moutan Paeoniaceae Dried root South 200 mg/kgPanax ginseng Araliaceae Leaf Japan 400 mg/kgPanax ginseng Araliaceae Dried root India 50 mg/kgPanax eudoginseng Araliaceae Dried leaf China 100 mg/kgPancratium Amaryllidaceae Dried bulb Turkey 1,2 mg/kg

Introducion 36

Paullinia cupana Sapindaceae Dried seed Brazil 200 mg/kgPeganum harmala Zygophyllacea Dried entire Iraq 150 mg/kgPersea americana Lauraceae Dried seed Brazil 80 mg/kgPhotinia serrulata Rosaceae Dried Taiwan 25 mg/kgPhyla nodiflora Verbenaceae Dried leaf Africa 0,5 mg/kgPinus koraiensis Pinaceae Leaf essentialChina 0,217 ml/kgPiper abutiloides Piperaceae Fresh leaf Brazil 1 mg/kgPiper cincinnatoris Piperaceae Fresh leaf Brazil 1 mg/kgPiper lindbergii Piperaceae Fresh leaf Brazil 1 mg/kgPiper longum Piperaceae Unripe-dried China 125 mg/kgPiscidia erythrina Fabaceae Dried bark USA 600 mg/kgPlatycodon Campanulaceae Dried root Roumania 2 mg/kgPolygala cyparissias Polygalaceae Dried leaf- Brazil 3; 50 and 100 mg/kgPolypodium vulgare Polypodiaceae Dried root India 300 mg/kgPongamia pinnata Fabaceae Dried root India 50 mg/kgPortulaca Portulacaceae Dried aerial United 400 mg/kgPortulaca oleracea Portulacaceae Dried aerial United 400 mg/kgPrunus spinosa Rosaceae Dried Spain 750 mg/kgPsammosilene Caryophyllacea Dried root China 5 mg/kgPsidium pohlianum Myrtaceae Leaf essentialBrazil 40 and 100 mg/kgPsychotria Rubiaceae Dried leaf Brazil 350 mg/kgPsychotria colorata Rubiaceae Dried flowersBrazil 25 mg/kgPtychopetalum Olacaceae Dried leaf Brazil 200 mg/kgPycnocomon Dipsacaceae Dried aerial Spain 300 mg/kgQuercus infectoria Fabaceae Galls Iran not statedQuercus lineata Fabaceae Stembark India 50 mg/kgRandia siamensis Rubiaceae not specified Thailand 300 mg/kgRanunculus Ranunculaceae Dried entire China 1 and 2,5 mg/kgRhamnus Rhamnaceae Bark India 200 mg/kgRhazya stricta Apocynaceae Dried aerial Saudi 500 mg/kgRicinus communis Euphorbiaceae ootbark India 250 mg/kgRoylea elegans Lamiaceae Dried leaf India 350 and 500 mg/kgSalvia haematodes Lamiaceae Fresh root India 500 mg/kgSantolina Asteraceae Dried aerial Spain 60 and 300 mg/kgSaussurea Asteraceae Entire plant China 20 mg/kgSenna italica Fabaceae Dried leaf United 0,25 and 0,5 mg/kgSerjania communis Sapindaceae stembark Brazil 1 mg/kgSideritis Lamiaceae Dried aerial Spain not statedSiphocampylus Campanulaceae Dried leaf- Brazil 300 mg/kgStephania dinklagei Menispermacea Dried stem Nigeria 0,5 ml/kgStefania wightli Menispermacea Dried entire India 20 mg/kgStrychnos nux- Loganiaceae Dried seed China mcg/kgSynedrella nodiflora Asteraceae Dried entire Africa 0,5 mg/kgTabebuia Bignoniaceae Dried wood Brazil 200 mg/kgTabernaemontana Apocynaceae Dried stem Thailand 0,5 and 250 mg/kgTamarix milotica Tamaricaceae Pod Saudi 500 mg/kgTaraxacum officinaleAsteracea Dried leaf Italy 0,1 mg/kgTeclea nobilis Rutaceae Dried leaf Ethiopia 50 mg/kgTecomella undulata Bignoniaceae Dried entire Pakistan 300 mg/kgTeucrium Lamiaceae Dried leaf- Spain 200 mg/kgTheobroma Sterculiaceae Dried seed Brazil 80 mg/kgThymus vulgaris Lamiaceae Aerial parts S. Arabia 500 mg/kg

Introducion 37

Tinospora cordifolia Menispermacea Not specified India not statedTorresea cearensis Fabaceae stembark Brazil 200 and 400 mg/kgTrachelospermum Apocynaceae Dried stem Taiwan 26,8 mg/kgTrema guineensis Ulmaceae Dried leaf Tanzania 500 and 1000 mg/kgTrianthema Alzoaceae Dried entire India 100 mg/kgTribulus terrestris Zygophyllacea Dried aerial Iraq 150 mg/kgTrigonella anguina Fabaceae Dried entire

plant

Saudi

Arabia

500 mg/kg

Unidentified species Lamiaceae Dried leaf Jordan 400 mg/kgUrtica dioica Urticaceae Dried Spain 1200 mg/kgValeriana jatamansi Valerianaceae Dried leaf India 2 mgVernonia condensata Asteraceae Dried leaf Brazil 241 mg/kgViola mandshurica Violaceae Dried aerial Korea 5 mg/kgVitex negundo Verbenaceae Fruit India 3 mgZingiber officinale Zingiberaceae Dried Brazil 200 mg/kg

1.12 DIABETES62-65

Diabetes was known even in ancient times. The name of this disease, which is

characterised by excessive flow of urine and insatiable thirst, was coined by the

Graeco-Roman physician Aretaeus of Cappadocia (approx. 80–130 A.D.) and is

derived from the Greek word diabainein (‘to flow through’). The adjective mellitus,

which comes from Latin and means ‘honey-sweet’, was added by the German

physician Johann Peter Frank (1745–1821) in order to distinguish diabetes mellitus, or

‘sugar diabetes’, from diabetes insipidus. Johann Peter Frank was also who in 1790,

by introducing a yeast fermentation test for the quantitative determination of urinary

glucose, relieved the physicians of his time of the need to taste their patients’ urine.

In diabetes insipidus an excessive amount of urine is produced as a result of a

disturbance of the hormonal control of reabsorption of water in the kidneys. Untreated

diabetes mellitus, by contrast, is characterised by high blood glucose levels due either

to diminish or absent insulin production or to reduce effectiveness of insulin in the

body. Various types of diabetes mellitus are distinguished on the basis of their causes

and natural history. The classification of diabetes mellitus put forward in 1997 by the

American Diabetes Association.

In people with diabetes, blood sugar levels remain high. This may be because insulin

is not being produced at all, is not made at sufficient levels, or is not as effective as it

should be. The most common forms of diabetes are type 1 diabetes (5%), which is an

autoimmune disorder, and type 2 diabetes (95%), which is associated with obesity.

Introducion 38

Gestational diabetes is a form of diabetes that occurs in pregnancy, and other forms of

diabetes are very rare and are caused by a single gene mutation.

For many years, scientists have been searching for clues in our genetic makeup that

may explain why some people are more likely to get diabetes than others are. "The

Genetic Landscape of Diabetes" introduces some of the genes that have been

suggested to play a role in the development of diabetes.

Physicians have observed the effects of diabetes for thousands of years. For much of

this time, little was known about this fatal disease that caused wasting away of the

body, extreme thirst, and frequent urination. It wasn't until 1922 that the first patient

was successfully treated with insulin.

“Insulin is not a cure for diabetes; it is a treatment. It enables the diabetic to burn

sufficient carbohydrates, so that proteins and fats may be added to the diet in

sufficient quantities to provide energy for the economic burdens of life”.

Definition

The term diabetes mellitus describes a metabolic disorder of multiple aetiology

characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and

protein metabolism resulting from defects in insulin secretion, insulin action, or both.

The effects of diabetes mellitus include long-term damage, dysfunction and failure of

various organs. Diabetes mellitus may present with characteristic symptoms such as

thirst, polyuria, blurring of vision, and weight loss. In its most severe forms,

ketoacidosis or a non-ketotic hyperosmolar state may develop and lead to stupor,

coma and, in absence of effective treatment, death. Often symptoms are not severe, or

may be absent, and consequently hyperglycaemia sufficient to cause pathological and

functional changes may be present for a long time before the diagnosis is made. The

long-term effects of diabetes mellitus include progressive development of the specific

complications of retinopathy with potential blindness, nephropathy that may lead to

renal failure, and/or neuropathy with risk of foot ulcers, amputation, Charcot joints,

and features of autonomic dysfunction, including sexual dysfunction. People with

diabetes are at increased risk of cardiovascular, peripheral vascular and

cerebrovascular disease.

Several pathogenetic processes are involved in the development of diabetes. These

include processes which destroy the beta cells of the pancreas with consequent insulin

deficiency, and others that result in resistance to insulin action. The abnormalities of

Introducion 39

carbohydrate, fat and protein metabolism are due to deficient action of insulin on

target tissues resulting from insensitivity or lack of insulin.

Signs and symptoms

The classical symptoms of diabetes are polyuria (frequent urination),

polydipsia (increased thirst) and polyphagia (increased hunger). Symptoms may

develop rapidly (weeks or months) in type 1 diabetes while in type 2 diabetes they

usually develop much more slowly and may be subtle or absent.

