Anti-inflammatory and Anti-inflammatory and Analgesic Activity of Analgesic Activity of

Morinda citrifoliaMorinda citrifolia (Noni) in (Noni) in Experimental AnimalsExperimental Animals

Dr. D. N. SrivastavaDr. D. N. SrivastavaProfessor and Head, Pharmacology (Retd.)Professor and Head, Pharmacology (Retd.)

Chairman, Noni Experimental Research ProgramChairman, Noni Experimental Research ProgramWorld Noni Research FoundationWorld Noni Research Foundation

HyderabadHyderabad

o “ “ Man enters the world in pain, usually Man enters the world in pain, usually leaves it in pain, and spends more of the leaves it in pain, and spends more of the intervening time in pain than he would intervening time in pain than he would wish.wish.

o Banishment of this imminent spectra has Banishment of this imminent spectra has been a primary goal of magic rites and been a primary goal of magic rites and folk medicine since time unrecorded, long folk medicine since time unrecorded, long before advent of such intellectualised before advent of such intellectualised endeavors as specific therapies ”endeavors as specific therapies ”

Henry B. Murphree Henry B. Murphree (1971)(1971)

For Screening the medicinal plant for For Screening the medicinal plant for their pharmacological and therapeutic their pharmacological and therapeutic

activity it must followactivity it must follow SynthesisSynthesis

structure structure elucidationelucidation

Medicinal Plant

Extract

Separation Pure

constituent

Toxicology

Bioassay BioassayStructure modification

Bioassay

Contents of NoniContents of Noni Noni containsNoni contains Vitamins- Vit A, B, C, and D Vitamins- Vit A, B, C, and D MineralsMinerals CarbohydratesCarbohydrates Isolated nutraceuticalsIsolated nutraceuticals AminoacidsAminoacids

Parts of Noni plant used in Parts of Noni plant used in treatment of inflammatory treatment of inflammatory

diseasesdiseasesLeaves Leaves • Juice of leaves can internally help gout, Juice of leaves can internally help gout,

gingivitis and stiesgingivitis and sties• Tea used to treat feverTea used to treat fever• Chewing leaves may smooth sore throatChewing leaves may smooth sore throat• Leaf extracts were used to prevent clotsLeaf extracts were used to prevent clots• Powdered leaves administered to skin for Powdered leaves administered to skin for

burns, boils and woundsburns, boils and wounds• Heated leaves used to treat jointsHeated leaves used to treat joints• Fresh crushed leaves are rubbed on chest to Fresh crushed leaves are rubbed on chest to

relieverelieve chest pain and cold chest pain and cold

Contd…Contd…

RootRoot used to relieve pain, reduce fever and used to relieve pain, reduce fever and

congestion internallycongestion internally Topically is used to treat joint swelling and Topically is used to treat joint swelling and

goutgout

FruitFruit Fruit given internally for gingivitis, Fruit given internally for gingivitis,

bronchitis, arthritis, rheumatism and infectionbronchitis, arthritis, rheumatism and infection Mashed unripe fruits are applied to swollen Mashed unripe fruits are applied to swollen

areas, deep wound, boils, broken bone and areas, deep wound, boils, broken bone and inflammed inflammed joints joints

COX enzymesCOX enzymesCOX-1 enzyme COX-2enzymeCOX-1 enzyme COX-2enzyme Responsible for protecting Responsible Responsible for protecting Responsible

for for body’s stomach lining and causing body’s stomach lining and causing

pain andpain and kidneys inflammationkidneys inflammation

NSAIDsNSAIDsInhibitInhibit

COX-1 enzyme COX-2enzymeCOX-1 enzyme COX-2enzyme Inhibit prostaglandin that Inhibit prostaglandin Inhibit prostaglandin that Inhibit prostaglandin

thatthatProtect the stomach lining causes pain & Protect the stomach lining causes pain &

inflammationinflammation

Gastric ulceration and colitis anti-inflammatory & Gastric ulceration and colitis anti-inflammatory & analgesic actionanalgesic action

NONI inhibitNONI inhibitCOX-1 enzyme COX-2 enzymeCOX-1 enzyme COX-2 enzymeNot effectedNot effected

Allow COX-1 enzyme Inhibit PG that causeAllow COX-1 enzyme Inhibit PG that causeTo continue functioning pain and To continue functioning pain and

inflammationinflammation

Anti-inflammatory Anti-inflammatory and and

analgesic actionanalgesic action

Role of Spolectin in pain and Role of Spolectin in pain and inflammationinflammation Isolation of scopolectin from Noni in 1993 by Isolation of scopolectin from Noni in 1993 by

university of Hawaii, attribute the new compound university of Hawaii, attribute the new compound to lowering BP, reducing inflammation, killing to lowering BP, reducing inflammation, killing bacteria and fungi preventing tomour growthbacteria and fungi preventing tomour growth

