© 2018 jetir december 2018, volume 5, issue 12 an overview

© 2018 JETIR December 2018, Volume 5, Issue 12 www.jetir.org (ISSN-2349-5162)

JETIRDT06002 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 5

An Overview on Therapeutic Potential of

Azadirachta indica

Prajwal Chaguthi, Amit Mittal, Saurabh Singh, Dileep Singh Baghel*

School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar - Delhi G.T. Road,

Phagwara, Punjab (India)-14441

ABSTRACT

Herbs are valuable source of novel drugs that based on various phytochemicals present in it. Moreover,

they also a good source of nutraceuticals, food supplements, pharmaceutical intermediates. The side-

effects of modern medicine and highly development drug resistance have built up trust on medicinal

plants for herbal cure against the dangerous and infectious diseases. Azadirachta indica which also

known by the name of margosa tree is evergreen, broad leaved tree. intermediates. Azadirachta indica

derived from Persian word azad, dirakt, i-hind which means free tree of India. Each plant part of the

Neem belongs to the Meliaceae family has various therapeutic property so commercially exploitable; it

acquires the wide range of pharmacological action i.e. anti-inflammatory, antidiabetic, spermicidal, anti-

bacterial, mosquito-repellent activity, anti-allergic, anthelminthic, antidermatic, analgesic, antiulcer,

anti-viral, antifungal, insecticidal, anti-malarial, larvicidal, antioxidant. It is a one the unique herb

provides the solutions for hundreds to thousands concerns facing mankind.

Key word: Azadirachta indica, Ayurveda, Phytochemicals, Therapeutic potential, Neem, Nimba

INTRODUCTION

The ‘NEEM’ word is originating from Sanskrit word ‘nimba’ that means ‘helper of good health’. It is

also known as sarva roga nibarini, that means ‘one that cures all disease and disorder’ [1]. Some

scholars believe that was derived from Persian word azad, direct, i-hind which denotes free tree of India

[2]. Neem or Margosa also called the Indian lilac. It comes under Meliaceae family. It is also known as

ravishamba which literally means sunray like effects in providing health [3].

Neem is evergreen, an attractive broad-leaved tree which grows in tropical as well as in semi-tropical

regions. It acquires the wide range of pharmacological action i.e. anti-inflammatory, antidiabetic, anti-

bacterial, spermicidal, anti-allergic, antielminthic, anti-dermatic, analgesic, antiulcer, antimalarial,

antifungal, antiviral, insecticidal, larvicidal, antioxidant, anti-tumour etc. it is one of the wonder

medicine provides the solutions for hundreds to thousand concerns facing mankind [4, 5]. Neem tree has

some medicinal property in each part of plant. Generally, leaf, stem bark, fruit have high

pharmacological activity compared to other parts. Except that seed, root, flowers are also use for

different type of skin problem [4, 5].

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HISTORICAL BACKGROUND

Neem is one of the useful plant mentioned in Ayurvedic literature since ancient era. Formulations

prepared from neem have been used in India since thousands of years because of its antidiabetic,

anthelmintic, antiviral, antibacterial, antifungal, contraceptive, sedative etc. properties. In ancient times,

our forefather used neem tree as a cure for all type diseases, most of the people planted neem trees in

their homes. Issues like skin ailments, digestion issues, injuries, cleaning purpose, pesticides for crops

and many other daily problems [6].

“Nimba” is evergreen tree gives the feeling of heaven with its cooling shade in sunlight and its heat. It

also known by the name of divine tree, life offering tree, nature’s drug store and village pharmacy [7].

DESCRIPTION

Neem is one of the fast growing and multipurpose medium sized tree, that can reach height upto 30m,

with wide spread branches. It is generally evergreen but occasionally shed its leaves during winter

season. It has a deep taproot and grey coloured bark which gets fissured and flakes in old. A sticky,

browny orange exudates from old trees trunk in humid climates.

The leaves of neem are alternate, petiolated, at the end of branches it is clustur, unsimilar pinnate,

glabrous and dark green when mature, 18-42 cm in length and having 8-20 leaflets. The leaflets are 6-

12cm in length and 2-4cm in wide, marginally denticulated.