Prolonged high blood glucose causes glucose absorption, which leads to changes in

the shape of the lenses of the eyes, resulting in vision changes; sustained sensible

glucose control usually returns the lens to its original shape. Blurred vision is a

common complaint leading to a diabetes diagnosis; type 1 should always be suspected

in cases of rapid vision change, whereas with type 2 changes is generally more

gradual, but should still be suspected.

People (usually with type 1 diabetes) may also present with diabetic ketoacidosis, a

state of metabolic dysregulation characterized by the smell of acetone; a rapid, deep

breathing known as kussmal breathing; nausea; vomiting and abdominal pain; and

altered states of consciousness.

A rarer but equally severe possibility is hyperosmolar nonketotic state, which is more

common in type 2 diabetes and is mainly the result of dehydration. Often, the patient

has been drinking extreme amounts of sugar-containing drinks, leading to a vicious

circle in regard to the water loss.

A number of skin rashes can occur in diabetes that are collectively known as diabetic

dermadromes.

Classification

Earlier classifications

The first widely accepted classification of diabetes mellitus was published by WHO in

1980 and, in modified form, in 1985 . The 1980 and 1985 classifications of diabetes

mellitus and allied categories of glucose intolerance included clinical classes and two

statistical risk classes. The 1980 Expert Committee proposed two major classes of

diabetes mellitus and named them, IDDM or Type 1, and NIDDM or Type 2. In the

1985 Study Group Report the terms Type 1 and Type 2 were omitted, but the classes

IDDM and NIDDM were retained, and a class of Malnutrition-related Diabetes

Introducion 40

Mellitus (MRDM) was introduced. In both the 1980 and 1985 reports other classes of

diabetes included Other Types and Impaired Glucose Tolerance (IGT) as well as

Gestational Diabetes Mellitus (GDM). These were reflected in the subsequent

International Nomenclature of Diseases (IND) in 1991, and the tenth revision of the

International Classification of Diseases (ICD-10) in 1992. The 1985 classification was

widely accepted and is used internationally. It represented a compromise between

clinical and aetiological classification and allowed classification of individual subjects

and patients in a clinically useful manner even when the specific cause or aetiology

was unknown. The recommended classification includes both staging of diabetes

mellitus based on clinical descriptive criteria and a complementary aetiological

classification.

Revised classification

The classification encompasses both clinical stages and aetiological types of diabetes

mellitus and other categories of hyperglycaemia, as suggested by Kuzuya and

Matsuda.

The clinical staging reflects that diabetes, regardless of its aetiology, progresses

through several clinical stages during its natural history. Moreover, individual subjects

may move from stage to stage in either direction. Persons who have, or who are

developing, diabetes mellitus can be categorized by stage according to the clinical

characteristics, even in the absence of information concerning the underlying

aetiology. The classification by aetiological type results from improved understanding

of the causes of diabetes mellitus.

Application of the new classification

The new classification contains stages which reflect the various degrees of

hyperglycaemia in individual subjects with any of the disease processes which may

lead to diabetes mellitus.

All subjects with diabetes mellitus can be categorized according to clinical stage, and

this is achievable in all circumstances. The stage of glycaemia may change over time

depending on the extent of the underlying disease processes. The disease process may

be present but may not have progressed far enough to cause hyperglycaemia. The

aetiological classification reflects the fact that the defect or process which may lead to

diabetes may be identifiable at any stage in the development of diabetes even at the

stage of normoglycaemia. Thus the presence of islet cell antibodies in a

Introducion 41

normoglycaemic individual makes it likely that that person has the Type 1

autoimmune process. Unfortunately there are few sensitive or highly specific

indicators of the Type 2 process at present, although these are likely to be revealed as

aetiology is more clearly defined. The same disease processes can cause impaired

fasting glycaemia and/or impaired glucose tolerance without fulfilling the criteria for

the diagnosis of diabetes mellitus. In some individuals with diabetes, adequate

glycaemic control can be achieved with weight reduction, exercise and/or oral agents.

These individuals, therefore, do not require insulin and may even revert to IGT or

normoglycaemia. Other individuals require insulin for adequate glycaemic control but

can survive without it. These individuals, by definition, have some residual insulin

secretion. Individuals with extensive beta-cell destruction, and therefore no residual

insulin secretion, require insulin for survival. The severity of the metabolic

abnormality can either regress (e.g. with weight reduction), progress (e.g. with weight

gain), or stay the same.

Major types of diabetes mellitus

Most cases of diabetes mellitus fall into three broad categories: type 1, type 2

and gestational diabetes. A few other types are described. The term diabetes, without

qualification, usually refers to diabetes mellitus. The rare disease diabetes

insipidus has similar symptoms as diabetes mellitus, but without disturbances in the

sugar metabolism (insipidus meaning "without taste" in Latin).

The term "type 1 diabetes" has replaced several former terms, including childhood-

onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus (IDDM).

Likewise, the term "type 2 diabetes" has replaced several former terms, including

adult-onset diabetes, obesity-related diabetes, and non-insulin-dependent diabetes

mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard

nomenclature. Various sources have defined "type 3 diabetes" as: gestational

diabetes insulin-resistant type 1 diabetes (or "double diabetes"), type 2 diabetes which

has progressed to require injected insulin, and latent autoimmune diabetes of adults.

Type 1 diabetes

Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of

the islets of Langerhans the pancreas leading to insulin deficiency. This type of

diabetes can be further classified as immune-mediated or idiopathic. The majority of

type 1 diabetes is of the immune-mediated nature, where beta cell loss is a T-cell

Introducion 42

mediated autoimmune attack. There is no known preventive measure against type 1

diabetes, which causes approximately 10% of diabetes mellitus cases in North

America and Europe. Most affected people are otherwise healthy and of a healthy

weight when onset occurs. Sensitivity and responsiveness to insulin are usually

normal, especially in the early stages. Type 1 diabetes can affect children or adults but

was traditionally termed "juvenile diabetes" because it represents a majority of the

diabetes cases in children.

Type 2 diabetes

Type 2 diabetes mellitus is characterized by insulin resistance which may be

combined with relatively reduced insulin secretion. The defective responsiveness of

body tissues to insulin is believed to involve the insulin receptor. However, the

specific defects are not known. Diabetes mellitus due to a known defect are classified

separately. Type 2 diabetes is the most common type.

In the early stage of type 2 diabetes, the predominant abnormality is reduced insulin

sensitivity. At this stage hyperglycaemia can be reversed by a variety of measures

and medications that improve insulin sensitivity or reduce glucose production by

the liver.

Gestational diabetes

Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects,

involving a combination of relatively inadequate insulin secretion and responsiveness.

It occurs in about 2%–5% of all pregnancies and may improve or disappear after

delivery. Gestational diabetes is fully treatable but requires careful medical

supervision throughout the pregnancy. About 20%–50% of affected women develop

type 2 diabetes later in life.

Even though it may be transient, untreated gestational diabetes can damage the health

of the fetus or mother. Risks to the baby include macrosomia (high birth weight),

congenital cardiac and central nervous system anomalies, and skeletal muscle

malformations. Increased fetal insulin may inhibit fetal surfactant production and

cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood

cell destruction. In severe cases, perinatal death may occur, most commonly as a

result of poor placental perfusion due to vascular impairment. Labor induction may be

indicated with decreased placental function. A caesarean section may be performed if

Introducion 43

there is marked fetal distress or an increased risk of injury associated

with macrosomia, such as shoulder dystocia.

A 2008 study completed in the U.S. found that the number of American women

entering pregnancy with preexisting diabetes is increasing. In fact the rate of diabetes

in expectant mothers has more than doubled in the past 6 years. This is particularly

problematic as diabetes raises the risk of complications during pregnancy, as well as

increasing the potential that the children of diabetic mothers will also become diabetic

in the future.

Other types

Pre-diabetes indicates a condition that occurs when a person's blood glucose levels are

higher than normal but not high enough for a diagnosis of type 2 diabetes. Many

people destined to develop type 2 diabetes spend many years in a state of pre-diabetes

which has been termed "America's largest healthcare epidemic."

Latent autoimmune diabetes of adults is a condition in which Type 1

diabetes develops in adults. Adults with LADA are frequently initially misdiagnosed

as having Type 2 diabetes, based on age rather than etiology.

Other Specific Types:

Genetic defects of beta-cell function• Chromosome 20, HNF4alpha (MODY1)• Chromosome 7, glucokinase (MODY2)• Chromosome 12, HNF1alpha (MODY3)• Chromosome 13, IPF-1 (MODY4)• Mitochondrial DNA 3243 mutation

Genetic defects in insulin action

• Type A insulin resistance• Leprechaunism• Rabson-Mendenhall syndrome• Lipoatrophic diabetes

Diseases of the exocrine pancreas

• Fibrocalculous pancreatopathy• Pancreatitis• Trauma / pancreatectomy• Neoplasia• Cystic fibrosis• Haemochromatosis

Endocrinopathies

• Cushing's syndrome

Introducion 44

• Acromegaly• Phaeochromocytoma• Glucagonoma• Hyperthyroidism• Somatostatinoma

Drug- or chemical-induced Infections

• Congenital rubella• Cytomegalovirus• Others

Uncommon forms of immune-mediated diabetes

• Insulin autoimmune syndrome (antibodies to insulin)• Anti-insulin receptor antibodies• "Stiff Man" syndrome

Other genetic syndromes

Genetic defects of beta-cell function

Several forms of the diabetic state may be associated with monogenic defects in beta-

cell function, frequently characterized by onset of mild hyperglycaemia at an early

age (generally before age 25 years). They are usually inherited in an autosomal

dominant pattern. Patients with these forms of diabetes, formerly referred to as

maturity-onset diabetes of the young (MODY), have impaired insulin secretion with

minimal or no defect in insulin action. Abnormalities at three genetic loci on different

chromosomes have now been characterized. The most common form is associated

with mutations on chromosome 12 in a hepatic nuclear transcription factor referred to

as HNF1alpha. A second form is associated with mutations in the glucokinase gene on

chromosome 7p. Glucokinase converts glucose to glucose-6-phosphate, the

metabolism of which in turn stimulates insulin secretion by the beta cell. Thus,

glucokinase serves as the "glucose sensor" for the beta cell. Because of defects in the

glucokinase gene, increased levels of glucose are necessary to elicit normal levels of

insulin secretion. A third form is associated with a mutation in the HNF4alpha gene

on chromosome 20q. HNF4alpha is a transcription factor which is involved in the

regulation of the expression of HNF1alpha. A fourth variant has recently been

ascribed to mutations in another transcription factor gene, IPF-1, which in its

homozygous form leads to total pancreatic agenesis. Specific genetic defects in other

individuals who have a similar clinical presentation are currently being defined.