Spolectin is an important chemical required by Spolectin is an important chemical required by body for smooth joint movementbody for smooth joint movement

Spolectin is also antihistaminicSpolectin is also antihistaminic It is also analgesic and antipyreticIt is also analgesic and antipyretic Spolectin have been found 5 times more effective Spolectin have been found 5 times more effective

than aspirinthan aspirin Significant analgesic of noni in mice on hot plate Significant analgesic of noni in mice on hot plate

was was demonstrated in a laboratory in Francedemonstrated in a laboratory in France

Immunomodulatory action Immunomodulatory action of Noni and inflammationof Noni and inflammation

Noni stimulates the production of T cells in the immune Noni stimulates the production of T cells in the immune system that play a pivotal role in fighting diseasessystem that play a pivotal role in fighting diseases

Noni acts to enhance immune system involving Noni acts to enhance immune system involving macrophages and/or lymphocytes which are vital part of macrophages and/or lymphocytes which are vital part of natural defence of bodynatural defence of body

Noni has been shown to combat many types of bacteriaNoni has been shown to combat many types of bacteria Noni improves effectiveness of enzyme and enhances Noni improves effectiveness of enzyme and enhances

cellular communication. There was 5 health condition cellular communication. There was 5 health condition associated with immune systemassociated with immune system

1. Infection 2. Allergy 3. Autoimmune diseases1. Infection 2. Allergy 3. Autoimmune diseases 4. Cancer 5. Inflammation4. Cancer 5. Inflammation Auto-immune disordersAuto-immune disorders InflammationInflammation

Antioxidant action of Noni Antioxidant action of Noni and inflammationand inflammation

Many chronic and degenrative diseases including Many chronic and degenrative diseases including ageing, inflammatory diseases and many immune ageing, inflammatory diseases and many immune disorders are believed to be result of accumulated disorders are believed to be result of accumulated damage caused by free redicalsdamage caused by free redicals

Noni has a group of antioxidant which was ability to Noni has a group of antioxidant which was ability to scavange free radicals which is many times stronger scavange free radicals which is many times stronger than other antioxidantsthan other antioxidants

These action increase integrity of the vascular These action increase integrity of the vascular system decreasing capillary permeability and system decreasing capillary permeability and fragibilityfragibility

Noni is particularly useful in phlebitis, arthritis, Noni is particularly useful in phlebitis, arthritis, allergies. Further Noni augment wound healing, allergies. Further Noni augment wound healing, curb inflammation and hasten recovery from curb inflammation and hasten recovery from injuries and inhibit microbes causing infection injuries and inhibit microbes causing infection

Xeronine and pain Xeronine and pain inflammationinflammation Some of the reported physiological reponses from Some of the reported physiological reponses from

xeronine includexeronine include• Releives arthritisReleives arthritis• Helps to heal sprainHelps to heal sprain• Decrease painDecrease pain• Eliminate injuries to mendEliminate injuries to mend• Promotes injuries to mendPromotes injuries to mend

Xeronine acts as the bodys supreme pain killer Xeronine acts as the bodys supreme pain killer because it works with Endorphins in the body to because it works with Endorphins in the body to numb pain and produce feeling of Euphoria. numb pain and produce feeling of Euphoria. Without xeronine the Endoephin is uselessWithout xeronine the Endoephin is useless

Noni has been found to be 75% as effective as Noni has been found to be 75% as effective as Morphine in relieving pain without side effects of Morphine in relieving pain without side effects of

Morphine. Unlike Morphine Noni is notMorphine. Unlike Morphine Noni is not addictive addictive

Sterols and inflammationSterols and inflammation Sterols and natural alcohols found in animals and Sterols and natural alcohols found in animals and

plantsplants The plant sterols are known as phytosterolsThe plant sterols are known as phytosterols Noni contains – (Beta) SitosterolsNoni contains – (Beta) Sitosterols

StigmasterolsStigmasterols

CampesterolCampesterol In animal study, beta-sitosterol has been shown to In animal study, beta-sitosterol has been shown to

be anti-inflammatory and antipyreticbe anti-inflammatory and antipyretic Beta-sitosterol can regulate immune system and Beta-sitosterol can regulate immune system and

can improve arthritis, allergies and auto-immune can improve arthritis, allergies and auto-immune diseasesdiseases

Anti-inflammatory Anti-inflammatory activity in experimental activity in experimental

animalsanimals Method : Carrageenin induced rat paw oedemaMethod : Carrageenin induced rat paw oedema Inflammogenic substances : CarrageeninInflammogenic substances : Carrageenin Dose of Carrageenin : 0.1 ml/rat (1% solution) Dose of Carrageenin : 0.1 ml/rat (1% solution)

injected in planter aponeurosis of the hind pawinjected in planter aponeurosis of the hind paw Experimental animal : RatExperimental animal : Rat Reference : Method described by Winter Reference : Method described by Winter et al.et al.