Starting of summer, the tree is usually covered by delightful white colours of flowers. The flowers are

numerous, aromatic and they are commonly more or less drooping panicles which are around 20 cm in

length.

Neem fruits are spherical, smooth, green in unripe changing to yellow to brown when mature. They have

a bitter taste and 1-2 cm diameter in size with a skiny epicarp, a mucilaginous fleshy mesocarp and a

strong endocarp. It consists of a number of ovoid oil seeds having 1-2 cm diameter. Oil is collected by

compressing kernel in the compressor. It normally starts produce fruit from three to four years. [8]

Figure 1: Neem tree

Figure 2: Neem leaves




Figure 3: Neem flowers

Figure 4: Neem fruits

Microscopical description

Leaf

Thin walls of epidermis on surface of Lamina is built. Externally, thick cuticle layered the tangentially

elongated cells. On lower surface, Anomocytic stomata is present. Parenchyma layered are composed in

thin walled cell which is cross by a multiple numbers of veins.In a few cells, calcium oxalate crystals are

found.

The two side of midrib covered by epidermis externally with thick cuticle showing biconvex outline.

Collenchyma is present down to epidermis with 3-5 layer. Stele are consisting of vascular bundle. The

remaining of tissues composes of tiny thin walled, parenchymatous cells with crystals of calcium

oxalate. Phloem is enclosed by fibre strand.

Bark

Neem stem bark is hard, woody consist of completely dead components of secondary phloem, with

intermittent tangential bands of pressed tissue(cork). It consists of different layers of cells known as

stone cell appear on continually arranged groups which is combined with the collapsed phloem

components. Four to six layers of fibre sets with Stem bark, the woody and tough piece of nimb

composed of phloem, cork tissue, stone cells, fibres groups etc. are present between the successive

zones of cork tissue.

Powder – It is green in colour. It consists of vessels, calcium oxalate crystals, particle of spongy, fibres

and parenchyma. [9]

Description of Neem in Ayurvedic text

The details of various opinions regarding gana/varga mentioned by ancient scholar is tabulated as below

S.N Name of text book Varga/gana

1. Dravyaguna vijyanam by priyabat

sharma [11]

Kusthaghan varga

2. Charak Samhita [10] Kandughana gana. and also mention in saka

varga

3. Astanga sangraha [10] Aragvadadi, guduchyadi and lakshadi varga

4. Sushrut Samhita [10] Aragvadadi, guduchyadi and lakshadi varga

5. Dhanwantari Nighantu [11] Kandughana gana

6. Bhavprakash Nighantu [12] Guduchyadi varga and kusthaghana dravya

7. Kaidev Nighantu [13] Krimighana and vranaghan varga




8. Preeya Nighantu [14] Haritakyadi varga

9. The Ayurvedic Pharmacopoeia of

India [9]

Neem consists of dry leaf and hard stem bark

of Azadirachta indica. (Fam. Meliaceae)

Neem formulation according to various ayurvedic texts

Name Medicinal use Parts

use

Dose References

Tiktaka ghrita Trisna, bhrama,

ganda, unmade, meda,

kamala, arsa, rakta

pitta, gulma, kustha

etc.

Stem

bark

12gm Astangahridaya: Cikitsasthana,

Adhyaaya 19; 2-4[14]

Aragvadhadi

Kwatha Curna

Vamana, visa vikara,

kapha dosha,

madhumeha, kandu,

vrana, Kustha

Stem

bark

48 gm

Astangahridaya: Sutrasthana,

Adhyaya 15; 17[14]

Nimbadi

Kwatha Curna

Kapha jvara, jvara Stem

bark

48 gm Cakradatta: Jvaracikitsa: 101[15]

Brhanmanjisth

adi Kwatha

Curna

Vatarakta, kustha,

upadamsa, ardita,

paksaghata,

stambhata,

medoroga, netradosha

Stem

bark

48 gm Sarngadharasamhita:

Madhyamakhanda: Adhyaya 2; 137

– 141[16]