Introducion 45

Point mutations in mitochondrial DNA have been found to be associated with diabetes

mellitus and deafness. The most common mutation occurs at position 3243 in the

tRNA leucine gene, leading to an A to G substitution. An identical lesion occurs in the

MELAS syndrome (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and

Stroke-like syndrome); however, diabetes is not part of this syndrome, suggesting for

unknown reasons different phenotypic expressions of this genetic lesion.

Genetic abnormalities that result in the inability to convert proinsulin to insulin have

been identified in a few families. Such traits are usually inherited in an autosomal

dominant pattern and the resultant carbohydrate intolerance is mild. Similarly, mutant

insulin molecules with impaired receptor binding have been identified in a few

families. These are also associated with autosomal inheritance and either normal or

only mildly impaired carbohydrate metabolism.

Genetic defects in insulin action

There are some unusual causes of diabetes which result from genetically determined

abnormalities of insulin action. The metabolic abnormalities associated with

mutations of the insulin receptor may range from hyperinsulinaemia and modest

hyperglycaemia to symptomatic diabetes. Some individuals with these mutations have

acanthosis nigricans. Women may have virilization and have enlarged, cystic ovaries.

In the past, this syndrome was termed Type A insulin resistance. Leprechaunism and

Rabson-Mendenhall syndrome are two paediatric syndromes that have mutations in

the insulin receptor gene with subsequent alterations in insulin receptor function and

extreme insulin resistance. The former has characteristic facial features while the

latter is associated with abnormalities of teeth and nails and pineal gland hyperplasia.

Diseases of the exocrine pancreas

Any process that diffusely injures the pancreas can cause diabetes. Acquired processes

include pancreatitis, trauma, infection, pancreatic carcinoma, and pancreatectomy.

With the exception of cancer, damage to the pancreas must be extensive for diabetes

to occur. However, adenocarcinomas that involve only a small portion of the pancreas

have been associated with diabetes. This implies a mechanism other than simple

reduction in beta-cell mass. If extensive enough, cystic fibrosis and

haemochromatosis will also damage beta cells and impair insulin secretion.

Fibrocalculous pancreatopathy may be accompanied by abdominal pain radiating to

Introducion 46

the back and pancreatic calcification on X-ray and ductal dilatation. Pancreatic

fibrosis and calcified stones in the exocrine ducts are found at autopsy.

Endocrinopathies

Several hormones (e.g. growth hormone, cortisol, glucagon, epinephrine) antagonize

insulin action. Diseases associated with excess secretion of these hormones can cause

diabetes (e.g. Acromegaly, Cushing's Syndrome, Glucagonoma and

Phaeochromocytoma). These forms of hyperglycaemia typically resolve when the

hormone excess is removed.

Somatostatinoma, and aldosteronoma-induced hypokalaemia, can cause diabetes, at

least in part by inhibiting insulin secretion. Hyperglycaemia generally resolves

following successful removal of the tumour.

Drug- or chemical-induced diabetes

Many drugs can impair insulin secretion. These drugs may not, by themselves, cause

diabetes but they may precipitate diabetes in persons with insulin resistance. In such

cases, the classification is ambiguous, as the primacy of beta-cell dysfunction or

insulin resistance is unknown. Certain toxins such as Vacor (a rat poison) and

pentamidine can permanently destroy pancreatic beta cells. Fortunately, such drug

reactions are rare. There are also many drugs and hormones which can impair insulin

action. Examples include nicotinic acid and glucocorticoids. The list shown in Table 4

is not all-inclusive, but reflects the more commonly recognized drug-, hormone-, or

toxin-induced forms of diabetes and hyperglycaemia.

Drug- or Chemical-induced Diabetes

• Nicotinic acid• Glucocorticoids• Thyroid hormone• Alpha-adrenergic agonists• Beta-adrenergic agonists• Thiazides• Dilantin• Pentamidine• Vacor• Interferon-alpha therapy

Uncommon but specific forms of immune-mediated diabetes mellitus

Diabetes may be associated with several immunological diseases with a pathogenesis

or aetiology different from that which leads to the Type 1 diabetes process.

Postprandial hyperglycaemia of a severity sufficient to fulfil the criteria for diabetes

Introducion 47

has been reported in rare individuals who spontaneously develop insulin

autoantibodies. However, these individuals generally present with symptoms of

hypoglycaemia rather than hyperglycaemia. The "stiff man syndrome" is an

autoimmune disorder of the central nervous system, characterized by stiffness of the

axial muscles with painful spasms. Affected people usually have high titres of the

GAD autoantibodies and approximately one-half will develop diabetes. Patients

receiving interferon alpha have been reported to develop diabetes associated with islet

cell autoantibodies and, in certain instances, severe insulin deficiency.

Anti-insulin receptor antibodies can cause diabetes by binding to the insulin receptor

thereby reducing the binding of insulin to target tissues. However, these antibodies

also can act as an insulin agonist after binding to the receptor and can thereby cause

hypoglycaemia. Anti-insulin receptor antibodies are occasionally found in patients

with systemic lupus erythematosus and other autoimmune diseases. As in other states

of extreme insulin resistance, patients with anti-insulin receptor antibodies often have

acanthosis nigricans. In the past, this syndrome was termed Type B insulin resistance.

Other genetic syndromes sometimes associated with diabetes

Many genetic syndromes are accompanied by an increased incidence of diabetes

mellitus. These include the chromosomal abnormalities of Down's syndrome,

Klinefelter's syndrome and Turner's syndrome. Wolfram's syndrome is an autosomal

recessive disorder characterized by insulin-deficient diabetes and the absence of beta

cells at autopsy. Additional manifestations include diabetes insipidus, hypogonadism,

optic atrophy, and neural deafness.

Other Genetic Syndromes Sometimes Associated with Diabetes

• Down's syndrome• Friedreich's ataxia• Huntington's chorea• Klinefelter's syndrome• Lawrence-Moon-Biedel syndrome• Myotonic dystrophy• Porphyria• Prader-Willi syndrome• Turner's syndrome• Wolfram's syndrome

Table 1.4: Medicinal Herbs used in the treatment of diabetes from India

Introducion 48

Botanical Name

(Family)

Local

Name

Part Use Habit Traditional therapy

Abelomoschus

esculentus well

(Malvaceae)

Dheros Fruit Herb Two vertically

dissected fresh fruit are

soaked overnight in ½

glass cold water and

that leech ate water is

taken every morning.Abrus precatorius

L. (Fabaceae)

Ratti

(Gumchi)

Leaves Climbing Juice twice a 25 day.

Aegle marmelos

Correa.

(Rutaceae)

Beal Leaves Tree One gram gum is eaten

along with betleafe

once daily.Allium cepa. (L.)

(Liliaceae)

Pyaz Bulb Herb Use of raw vegetable

along with rice.Allium sativum

(L.) (Liliaceae)

Lesun Bulb Herb A raw bulbet are eaten

once dailyArtocarpus

heterophyllus

Lamk (Moraceae)

Katahal Leaves Tree About ½ cup juice of

fresh tender leaves is

taken once dailyAndrographis

paniculata Nees

Nilavembu.

(Acanthaceae)

Kalmegh Leaves Herb Decoction drink 3 time

per day

Annona squamosa

L. Sita

(Annonaceae)

Sitaphal Leaves Tree Powder with water

daily in the morning

Aristolochia

bracteolata Retz.

Israrmuli

(Aristolochiaceae)

Kidmar Leaves Herb Powder with water

daily in the morning

Asparagus

racemosus Willd.

(Liliaceae)

Satawar Tubrous

root

Herb Powder mixed with leaf

powder Gymina

salvester twice per day

for 30 days

Introducion 49

Azadirachta indica

(A) Juss.

(Meliaceae)

Neem Flower Tree Roasted flower or bark

powder with bulfer

milk for 40 daysAcalypha Indica

(L.)

(Euphorbiaceae)

Kuppi Leaves Herb Leaf juice two tea

spoon full is given

daily a one month for

diabetesArgyreia nervosa

(Burm. F.) Boj

(Convolvulaceae)

Samdar

kapat

Leaves Herb Pills made from the leaf

past is given to diabetes

patients for a long

times.Alpinia galanga

(L.) SW.

(Zingiberaceae)

Kulangan Root Herb -

Aloe barbadensis

(L.) Burm. F.