(1962). Paw volume was measured by method of (1962). Paw volume was measured by method of Bhatt Bhatt et al.et al. (1977) (1977)

Percent anti-inflammatory activity = (1-T/C)× 100Percent anti-inflammatory activity = (1-T/C)× 100 where, T= Mean volume of oedema in drug where, T= Mean volume of oedema in drug

treated grouptreated group C= Mean volume of oedema in control C= Mean volume of oedema in control

groupgroup

Anti-inflammatory Anti-inflammatory activity in experimental activity in experimental

animalsanimals Method : Cotton Pellet Implantation methodMethod : Cotton Pellet Implantation method Inflammogenic substance : Cotton woolInflammogenic substance : Cotton wool Cotton Pellet : The sterilized pellets of cotton wool Cotton Pellet : The sterilized pellets of cotton wool

weighing 10 mg is implanted S/C in both groins of weighing 10 mg is implanted S/C in both groins of each rateach rat

Experimental animal : RatExperimental animal : Rat Reference : Method described by Meier et al. (1950)Reference : Method described by Meier et al. (1950) Percent anti-inflammatory acitvity = (1 – T/C) × 100Percent anti-inflammatory acitvity = (1 – T/C) × 100 where, T = Mean weight of granulation tissue in where, T = Mean weight of granulation tissue in

drug treated groupdrug treated group C = Mean weight of granulation tissue in C = Mean weight of granulation tissue in

control groupcontrol group

Analgesic activity in Analgesic activity in experimental animalsexperimental animals

Method : Hot Plate methodMethod : Hot Plate method Instrument : Hot plate analgesiometer Instrument : Hot plate analgesiometer

heated at 55 + 0.5heated at 55 + 0.5 0 0 CC Experimental animal : RatExperimental animal : Rat Reference : Curzon et al. (1980)Reference : Curzon et al. (1980) Percent analgesic score (PAS) = TPercent analgesic score (PAS) = T22/T/T1 1 × 100× 100

where, Twhere, T1= 1= Reaction time (in second) before Reaction time (in second) before drug administrationdrug administration

TT2 = Reaction time (in seconds) after drug administration2 = Reaction time (in seconds) after drug administration

Analgesic activity in Analgesic activity in experimental animalsexperimental animals

Method : Rat tail hot wire methodMethod : Rat tail hot wire method Instrument : Techno analgesiometerInstrument : Techno analgesiometer Experimental animal : RatExperimental animal : Rat Reference : Davies et al. (1946)Reference : Davies et al. (1946) Percent analgesic score (PAS) = TPercent analgesic score (PAS) = T22/T/T11 × ×

100100 where, where, T1 = Reaction time (in seconds) T1 = Reaction time (in seconds)

before drug administrationbefore drug administration T2 = Reaction time (in seconds) after T2 = Reaction time (in seconds) after

drug drug administrationadministration

ConclusionConclusion Morinda CitrifoliaMorinda Citrifolia, Noni has been reported to possess anti-, Noni has been reported to possess anti-

inflammatory and analgesic activity on acute and chronic inflammatory and analgesic activity on acute and chronic inflammatory reaction.inflammatory reaction.

Noni selectively inhibits COX-2 enzyme while allowing COX-1 Noni selectively inhibits COX-2 enzyme while allowing COX-1 enzyme1 to continue functioning.enzyme1 to continue functioning.

Scopoletin has been reported to produce anti-inflammatory, Scopoletin has been reported to produce anti-inflammatory, analgesic, antipyretic and antihistaminic activity .analgesic, antipyretic and antihistaminic activity .

Noni helps in reducing inflammation, autoimmune diseases and Noni helps in reducing inflammation, autoimmune diseases and infection by modifying the immune system of the body.infection by modifying the immune system of the body.

The antioxidant activity of Noni curb inflammation and hasten The antioxidant activity of Noni curb inflammation and hasten recovery from injuries and inhibit microbes from causing recovery from injuries and inhibit microbes from causing infection.infection.

Xeronine works with Endorphine in the body and numb pain.Xeronine works with Endorphine in the body and numb pain. Beta –sitosterol has been shown to produce anti-inflammatory and Beta –sitosterol has been shown to produce anti-inflammatory and

antipyretic activity. It may regulate immune system and improve antipyretic activity. It may regulate immune system and improve rheumatoid arthritis, allergies, auto-immune diseases. rheumatoid arthritis, allergies, auto-immune diseases.