Kasisadi Ghrita Sukradosha,

Vicarcika, visarpa,

kustha, visphota,

sukradosa, vatarakta,

upadamsa, nadivrana,

vrana, sotha,

bhagandara, arsa

Leaf - Sarngadharasamhita,

Madhayamakhanda, Adhyaya 9; 51-

541/2 [16]

Pancatikta

Guggulu Ghrita

Sandhigata

vatabyadhi, astigata

vata, majjagata vata,

pinasa, kustha, arbud

roga, pandu roga,

mada, gandamala,

nadivrana, aruchi,

guda bikar, kasa,

svasa, sotha,

hridroga, vatarakta,

rajyaksma,

bhagandara

Bark

12 gm Astangahridaya: Cikitsasthana,

Adhyaya 21; 57 - 581/2 [14]

Jatyadi Taila Kandu, sphotaka,

nadivrana, sastra-

vrana, dagdha-

varana, danta-roga,

nakha ksata

Leaf - Sarngadharasamhita,

Madhayamakhanda, Adhyaya 9;

168-170[16]

Maha

Visagarbha

Taila

Vatavyadhi roga,

gradhrasi, dantaroga,

sarvanga grahana,

karna nada, sparsa

Bark

_ Bhaisajyaratnavali:

Vatavyadhyadhikara; 414-421[17]

Vajraka Taila Tvagdosa,

dustanadivrana,

kustha

Stem

bark

- Astangahrdaya: Cikitsasthana,

Adhyaya 19;79-80[14]

Siva Gutika Panduroga, Stem 6 gm Yogaratnakara: Rajayaksmadhikara;




(Laghu) kustharoga,

bishamjvara, arsa,

bhagandara,

mutrakricchra,

yaksma, madhumeha,

pliharoga

bark 1 – 6[18]

CHEMICAL CONSTITUENTS

Azadirachta indica have loaded sources of several variety of ingredients that shows the therapeutic

effect. About sixty different constituents were isolated from neem leaf and most of them are chemically

characterized. Among them 35 are biologically active compounds. Among of them some vital active

constituents are azadirachtin, nimbolinin, nimbidin, gedunin, nimbidol, quercetin, nimbin, sodium

nimbinate, galic acid, salannin, etc. Leaves of neem have ingredients like nimbin, nimbanene,

hyperoside, kaempferol, myricetin, chlorogenic acid, scopoletin, valasinin, nimbandiol, nibiol, zafaral,

nimbolide, 17-hydroxyazadiradione, ascorbic acid and amino acid, 6-desacetylnimibinene, 7-desacetyl-

7-benzoylazadiradione, n- hexacosanol etc. Nimbin is isolated by indian chemists as a bitter pain

reliever from neem oil and later crystalized from neem leaf. [7,19]

Nimbin

Gallic acid

Quercetin




Pharmacological activities of different parts of neem according to chemical constituents

Part used Biological activity Neem compound

Bark Immunomodulatory and anti-inflammatory

[20]

Gallic acid

Catechin

Epicatechin

Antibacterial [21] Margolone

Margolonone

isomargolonone

Antitumour [22] Polysaccharides GI(a) and

GI(b)

Anti-inflammatory[22] Polysaccharides GII(a) and

GIII(a)

Immunomodulatory [23] NB-II peptidoglycan

Anti-acid secretory and antiulcer[23-24] Glycoside

Leaves Antifungal [25] Cyclic trisulphide

Tetra sulphide

Hyperglycemic [26] Quercetin

Antipyretic [27] Methanolic extract

Seed oil [28-

33]

Anti-inglammotory, anti-arthritic,

spermicidal, anti-fungal,anti-bacterial and

anti-pyretic

Nimbidine

Anti-bacterial, spermicidal and anti-malerial Nimbine

Anti- bacterial and anti-malerial Nimbolide

Anti-feedent and anti-malarial Azadirachtin

Anti-bacterial Mahmoodin

Fruit [34] Anti-ulcer Phytosterol

PHARMACOLOGICAL PROPERTY AND THEIR MECHANISM OF ACTION

Antimicrobial

Different study shows neem constituent have essential character which inhibit growth of microorganism.

It has a potentiality of cell wall breakdown of different types of bacteria. An extract of neem leaf shown

greater zones of inhibition compare to 3 percent sodium hypochlorite that they have an antimicrobial

activities.