(Liliaceae)

Gwarpatha Leaf Herb -

Atropa belladonna

(Solanaceae)

Cheelatubar Seed Tree -

Bauhinia

variegata L.

(Caesalpiniaceae)

Kachnar Root Tree -

Boerhaavia diffusa

L. (Nyctaginaceae)

Itsit Leaves Herb -

Benincasa hispida

(Cucurbitaceae)

Petha Seed Climber -

Bacopa monnieri

(L.) Penn.

(Scrophulariaceae

)

Nariabrahmi Leaves Herb Agueous leaf juice is

given twice a day for

one month for diabetes.

Butea

monosperma

(Lamk) Taub

(Fabaceae)

Dhak

(Palas)

Leaves Tree Aqueous extract of

leaves and fruit is given

2 tea spoon full once

day for diabetes for a

long times.Bougainvillea

spectabilis (Willd)

Bogainvilla Leaves Shrub Past made into pills

twice per day for 25

Introducion 50

(Nyctaginaceae) days

Berrya cordifolia

(Tiliaceae)

Burret Leaves Tree -

Chonemorpha

fragrans

(Apocynaceae)

Garphedaro Root Shrub -

Chlorophytum

borivilianum

Roxb. (Liliaceae)

Safed Musli Root Herb -

Caesalpinia

pulcherrima L.

Roxb.

(Caesalpiniaceae)

Mayilkonnal

(Gulutora)

Leaves Shrub -

Crocus sativus L.

(Iridaceae)

Kesar Flower Herb -

Cassia sophera L.

(Caesalpiniaceae)

Thaonum Bark Shrub Bark and powder seed

mixed with honey is

given in diabetesCassia fistula (L.)

(Caesalpiniaceae)

Amaltas Fruit Tree Fruit pulp is given for

diabetesCassia auriculata

L.

(Caesalpiniaceae)

Aauaria Leaves Shrub Juice for 20 days

Cassia tora L.

(Caesalpiniaceae)

Chakora Leaves Herb Leaf juice for 20 days

Cassia

occidentalis L.

(Caesalpiniaceae)

Pelaya Leaves Shrub Powder with milk twice

a day for 20

Catharanthus

roseus (L.) G Don

(Apocynaceae)

Sadabahar Leaves Herb Leaf juice is given for

diabetes

Centella asiatica

(L.) Urban.

(Apiaceae)

Brahmi Leaves Herb Leaf juice is given for

the treatment to

diabetes for a long timeCissampelos

pareira (L.)

Akanadi Root Climber The root powder with

water is taken once a

Introducion 51

(Menispermaceae) day for 40 days treating

diabetes.Clerodendrum

multiflorum

(Burmf) O.Ketze

(Verbanceae)

Arni Whol plant Shrub Aqueous extract of the

plant is given for

treatment of diabetes

Clitoria ternatea

(L.) (Fabaceae)

Aparajita Flower Twining The flower juice is

given for controlling

diabetes.Coccinia grandis

(L.) voigt.

(cucurbitaceae)

Kundru Leaves Shrub Aqueous extract of the

roots leaves and

mucilage from our fruit

used for diabetesCajanus cajan (L.)

millsp.

(Papilionaceae)

Arher Leaves Shrub About 2 tea spoon full

juice is given once

daily with few drop of

honey

Camellia sinensis

(L.) O Ktze.

(Theaceae)

Cha Leaves Tree Eatern raw

Cinnamomum

verum J.S. Presl

(Lauraceae)

Daruchini Bark Tree ½ tea spoon dust with

tea is given twice daily

in empty stomachCocos nucifera L.

(Arecaceae)

Coconut Fruit Tree Kernal and eaten daily

Cocolus hirsutus

(L.) diels

(Menipermaceae)

Jamtikibel Leaves Climber Leaf of juice given for

diabetes

Costus mercicanus

(kocnig)

(Zingiberaceae)

Costus Leaves Herb One leaves daily eaten

Cucumis sativus

Roxb.

(Cucurbitaceae)

Shasha Fruit Climber To reduce Sugar a

freshly collected green

fruit should beCuminum

cyminum m.L.

Jeera Seed Herb About 2mg. Seed

powder is taken with

Introducion 52

(Apiaceae) once dailyCarica papay L.

(Cariaceae)

Papeta Fruit Tree Juice is drunk 2 times

per daily.Cornus officinalis

Siebddet Zuee

(Cornaceae)

Cherry Peeudocarp Shrub -

Cressa cretical L.

(Conveolvulance)

Rudrar anti Whol plant Shrub -

Cyamopsis

tetragonoloba (L.)

(Leguminosceae)

Guargum Seed Shrub -

Hyptis suaveolens

is Well.

(Ranunculaceae)

Mameera Rhizome Herb -

Datura metel Linn.

(Solanaceae)

Dhatura

(Black)

Seed Shrub Crushed seed Ca25

mg/kg body Wight ore

given once dailyDaucas carota

Linn. Var. sativa

(Umbelliferaceae)

Gajara Root Herb Extract is used in

biosweets for reducing

blood suggerDiospyros

malabarica (Desr.)

Kostel.

(Ebenaceae)

Tendu Bark Tree About 5ml. extract if

taken orally daily acts

hypoglycamic

Dioscorea alata

(Dioscoreaceae)

Chuprialu Tubrous

root

Herb -

Dalbaergia sisso

Roxb. (Fabaceae)

Talhi

(Shishum)

Gum Tree Anti diabetes

Emblica officinalis

(Euphorbiaceae)

Amla Dry fruit Tree Powder on tea spoon

ful with milk twice per

dayEupatorium

purpureum L.

(Asteraceae)

Queen of

the meadow

root

Root Herb -

Ficus carica L.

(Moraceae)

Anjir Fruit Tree Fruit used as tonic 2

fruits used daily after

sowing early in the

Introducion 53

morning.Ficus

benghalensis L.

(Moraceae)

Bergad Bark Tree About 5mg bark is

sowked overnight in

water and the teechate

water is take orallyFicus religiosa L.

(Moraceae)

Pipal Bark Tree Bark extract is given

for diabetesFicus comosus L.

(Moraceae)

Gular Fruit Tree Flower used in jaundice

one flower eats daily

one week to cure

jaundice.Ficus glomer

Roxb. (Moraceae)

Atthi Young fruit Tree Juice twice a day for 20

daysFoeniculum

vulgare Mill

(Apiaceae)

Sonf Leaves Herb -

Fraxinus excelsior

(oleaceae)

Sum Seed Tree Anti diabetic

Gymnema

sylvestre (Retz.)

schult

(Asclepiadaceae)

Gudmar Leaves Climber -

Glycosmis

pentaphylla (Retz.)

DC. (Rutaceae)

Bannimb Leaves Shrub Leaf oil is given for

diabetes

Glycine max L.

(Merr.)

(Papilionaceae)

Soyabean Seed Herb Used of vegetable in

curry

Gossypium

herbaceum L.

(Malvaceae)

Kapas Seed Shrub About 2m. raw seed are

eaten twice daily

Galega officinalis

(Leguminosae)

Goat'srue Whol plant Herb -

Gardenia taitensis

D. (Rubiaceae)

Tiare Flower Tree -

Hemidesmus

indicus

Anantmul Root climber Aqueous extract of the

roots one table spoon

Introducion 54

(Asclepiadaceae) full is given for 9 day

for the treatment of

diabetes.Holarrhena

pubescens Wall.

Exg. Don

(Apocynaceae)

Kuchi Seed Tree About 2gm. Seed are

soaked in water

overnight and glass of

lecchate cold water is

taken in emply

stomach.Hydnoearpus

kurzii Warb.

(King)

(Flaciourtiaceae)

Chalmugura Seed Tree About 1gm seed

powder is taken orally

twice daily.

Holoptelea

Integrifolia

(Roxb.) planch.

(Ulmaceae)

Chilbil Leaves Tree -

Ipomoea

Mauritiana Jacq.

(Convolvulaceae)

Bhuikumra Root Climber About ½ cup fresh root

extract is taken once

dailyKyllinga

nemoralis

(Forester) Dandy

(Cyperaceae)

Gothubi Root Herb -

Madhuca indica

(Koenig)

Macbride

(Sapotaceae)

Mahua Inner bark Tree -

Muhiamatera

spatona

(Cucurbitaceae)

Agumaki Leaves Climber -

Mangifera indica

Linn.

(Anacardiaceae)

Aam Leaves Tree Oral administration of

aqueous extract of the

leaves gm/kg body

weight is commended.

Introducion 55

Manilkara zapota

(L.) P. Rosen

(Sapotaceae)

Safeda Root Tree The root are soaked

overnight and the

alcohol extract of the

some is given 20 gm/kg

body Wight.Moringa oleifera

Lam.

(Moringaceae)

Munga Fruit Tree The juice is

recommended the rice

daily for 7 days.Momordica

charantia L.

(Cucurbitaceae)

Karela Fruit Herb About bitter gourd if

eaten daily there will be

no chonce of diabetes.Musa paradisiaca

L. (Musaceae)

Kela Fruit Herb 23 tea spoon full juice

of plant is taken daily

along withMentha piperita L.

Emend. Huds.

(Lamiaceae)

Podina Fruit Herb -

Oxalis corniculata

L. (Oxalidaceae)

Khatkurla Wood Herb -

Ougeinia

oojeinensis

(Roxb.) Hochr.

(Fabaceae)

Sandan Seed Tree -

Oryza sativa Linn.

(Poaceae)

Dhan Root Herb -

Olea europaea

(Oleaceae)

Olive Oile Seed Tree Powder with milk twice

a day for 25 day.Phyllanthus

emblica L.

(Euphorbiaceae)

Amlaki Fruit Tree About 3-4 gm. Dry rind

powder is coten daily

along with a pinch of

rock solt.Psidium guajava

L. (Myrtaceae)

Amrud Fruit Tree Powder with buter milk

twice per day for days.Portulaca

oleracea

(Portulacaceae)

Golbhaji Leaves Herb About 10 mg. fresh

plant is boiled in cup of

water and the filtered

juice is taken twice

Introducion 56

dailyPunica granatum

L. (Punicoceae)

Anar Pericarp Tree One fruit daily eaten

Pterocorpus

Marsupium Roxb.

(Fabaceae)

Bijasal Bark Tree Aqueous extract of the

heard wood is given for

diabetes about 1 gm.

Past is taken.Pandanus

odoratisssimus

L.F. (Pandanaceae)

Kevda Root Tree -

Phascolus vulgaris

(Fabaceae)

French bean Seed Climber -

Picrorhiza kurroa

Pennell.

(Scrophulariaceae)

Kutki Rhizome Herb

-

Rhizphora

apiculate

(Rhizophoraceae)

Garjan Leaves Herb The extract of leaves

4mg/kg body Wight

given once daily

aqueous extract of the

heard wood is given for

diabetes about 1 gm.

Paste is taken.Ruta graveolens

(Rutaceae)

Aru Leaves Herb Powder 1 to 2 tea

spoon full once in a

week for 4 weeks.Rosa rugosa

thunb. (Rosaceae)

Japanese

rose

Flower Shrub -

Rubia cordifolia L.

(Rubiaceae)

Majith Root Herb -

Santalum album L.

(Santalaceae)

Swet

chandan

Stem Tree About 1 gm. Paste is

takenShorea rubusta

Gaertn. F.

(Dipterocarpaceae)

Sal Leaves Tree About 2 leaves are

crushed in ½ cup water

the juice is taken once

dailyStevia rubbendian

L. (Astraceae)

Sweet plant Leaf Herb -

Introducion 57

Syzgium jambos

L. (Myrtaceae)

Jamun Seed Tree One tea spoon full of

seed powder is given

twice daily

Strychonos

potatorum. L. F.

(Loganiaceae)

Nirmah Seed Tree -

Tectona grandis

L.F. (Verbenaceae)

Sagvan Seed Tree -

Terminalia arjuna

(Roxb. ex. DC.)

Arjun Stem bark Tree Extract is used in

biosweets for reducing

blood sluggerTerminala catappa

L. (Combretaceae)

Deshir

badam

Fruit Tree About 50 gm. Fruit is

sufficient for daily dose

about 2 in chess.Tragia involucrata

L. (Euphorbiaceae)

Barhan Root Herb -

Tragopgon

pratensis

(Astearaceae)

Goat's beard Root Herb

-

Trigonella

corniculata (L.)

(Papilioaceae)

Methi Seed Herb Soaked the 5 gm. Seed

over night drunk ½ cup

leech ate water once

daily.Vaccinium

myrthillus L.

Bilber Fruit Shrub -

Withania

somnifera (L.)

Dunal

(Solanaceae)

Aswagandh Root Shrub About 3 gm. Root

disconcotion is give

once daily long with

m.l. leaves extract of

thamkumi.Zanthoxytum or

matium DC.

(Rutaceae)

Tejphal Fruit Shrub -

Zingiber zerumbet

Rose. ex. Sm.

(Zingiberaceae)

Narkachur Rhizome Herb -

Introducion 58

1.13 HYPERLIPIDEMIA66-68

Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia (British English) involves

abnormally elevated levels of any or all lipids and/or lipoproteins in the blood. It is

the most common form of dyslipidemia (which also includes any decreased lipid

levels).

Lipids (fat-soluble molecules) are transported in a protein capsule. The size of that

capsule, or lipoprotein, determines its density. The lipoprotein density and type of

apolipoproteins it contains determines the fate of the particle and its influence on

metabolism.

Hyperlipidemias are divided in primary and secondary subtypes. Primary

hyperlipidemia is usually due to genetic causes (such as a mutation in a receptor

protein), while secondary hyperlipidemia arises due to other underlying causes such

as diabetes. Lipid and lipoprotein abnormalities are common in the general

population, and are regarded as a modifiable risk factor for cardiovascular disease due

to their influence on atherosclerosis. In addition, some forms may predispose to acute

pancreatitis.

Classification

Hyperlipidemias may basically be classified as either familial (also called primary)

caused by specific genetic abnormalities, or acquired (also called secondary) when

resulting from another underlying disorder that leads to alterations in plasma lipid and

lipoprotein metabolism. Also, hyperlipidemia may be idiopathic, that is, without

known cause.

Hyperlipidemias are also classified according to which types of lipids are elevated,

that is hypercholesterolemia, hypertriglyceridemia or both in combined

hyperlipidemia. Elevated levels of Lipoprotein(a) may also be classified as a form of

hyperlipidemia.

Familial (primary)

Familial hyperlipidemias are classified according to the Fredrickson classification

which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation.

It was later adopted by the World Health Organization (WHO). It does not directly

account for HDL, and it does not distinguish among the different genes that may be

Introducion 59

partially responsible for some of these conditions. It remains a popular system of

classification, but is considered dated by many.

Hyperlipoproteinemia type I

Type I hyperlipoproteinemia exists in several forms:

Lipoprotein lipase deficiency (Type Ia), due to a deficiency of lipoprotein lipase

(LPL) or altered apolipoprotein C2, resulting in elevated chylomicrons, the particles

that transfer fatty acids from the digestive tract to the liver.

Familial apoprotein CII deficiency (Type Ib), a condition caused by a lack of

lipoprotein lipase activator.

Chylomicronemia due to circulating inhibitor of lipoprotein lipase (Type Ic)

Type I hyperlipoproteinemia usually presents in childhood with eruptive xanthomata

and abdominal colic. Complications include retinal vein occlusion, acute pancreatitis,

steatosis and organomegaly, and lipaemia retinalis.

Hyperlipoproteinemia type II

Hyperlipoproteinemia type II, by far the most common form, is further classified into

type IIa and type IIb, depending mainly on whether there is elevation in the

triglyceride level in addition to LDL cholesterol.

Type IIa

Main article: Familial hypercholesterolemia

This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of

a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the

population) or the ApoB gene (0.2%). The familial form is characterized by tendon

xanthoma, xanthelasma and premature cardiovascular disease. The incidence of this

disease is about 1 in 500 for heterozygotes, and 1 in 1,000,000 for homozygotes.

Type IIb

The high VLDL levels are due to overproduction of substrates, including

triglycerides, acetyl CoA, and an increase in B-100 synthesis. They may also be

caused by the decreased clearance of LDL. Prevalence in the population is 10%.

Familial combined hyperlipoproteinemia (FCH)

Lysosomal acid lipase deficiency, often called (Cholesteryl ester storage disease)

Secondary combined hyperlipoproteinemia (usually in the context of metabolic

syndrome, for which it is a diagnostic criterion)

Introducion 60

Hyperlipoproteinemia type III

This form is due to high chylomicrons and IDL (intermediate density lipoprotein).

Also known as broad beta disease or dysbetalipoproteinemia, the most common cause

for this form is the presence of ApoE E2/E2 genotype. It is due to cholesterol-rich

VLDL (β-VLDL). Its prevalence has been estimated to be approximately 1 in 10,000.

Hyperlipoproteinemia type IV

Familial hypertriglyceridemia is an autosomal dominant condition occurring in

approximately 1% of the population.[6]

Hyperlipoproteinemia type V

Hyperlipoproteinemia type V is very similar to type I, but with high VLDL in addition

to chylomicrons.

It is also associated with glucose intolerance and hyperuricemia

Unclassified familial forms

Non-classified forms are extremely rare:

• Hyperalphalipoproteinemia

• Polygenic hypercholesterolemia

Acquired (secondary)

Acquired hyperlipidemias (also called secondary dyslipoproteinemias) often mimic

primary forms of hyperlipidemia and can have similar consequences. They may result

in increased risk of premature atherosclerosis or, when associated with marked

hypertriglyceridemia, may lead to pancreatitis and other complications of the

chylomicronemia syndrome. The most common causes of acquired hyperlipidemia

are:

• diabetes mellitus

• Use of drugs such as diuretics, beta blockers, and estrogens

• Other conditions leading to acquired hyperlipidemia include:

• Hypothyroidism

• renal failure

• nephrotic syndrome

• alcohol

• Some rare endocrine disorders and metabolic disorders

Treatment

Introducion 61

Treatment of the underlying condition, when possible, or discontinuation of the

offending drugs usually leads to an improvement in the hyperlipidemia. Specific lipid-

lowering therapy may be required in certain circumstances.

Another acquired cause of hyperlipidemia, although not always included in this

category, is postprandial hyperlipidemia, a normal increase following ingestion of

food.