The mixture of neem and guava extract have compounds containing antibacterial activity which is

potentially beneficial to control spoilage organism and foodborne microorganism. Different twenty-one

strains of microorganism were evaluated in study.




Another study of the different part of azadirachta indica on bacteria results shows the extracts of bark

and leaf has antibacterial activity against many types of bacteria. Extract of ethanol of neem leaf have in

vitro antibacterial activity over bacteria MRSA (methicillin resistant staphylococcus aureus) and the

staphylococcus aureus with greatest zone of inhibiting [32-34].

Antioxidant

All part of Neem shows an essential role in diseases control and prevention due to their antioxidant

property. [5] It function as free radical scavenging properties – leaf, flower, root bark and stem bark

extract. Taking a dose of nimbolide and azadirachtin, constituent present in neem inhibited the

increasement of DMBA, with control of procarcinogen stimulation as well as oxidative DNA loss and

upregulate of antioxidant and carcinogen detoxifying enzymes.

Extracts from neem leaf, flower and bark hold high antioxidant activity. Ethanol extracts of flower and

oil of seed were found to have better free radical-scavenging action. The free radical neutralization

activity is one of essential steps in disease control. The free radicals are deactivated or stabilize by

antioxidant, previously than it attack targets in biological cells. In activation of the antioxidative

enzyme, it plays important role that control of destruction cause by reactive oxygen species or free

radicles [35-37].

Anti-inflammatory

Numerous constituents of neem have anti-inflammatory properties. A research has shown that the dose

of 200mg/kg of neem leaves extract have anti-inflammatory activity by controlling proinflammatory

enzyme activities include (COX)cyclooxygenase, and (LOX)lipoxygenase enzyme. Chemical

constituents nimbidin suppresses the activity of macrophages and neutrophils related to inflammation.

Neem bark and seed oil also showed the anti-inflammatory effect. [38]

Anti-diabetic

Neem have important antidiabetic properties and have potential sources for prevent and treatment of

diabetes. Study shown that 70% of root bark extract significantly decrease the level of sugar in

800mg/kg dose [39]. Next experiment of neem proved that a dose of 250mg/kg decreased glucose levels

in fifteenth day [40]. Chloroform extract and methanolic extract indicate an excellent oral glucose

tolerance and decreased the glucosidase activity in intestine. [41]

Antiviral

An extract of neem bark at a dose of 40-100 μg/ml play vital role to stopped HSV-1 enter to cells. It also

has work against coxsackie virus B-4.

Extract of bark at a dose of 5.6mg/ml shown the antiviral action against the entire concentration range of

velogeni newcastle virus [42-43].

Antifungal

South local communities use neem leaf paste as ethno veterinary application for skin infections

including fungal, in small ruminants. Studies have claimed that alcohol and water extract of leaf

inhibited the development of different types of fungus. Extract of water, ethanol and ethyl acetate of

leaves inhibited development of some microbes such as Candida albicans, dermatophytes, Tania




versicolor, Tania corporis, Aspergillus fumigates, A. flavus, Aspergillus niger, Aspergillus terreus,

Cladosporium etc [19].

Anti-cancer

Cancer is one of the major and serious health problems which cause by modification of molecular or

genetic pathways result as development of cancer. The chemical constituents like flavonoid present in

neem show an action on inhibition of cancer growth.

Neem extracts possess ability to decrease or remove cancerous phenotype commonly termed as nasoor.

Ingredient of neem have an impressive quality in the care of cancer. It works by the regulation of the

cell signalling pathways. Nimb alter the action of various tumour suppressor genes like p(53), p(TEN),

angiogenesis like VEGF, transcription factors like NF-kB, and apoptosis like bcl2, bax. p-53 is genes

having a quality of inhibition of the growth of unnatural cells and the gene pTEN generally lost by

mutations in different type of primary as well as metastatic cancer. A study proved the treatment by

neem leaf extract of ethanol enhance the expression of pTEN, that inhibits mammary tumorigeneses.