Table 1.5: Fredrickson classification of Hyperlipidemias

Hyperli

po-

proteine

mia

OM

IMSynonyms Defect

Increase

d

lipoprot

ein

Main

symptoms

Treatm

ent

Serum

appear

ance

Estimat

ed

prevalen

ce

Type

I

a2386

00

Buerger-

Gruetz

syndrome, or

Familial

hyperchylomic

ronemia

Decrea

sed

lipopro

tein

lipase

(LPL) Chylomi

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Introducion 62

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Introduction 63

1.14 PLANT PROFILE

1.14.1 Abutilon muticum69-106

Abutilon is a large genus of approximately 150 species of broadleaf evergreens in the

mallow family, Malvaceae. The genus includes annuals, perennials, shrubs, and small

trees from 1–10 m tall, and is found in the tropical and subtropical regions of all

continents. The leaves are alternate, unlobed or palmately lobed with 3-7 lobes. The

flowers are conspicuous, with five petals, mostly red, pink, orange, yellow or white.

Common names include Abutilon, Chinese Bell Flower, Chinese Lantern, Mallow,

Indian Mallow, and Flowering Maple (for the maple-like leaves of some species,

although the genus is not related to the true maples). Abutilon species are used as food

plants by the larvae of some lepidoptera species including Yellow-banded Skipper

(which feeds exclusively on A. avicennae) and Chionodes mariona.

Common name: Abutilon, Indian Mallow

Fig. 1.1: Plant of Abutilon muticum

Scientific classification

Introduction 64

Kingdom PlantaePhylum AngiospermsClass Eudicot

Sub-Class RosidsOrder MalvalesFamily MalvaceaeGenus AbutilonSpecies muticum

Description

Perennial herb or shrub, 0.5-2 m tall, stellate pubescent. Leaves 2-16 cm across, ovate

to orbicular-ovate or orbicular, irregularly and minutely to coarsely serrate or

subentire or crenate, usually cordate at base, obtuse to acute or shortly acuminate at

apex, 7-9 nerved, stellate pubescent on both sides, scabrous above, more densely hairy

and velvety beneath, sometimes 3-angular near the apex; petiole 2-12 (-18) cm long,

stellate pubescent, velvety; stipules 6-8 mm long, 1 mm broad, linear, reflexed.

Flowers axillary, solitary or fascicled; pedicel 0.5-1.5 cm long, in fruit up to 3.5 cm,

articulate in the middle to near the apex. Calyx 7-8 mm long, in fruit up to 10 mm,

fused to the middle, pubescent on both sides; lobes ovate to deltoid, acuminate, 4-5

mm broad. Corolla 2-2.6 cm across, yellow to orange-yellow, 2-2.5 times the length

of calyx; petals 10-12 mm across, obovate, claw hairy on the margin. Staminal tube 4-

5 mm long, stellate pubescent. Fruit usually globose, sometimes truncate, 9-12 mm in

diameter; mericarps 27-39, usually obtuse, 6-7 mm long, 5-6 mm broad, separating

after dehiscence. Seeds usually 2 in each mericarp, rarely only 1 by abortion, 2 mm

across, pubescent, reniform.

Distribution

Tropical Africa, Arabia, India and Pakistan. It occurs in plains throughout Pakistan,

more common in Sindh.

Habitat

Present in sub-himalayan tract and hills upto 1,200 m and in hotter parts of India.

Cultivation

Abutilons are popular garden plants in subtropical areas. The hardiest species, A.

ochsenii and A. vitifolium from Chile, are hardy in warm temperate areas with

moderate frost down to about −10 °C (14.0 °F)

Introduction 65

Abutilon × hybridum is a popular group of hybrids that are semi-tropical, frost-tender

shrubs typically growing 2–3 m tall. The lantern-like buds open to solitary, pendulous,

bell- to cup-shaped flowers to 8 cm diameter with five overlapping petals and

significant staminal columns typical of the mallow family. Flowers come in red, pink,

yellow, white and pastel shades. Lobed, maple-like, light green leaves are often

variegated with white and yellow.

Velvetleaf has been grown in China since around 2000 BCE for its strong, jute-like

fibre. The seeds are eaten in China and Kashmir. The leaves are also edible. The

flowers and plants have a fruity scent. Velvetleaf grows primarily in cropland,

especially corn fields, and it can also be found on roadsides and in gardens. Velvetleaf

prefers rich and cultivated soils, such as those used in agriculture.

After being introduced to North America in the 1700s, velvetleaf has become an

invasive species in agricultural regions of the eastern and midwestern United States. It

is one of the most detrimental weeds to corn causing decreases of up to 34% of crop

yield if not controlled and costing hundreds of millions of dollars per year in control

and damage. Velvetleaf is an extremely competitive plant, so much so that it can steal

nutrients and water away from crops. Velvetleaf is controllable by herbicides.

Uses

It is sweet, cooling, digestive, laxative, expectorant, diuretic, astringent, analgesic,

anti-inflammatory, anthelmintic, demulcent and aphrodisiac. It is useful in gout,

tuberculosis, ulcers, bleeding disorders, and worms. Decoction used in toothache and

tender gums. Demulcents of leaves are locally applied to boils and ulcers. Roots are

prescribed in fever, chest affection and urethrities.

1.14.2 Celosia argentea107-153

Celosia is a small genus of edible and ornamental plants, similar in appearance and

uses to the amaranths. They are sometimes called cockscombs or wool flowers for

their brightly colored, woolly flower heads which resemble cockscombs. The name

"cockscomb" may be restricted to those whose flower heads are crested by fasciation.

Celosia argentea is a tender annual that is often grown in gardens. It is propagated by

seeds. The seeds are extremely small, up to 43,000 seeds per ounce.

The Century cultivars are usually taller (1-2 feet), and are bright red, yellow, orange,

or pink. The Kimono cultivars are generally smaller (4 inches - 1 foot), and have more

Introduction 66

muted colors, though similar to the Century cultivars. Other colors, such as white,

burgundy, orange-red, etc., can be found. Certain varieties will grow to 3-4 feet in

height.

Common names

Quail Grass or White Cock's Comb (Safed Murg), Cockscomb, Feathered amaranth,

Woolflower, Red fox, Prince, Anne Greens

Fig. 1.2: Plant of Celosia argentea

Scientific classification

Kingdom PlantaePhylum AngiospermsClass Magnoliopsida

Order CaryophyllalesFamily AmaranthaceaeGenus CelosiaSpecies argentea

Introduction 67

Description

Celosia argentea Plumosa' is a crop we produce in the summer and fall when it is

nearly impossible (because of the heat) to produce good quality stocks. The vibrantly

coloured spikes of these Celosia's draw attention to themselves. Besides the plumes

there are also Celosia's shapes like a "brain". These are called the Celosia argentea

Cristata.

The range of colours is red, orange, yellow and pink. Various shades in each colour

are available. Some production starts in July, with major production in August,

September and October. The "Fall colours" are really appreciated by all consumers.

Celosia is usually shipped in bunches of 5 stems. Normally there is no sleeve around

the bunch but a sleeve can be requested when bunches are intended for cash and carry

sales.

The celosias or cockscombs are erect, branching plants with oval or lance-shaped,

strongly veined leaves 2-6 in (5.1-15.2 cm) long and hundreds of tiny flowers packed

in dense, brightly colored flowerheads which usually stand above the foliage. The

wild form, Celosia argentea var. argentea is a weedy annual or short-lived perennial to

6 ft (1.8 m) tall, with erect plumes of silvery white flowers. C. argentea var. cristata

(a.k.a. C. cristata) is a tetraploid cultigen of garden origin with many cultivars

classified into several groups. These cultivars come with flowerheads in a variety of

shapes (some rather weird), and brilliant hot colors including red, orange, yellow,

purple and creamy white.

The Plumosa Group of cultivars (sometimes sold as Celosia 'Plumosa' or feathered

amaranth) have feathery plumelike flowerheads, 4-10 in (10.2-25.4 cm) tall, that look

a little like tiny Christmas trees. 'Apricot Brandy' is freely branched, to 20 in (50.8

cm) tall, with orange flowerheads. 'Forest Fire' has maroon leaves and bright scarlet

flowerheads. 'New Look' has purplish leaves and crimson flowerheads. 'Kimono

Series' cultivars are small, to 8 in (20.3 cm) tall, with flowerheads in rose, pink,

creamy white and red.

Cultivars in the Cristata Group have compact rounded, crested or fan-shaped

flowerheads with bizarre convoluted ridges. The flowerheads are 3-12 in (7.6-30.5

cm) across and look a little like velvety brains, cauliflower heads or roosters' combs.

'Big Chief Mix' is tall, to 3 ft (0.9 m), with cauliflower-shaped flowerheads to 6 in

Introduction 68

(15.2 cm) in diameter. 'Jewel Box Mix' is very small, to 8 in (20.3 cm), with bronzy

leaves and flowerheads in hot, bright colors including yellow, pink, salmon, gold and

red; the flowerheads are fan-shaped, like a rooster's comb.

The Spicata Group (often classified as a distinct species, C. spicata) includes cultivars

with slender, cylindrical pink or rose flowerheads which have a metallic sheen

because the individual flowers are silvery-white at their bases. 'Flaming Series'

cultivars are typical of this group.

Cultivation

These plants are of tropical origin, they grow best in full sunlight. The flowerheads

can last up to 8 weeks, and further growth can be promoted by removing dead

flowers.

Celosia plumosa, also known as "Prince of Wales Feathers," is a synonym for Celosia

argentea. "Flamingo Feathers" is a specific annual that can grow up to 2 feet in height.

The colors are predominantly pink to light violet, and the leaves are a darker green,

when compared to C. argentea.

Celosia requires rich, well-drained soil, with humus and manure added, and should be

kept constantly moist. It needs sun, and shelter from the wind, and grows to a height

of 1.5 to 2 feet.

Flowers

Its crested inflorescence is ornately rippled and brilliantly colored.

Propagation

Celosia is propagated from seed, and should be raised under glass in cooler climates.

Location

Celosia argentea occurs widely as a weed in the equatorial tropics of Africa, Asia and

South America. It may have originated in Asia and then spread to Africa and South

America with the help of people.

Moisture: The celosias require constant moisture, but a well drained soil. Water

before the soil dries out. Plants that survive periods of drought may become stunted

and flower only poorly if at all.

Hardiness: Celosias are warm weather annuals. They can be stunted if exposed to

temperatures below about 60ºF (15.5ºC). Celosias thrive in hot, humid weather.

Propagation: Many gardeners purchase their celosias in the bedding plant section at

Introduction 69

their local garden center. The best plants to get are those that haven't flowered yet.

Celosias are easy to start from seed. Sow shallowly in soil or potting mix at 70-75ºF

(21-24ºC), and set out when nighttime temperatures stay above 45º or 50ºF (7-10ºC).

Six week old seedlings should bloom in about two months.

Uses

Use celosias, especially the Plumosa types, in masses in the annual flower bed, or for

edging in front of taller flowers and perennials. (Some of the flower colors may be

just too dramatic to go well with other flowers.) The Cristata cultivars are good in

containers, and prized for Japanese flower arrangements. The flowerheads of the

Plumosa and Spicata cultivars are beautiful in fresh flower arrangements. The dried

flowerheads of all groups are excellent in dried arrangements where they retain their

color and don't disintegrate all over the place. Cut off flowerheads before the seeds

develop, strip off all the leaves, and dry as quickly as possible by hanging upside

down is a warm, well ventilated area. The leaves and flowers are edible and are grown

for such use in Africa and Southeast Asia.

As a food

A traditional food plant in Africa, this little-known vegetable has potential to improve

nutrition, boost food security, foster rural development and support sustainable

landcare. Celosia argentea var. argentea or Lagos spinach (a.k.a. quail grass, Soko,

Celosia, feather cockscomb) is a broadleaf annual leaf vegetable belonging to the

Amaranth family (Amaranthaceae). It grows widespread across northern South

America, tropical Africa, the West Indies, South, East and Southeast Asia where it is

grows as a native or naturalized wildflower, and is cultivated as a nutritious leafy

green vegetable. It is traditional fare in countries of Central and West Africa, and is

one of the leading leafy green vegetables in Nigeria, where it is known as ‘soko

yokoto’, meaning ‘make husbands fat and happy. Fresh Swiss chard Fresh water

spinach Creamed spinach Steamed kale Leaf vegetables, also called potherbs, greens,

or leafy greens, are plant leaves eaten as a vegetable, sometimes accompanied by

tender petioles and shoots.

As a garden plant

Seed production in these species can be very high, 200-700 kg per hectare. One ounce

of seed may contain up to 43,000 seeds. One thousand seeds can weigh 1.0-1.5 grams.

Depending upon the location and fertility of the soil, blossoms can last 8-10 weeks.

Introduction 70

1.14.3 Crotalaria burhia154-165

A low undershrub, c. 30-60 cm tall; branches numerous, hoary with dense appressed

pubescence. Leaves few, deciduous, simple, c. 0.6-2.5 cm long, c. 3-10 mm broad,

oblong, obtuse, pubescent on both sides. Inflorescence a 6-12-flowered, elongated

raceme. Pedicels very short; bracteoles 2. Calyx c. 8-9 mm long, pubescent, teeth

lanceolate. Corolla yellow, slightly exserted. Style slightly bearded at the top. Fruit c.

8-9 mm long, c. 4 mm or less wide, hairy, 3-4-seeded.

Common names

Benth, Saniya

Scientific classification

Kingdom Plantae

Phylum Angiosperms

Class Magnoliopsida

Order Fabales

Family Fabaceae

Genus Crotalaria

Species Burhia

Fig. 1.3: Plant of Crotalaria burhia

Introduction 71

Description

Crotalaria is a genus of herbaceous plants and woody shrubs in the Family Fabaceae

(Subfamily Faboideae) commonly known as rattlepods. Some 600 or more species of

Crotalaria are described world-wide, mostly from the tropics; at least 500 species are

known from Africa. Some species of Crotalaria are grown as ornamentals. The

common name rattlepod or rattlebox is derived from the fact that the seeds become

loose in the pod as they mature, and rattle when the pod is shaken. The name derives

from the Greek, κροταλον, meaning "castanet", and is the same root as the name for

the rattlesnakes (Crotalus).

Crotalaria species are used as food plants by the larvae of some Lepidoptera species

including Endoclita sericeus, Etiella Zinckenella and Utetheisa ornatrix. The toxic

alakaloids produced by some members of this genus are known to be incorporated by

Utetheisia larvae and used to secure their defense from predators. (Eisner et al., 2003)

Crotalaria spectabilis Roth was introduced to the US from India for green manure. As

a legume that supports nitrogen fixing bacteria, it is considered a "soil builder."

However, it is also poisonous to cattle (as are many legumes), and has spread rapidly

Introduction 72

throughout the Southeastern United States where it is now considered an invasive

species.

Alkaloid monocrotaline, the main toxic principle of Crotalaria spectabilis, is used to

induce experimental pulmonary hypertension in laboratory animals.

Crotalaria longirostrata, also known as "longbeak rattlebox" or as "chipilín", is a

common leafy vegetable in Oaxaca and Central America. It is considered a weed in

the United States

Distribution

Pakistan (Punjab, Sind, Baluchistan); India; Afghanistan. The origin is uncertain, but

is believed to be native to India and Pakistan. Now cultivated throughout India (from

the foothills of the Himalayas to Ceylon), Pakistan, in Uganda and Rhodesia, and in

the western Hemisphere (e.g. Brazil) where it was introduced early in the 19th

century.

Ecology

Sunnhemp is the fastest growing species of the genus and is very effective in

smothering weeds. Almost any well-drained soil is suitable for the kharif crop.

Sunnhemp grown during the rainy season is utilized mainly as a green manure, the

fiber not considered of good quality. For fiber sunnhemp is grown on fairly light well-

drained soils that retain sufficient moisture during the growing season. Sunnhemp is a

short-day crop, but vegetative growth is favored by long days, although seed set may

be poor. Although tolerant of drought, sunnhemp has low tolerance to salt and frost.

Ranging from Cool Temperate Steppe to Tropical Very Dry through Tropical Wet

Forest Life Zones, sunnhemp is reported to tolerate annual precipitation of 4.9 to 42.9

dm (mean of 29 cases = 14.9 dm), annual mean temperature of 8.4 to 27.5°C (mean of

29 cases = 22.5°C), and pH of 5.0 to 8.4 (mean of 24 cases = 6.2).

Cultivation

After plowing, seed is broadcast by hand or a device consisting of a canvas bag

containing the seed with a blower attached. Then the land is cross-plowed. Seed is

sown at different rates at different times depending on the use of the crop. In India

seed is broadcast for fiber at a rate of 96 kg/ha under dry growing conditions, and less

on irrigated fields. In Pakistan seed is sown at rate of 120 to 240 kg/ha. The heavy

seed rate insures upright erect stems which help to smother weeds, produces a finer

fiber and increases the yield. Height of stalks in crops varied from 1.15 m to 1.75 m

Introduction 73

(to 2 m), with an average thickness of 1.2 cm about the middle of the stalk. Seed is

sown in Africa in late Nov. and Dec., even as late as Jan., except for weeding, which

is usually not necessary if the land has been well prepared; no cultivation is required.

Sunnhemp is a dryland crop. Where irrigated, furrows are opened in fields separating

them into small plots. If there is no rain after sowing, field is irrigated along these

furrows. Crop is irrigated once in 10-15 days, lightly compared to other crops, like

tobacco and chilies. Too much moisture is harmful during the first 2 weeks after

germination. Seeds germinate rapidly. In about 3 days seedlings appear above ground

and soon form a thick cover. No manure is applied. Sunnhemp is often grown as a

green manure, in rotation with tobacco, vegetables, dry grains, rice, corn, cotton, also

sugar cane, pineapples, coffee, and orchard crops.

Uses

It is good soil binder and has got medicinal value.

1.14.4 Salvadora persica166-240

Salvadora persica (Arak, Galenia asiatica, Peelu, Pīlu, Salvadora indica, or

toothbrush tree), is a species of Salvadora

Common name

Salt Bush, Toothbrush, Pilu

Scientific classification

Kingdom Plantae

Phylum Angiosperms

Class MagnoliopsidaOrder Brassicales

Family Salvadoraceae

Genus SalvadoraSpecies persica

Fig. 1.4: Plant of Salvadora persica

Introduction 74

Description

Salvadora persica is a small tree or shrub with a crooked trunk, seldom more than one

foot in diameter. Its bark is scabrous and cracked, whitish with pendulous extremities.

The root bark of the tree is similar to sand, and the inner surfaces are an even lighter

shade of brown. It has a pleasant fragrance, as well as a warm and pungent taste.