Based on the study it was considered neem have vital role in the alteration of different cell signalling

pathways. It holds several ingredients which stimulate the tumour suppressor genes and inactive action

of different genes causing cancer growth and progression [19,36,44-46].

Anti-nephrotoxicity effect

The study in rat result proved that the extract of neem is capable to save the kidney from oxidative injure

[47].

Hepatoprotective

The study proved that pre-treatment by azadarichtin A dose decreases the risk of hepatocellular necrosis

and it shows the level of high dose slightly restores the liver of rat to normal. Leaf extract of neem on

antitubuler medicine produce hepatotoxicity and resulting water extract of leaf considerably prevents

modify the levels of bilirubin concentration, blood protein, alanine aminotransferase concentration,

alkaline phosphatase in serum. [48-49]

Immunomodulatory effect

Infusion of neem leaves was tested on broiler chicks to investigate immunomodulatory effects which

recover antibody, development performance and gross return in 50ml/litre of pure drinking water [50].

In dentistry

It is one of the natural antibacterial agents. Ethanolic extract of Neem shows maximum effect against S.

mutans which cause a dental carry. Petroleum and chloroform extract indicate strong antimicrobial

activities over different microorganism like streptococcus salivarius, fusobacterium nucleatum which

cause dental caries. Chewing of the sticks also showed maximum antibacterial activity [51-52].

In ancient time, people use the stem of neem for brushing teeth to protect the oral cavity from different

disease like gingivitis, plaque etc. bark and neem extracts is very effective in gum and cavities

problems. Due to its antioxidant activities it is beneficial to boost immune react in gum and tissues of

mouth. [51]




Wound healing

Neem oil in the chronic, non-healing wounds show a wound healing activity and a significant reduction

in the longest diameter wounds has been observed. Based on the studies, the wound healing properties

of aqueous extracts of neem leaves are supposed to act biochemically through inflammatory response

and neovascularization. Current researchers have also established healing power of NLEs in different

wound models including significant wound healing in Sprague Dawley rats for excision and incision

wounds as well as increased neo-vascularisation promoting wound healing. [53]

Neem in other uses

Agriculture

Neem is widely use against leaf eating caterpillars, grubs, locusts and grasshoppers as bio-pesticide in

agriculture purposes and protect the seeds from different type of pest, Oil is generally used.

Neem play role to control different types of insect as a pesticide, as feeding deterrent, as an ovipositional

deterrent.

Neem oil are specially used as fungicide as a preventive and when fungus is just start. It covers the leaf

of crop in turns prevents the growth of the fungus. Neem oil is useful for different type of rots, grey

mildews, powdery mildew, leaf spots and blights.

Neem cake use as natural soil conditioner, typically contains 6 percent neem oil and NPK organic form

for plant growth. It contains sulphur as well as bitter limonoids which is harmless to earthworm, noted

earthworm populations are increased in plots treated with neem cake.

Kernel powder and neem oil are used to protects stored food crops from pathogens for upto 2 years. It

also prevents the proliferation of storage pest or insects if it has already affected the grains [54].

Soap

Generally, Neem oil is used by industries to manufacture soap. Although many of it goes to low scale

speciality soap. The raw oil is specially used to manufacture coarse laundry soaps. Almost colourless

and odourless products is use for high quality toilet and laundry soaps [55].

Cosmetics

Neem leaves powder widely use in facial cream as its perceived India as beauty aid. Pure neem oil is

used to prepare nail polish and other different cosmetics.

Lubricants

It is better than other vegetable oils to resist degradation because of non-drying character of oil. So, it is

use as in lubricant production [57].

CONCLUSION

Acceptance and Popularity of natural products or their derivatives significance is well known for

prevention and cure of the diseases in worldwide due to less side or adverse effects. Neem (Azadirachta

indica) is one of the most versatile medicinal plants, widely distributed in Indian subcontinent. Clinical

and pre-clinical based studies confirmed that neem plays pivotal role in prevention of various diseases.




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57. Chandan Sharma1, Ganipantapalli Shyam Sundar1, Harish Babu K1, Srinivas M Sitale1 Smitha B

S2, Experimental Study on The Use of Neem Oil as Lubricant in IC Engine, 2017


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