Botanical Description

Salvadora persica is an evergreen shrub or small tree to 6-7 m; main trunk erect or

trailing with profusely branched, wide crown of crooked, straggling and drooping

branches; young branches green in colour; bark slightly rough, greyish-brown on

main stem, paler elsewhere. Leaves oblong-elliptic to almost circular, 3 x 7 cm, light

to dark green, rather fleshy, sometimes with wartlike glandular dots and dense, rather

loose hairs; apex broadly tapering to rounded, sharp-tipped; base broadly tapering;

margin entire; petiole up to 10 mm long; leaves in opposite pairs. Flowers greenish to

yellowish, very small, in loose, slender-branched axillary or terminal panicles, up to

10 cm long. Fruit spherical, fleshy, 5-10 mm in diameter, pink to scarlet when mature,

single seeded; seeds turn from pink to purple-red and are semi-transparent when

Introduction 75

mature. The generic name was given in 1749 in honour of an apothecary of

Barcelona, Juan Salvador y Bosca (1598-1681), by Dr Laurent Garcin, botanist,

traveller and plant collector. The true specimen of this species came, as the specific

name indicates, from Persia.

History

Salvadora persica is a popular chewing stick throughout the Indian subcontinent, as

well as the wider Muslim world.[9]Also commonly referred to as Miswak, many

Muslims consider chewing Salvadora persica to be a practice recommended by the

Prophet Muhammad. As of 2009, Botanic Gardens Conservation International has a

total of 8 Salvadora persica in conservation.

Scientific analysis

According to chemical and phytochemical analysis of Salvadora persica, there was an

occurrence of carbohydrates and/or trimethylamine; an alkaloid which may effectively

be salvadorine; chlorides; sulphur; terpenes; vitamin C; glycosides; large amounts of

fluoride and silica; small amounts of tannins, saponins, flavonoids and sterols.

Ecology

Natural Habitat

S. persica is widespread, notably in thorn shrubs, desert floodplains, river and stream

bank vegetation, and grassy savannahs. Prefers areas where groundwater is readily

available, by riverbanks, on perimeters of waterholes, in seasonally wet sites, and

along drainage lines in arid zones.

Also found in valleys, on dunes and on termite mounds. The tree is able to tolerate a

very dry environment with mean annual rainfall of less than 200 mm. highly salt

tolerant, it can grow on coastal regions and inland saline soils.

Geographic distribution

Native : Algeria, Angola, Cameroon, Chad, Egypt, Eritrea, Ethiopia, India, Iran,

Israel, Jordan, Kenya, Libyan Arab Jamahiriya, Malawi, Mali, Mauritania,

Mozambique, Niger, Nigeria, Oman, Pakistan, Saudi Arabia, Senegal, Somalia, South

Africa, Sri Lanka, Sudan, Syrian Arab Republic, Tanzania, Uganda, Yemen, Republic

of, Zambia, Zimbabwe.

Habitat

On saline lands and black cotton soil of peninsular India and Sri lanka.

Propagation methods

Introduction 76

Readily germinates from seed. Seeds exhibit no dormancy but the fruit pulp contains

germination inhibitors that should be removed before sowing. The process of seed

germination starts with imbibition in water at 30-35 deg. C for 24-72 hours, but under

saline conditions the absorption of water is dependent upon osmotic pressure of the

media and cell sap. Soaked, depulped seeds of S. persica will germinate in 24 hours.

Seeds have been raised in the nursery for up to 3 years prior to transplanting in the

field.

Tree Management

For high seed settings and seed oil content, harvesting is recommended 3 months after

seed setting. This may be due to the utilization of food reserve in the cotyledons for

the development of fruit pulp, and can be seen as the pulp content of fruit increases.

Coppicing is advantageous for the tree’s use as a fuel, and the branches are repeatedly

cut to produce short stems that are harvested for toothbrushes. S. persica is grown in

plantations or hedges. Salvadoras persica is generally a slow-growing tree.

Germplasm Management

Seed storage is orthodox; seeds can be stored with low moisture content. There are

about 3400 seeds/kg.

Uses

Root bark is tonic, stimulant and emmenagogue and used to relieve splenalgia. The

stem bark is good for gastropathy. Leaves are antiscorbutic, diuretic, anthelmintic,

astringent, expectorant and tonic. They are useful in asthma, bronchitis, cough,

strangury, painful tumors, constipation, verminosis and haemorrhoids. Shoots and

leaves are bitter and used in all types of poisons, cough and bronchitis. Fruits are

sweet, acrid, bitter, thermogenic, aphrodisiac, emollient, stomachic, purgative and

digestive. They are useful in constipation, flatulence and seminal weakness. Tender

twigs are used as toothbrush. The extract of the root is said to relive the pain due to

spleen troubles. Seed oil is applied on the skin in rheumatism. Used for centuries as a

natural toothbrush, its fibrous branches have been promoted by the World Health

Organization for oral hygiene use. Research suggests that it contains a number of

medically beneficial properties including abrasives, antiseptics, astringent, detergents,

enzyme inhibitors, and fluoride.

Functional uses

Food

Introduction 77

Fruits have a sweet, agreeable, aromatic, slightly pungent and peppery taste. They can

be eaten raw, cooked, or dried and stored. Fruit with or without seeds is said to

contain 1.7-1.86% sugars when ripe. Fermented drinks are also made from the fruit.

The leaf is somewhat bitter and aromatic, with a taste likened to mustard. The leaves

are also cooked as a sauce and eaten with couscous or as a green vegetable. Tender

shoots, seeds and seed oil are also edible. Edible salts are obtained from ashes.

Fodder: Leaves and young shoots are browsed by all stock, but normally cattle do not

occur in the driest part of the S. persica distribution range and hence it tends to be

valued more as a camel, sheep and goat forage. Leaves make good fodder as their

water content is high (15-36%). The high salt content of the leaves is said to affect the

taste of milk, but the leaves are said to increase lactation in cows. Apiculture: S.

persica is reported as a good source of nectar.

Fuel

The wood is sometimes used for firewood and charcoal. However, it is not used for

cooking meat, as it leaves a foul taste Services

Pests and diseases

When S. persica occurs on river terraces, it is a preferred host of Cistanche tubulosa,

an obligate phanerogamic root parasite. Defoliating larvae of several beetles attack the

tree, and leaves are often attacked by the lepidopteran Colotis ephiae. The mite

Eriophyes causes leaf gall. A number of fungi such as Cercospora udaipurensis,

Placosoma salvadorae and Sephogloeum salvadorae damage the leaves.

1.14.5 Salvadora oleiodes241-247

Salvadora oleiodes is a small bushy evergreen tree found in India and Pakistan and

southern Iran. In Iran it is called Tuch. Common names in Indian subcontinent include

Vann, (Punjabi), Pilu (Hindi), and jar (Sindhi language), in Saraiki language in Saraiki

Wasib called jall.

Common names

Bahapilu, chootapilu, jhal, pilu

Scientific classification

Kingdom PlantaePhylum AngiospermsClass Magnoliopsida

Introduction 78

Order Brassicales

Family SalvadoraceaeGenus SalvadoraSpecies oleiodes

Fig. 1.5: Plant of Salvadora oleiods

Description

It is a small tree with drooping branches, rarely with proper bole or exceeding a height

of 20 feet and a girth of 3 feet. It is very common plant in arid tracts but becomes

scarce where rainfall conditions are better. It can withstand great soil salinity. It

produces new leaves during April, which on maturity become thick and leathery. The

tree coppices fairly well but regenerates freely by root suckers and natural layering. It

is, however, very slow growing but a dense growth is often formed around the parent

plant by root suckers and some natural seedlings. The plant provides a dense shade. It

is often lopped for camel and goat fodder.

Introduction 79

Fruit

Small greenish white flowers are produced in March-April. The fruit is yellow and

ripens in the months of May and June. It forms one of the main grazing sources for

livestock owned by local farmers. It is often dried and preserved in large quantities.

The seeds are spread by birds. The seedlings come up under the parent plant or under

other bushes and are somewhat frost-tender.

Habitat

The vann is commonly found in and around Sandal Bar, and is reserved for use as

grazing sources for local peasant villages. In addition, a number of trees have been

preserved to provide shade for cattle.

Wood

The vann is mostly non-woody and the small amount of wood that it has is soft, light,

and not particularly useful for any of wood's normal uses, notably building and heat.

When burnt, it leaves a large quantity of ash, which can then be boiled down into a

substance for treating mange in camels.

Botanic description

Salvadora oleoides is a shrub or small tree, attaining 6-9 m height under favourable

conditions; trunk short, often twisted or bent, up to 2 m in diameter; branches

drooping, numerous, stiff, often swollen at forks; bark grey or whitish-grey. Leaves

glaucous, linear-or ovate-lanceolate, coriaceous and somewhat fleshy, dark greenish-

yellow when young, grey when mature. Flowers sessile, greenish-white, minute in

paniculate spikes, often clustered; calyx cup-shaped, in 4 rounded, obtuse lobes. Fruit

a drupe, globose, about 6 cm in diameter, usually yellow when ripe, dark brown or red

when dry. Seeds greenish-yellow, about 3 mm in diameter. The generic name was

given in 1749 in honour of an apothecary of Barcelona, Juan Salvador y Bosca (1598-

1681), by Dr Laurent Garcin, botanist, traveller and plant collector.

Uses

It is used as stimulant and emmenagogue and used to relieve splenalgia and as tonic.

The sbark is good for gastropathy. Leaves are antiscorbutic, diuretic, anthelmintic,

astringent, expectorant and tonic. They are useful in asthma, bronchitis, cough,

strangury, painful tumors, constipation, verminosis and haemorrhoids. Shoots and

leaves are bitter and used in all types of poisons, cough and bronchitis. Fruits are

sweet, acrid, bitter, thermogenic, aphrodisiac, emollient, stomachic, purgative and

Introduction 80

digestive. They are useful in constipation, flatulence and seminal weakness. Tender

twigs are used as toothbrush.