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Anti-inflammatory and Analgesic Activity of Morinda citrifolia (Noni) in Experimental Animals Dr. D. N. Srivastava Professor and Head, Pharmacology (Retd.) Chairman, Noni Experimental Research Program World Noni Research Foundation Hyderabad o o “ Man enters the world in pain, usually leaves it in pain, and spends more of the intervening time in pain than he would wish. Banishment of this imminent spectra has been a primary goal of magic rites and folk medicine since time unrecorded, long before advent of such intellectualised endeavors as specific therapies ” Henry B. Murphree (1971) For Screening the medicinal plant for their pharmacological and therapeutic activity it must follow Synthesis structure elucidation Medicinal Plant Extract Bioassay Separation Pure constituent Bioassay Toxicology Structure modification Bioassay Contents of Noni Noni contains Vitamins- Vit A, B, C, and D Minerals Carbohydrates Isolated nutraceuticals Aminoacids Parts of Noni plant used in treatment of inflammatory diseases Leaves • • • • • • • Juice of leaves can internally help gout, gingivitis and sties Tea used to treat fever Chewing leaves may smooth sore throat Leaf extracts were used to prevent clots Powdered leaves administered to skin for burns, boils and wounds Heated leaves used to treat joints Fresh crushed leaves are rubbed on chest to relieve chest pain and cold Contd… Root used to relieve pain, reduce fever and congestion internally Topically is used to treat joint swelling and gout Fruit Fruit given internally for gingivitis, bronchitis, arthritis, rheumatism and infection Mashed unripe fruits are applied to swollen areas, deep wound, boils, broken bone and inflammed joints COX enzymes COX-1 enzyme COX-2enzyme Responsible for protecting Responsible for body’s stomach lining and causing pain and kidneys inflammation NSAIDs Inhibit COX-1 enzyme Inhibit prostaglandin that Protect the stomach lining Gastric ulceration and colitis COX-2enzyme Inhibit prostaglandin that causes pain & inflammation anti-inflammatory & analgesic action COX-1 enzyme Not effected NONI inhibit COX-2 enzyme Allow COX-1 enzyme To continue functioning Inhibit PG that cause pain and inflammation Anti-inflammatory and analgesic action Role of Spolectin in pain and inflammation Isolation of scopolectin from Noni in 1993 by university of Hawaii, attribute the new compound to lowering BP, reducing inflammation, killing bacteria and fungi preventing tomour growth Spolectin is an important chemical required by body for smooth joint movement Spolectin is also antihistaminic It is also analgesic and antipyretic Spolectin have been found 5 times more effective than aspirin Significant analgesic of noni in mice on hot plate was demonstrated in a laboratory in France Immunomodulatory action of Noni and inflammation Noni stimulates the production of T cells in the immune system that play a pivotal role in fighting diseases Noni acts to enhance immune system involving macrophages and/or lymphocytes which are vital part of natural defence of body Noni has been shown to combat many types of bacteria Noni improves effectiveness of enzyme and enhances cellular communication. There was 5 health condition associated with immune system 1. Infection 2. Allergy 3. Autoimmune diseases 4. Cancer 5. Inflammation Auto-immune disorders Inflammation Antioxidant action of Noni and inflammation Many chronic and degenrative diseases including ageing, inflammatory diseases and many immune disorders are believed to be result of accumulated damage caused by free redicals Noni has a group of antioxidant which was ability to scavange free radicals which is many times stronger than other antioxidants These action increase integrity of the vascular system decreasing capillary permeability and fragibility Noni is particularly useful in phlebitis, arthritis, allergies. Further Noni augment wound healing, curb inflammation and hasten recovery from injuries and inhibit microbes causing infection Xeronine and pain inflammation Some of the reported physiological reponses from xeronine include • • • • • Releives arthritis Helps to heal sprain Decrease pain Eliminate injuries to mend Promotes injuries to mend Xeronine acts as the bodys supreme pain killer because it works with Endorphins in the body to numb pain and produce feeling of Euphoria. Without xeronine the Endoephin is useless Noni has been found to be 75% as effective as Morphine in relieving pain without side effects of Morphine. Unlike Morphine Noni is not addictive Sterols and inflammation Sterols and natural alcohols found in animals and plants The plant sterols are known as phytosterols Noni contains – (Beta) Sitosterols Stigmasterols Campesterol In animal study, beta-sitosterol has been shown to be anti-inflammatory and antipyretic Beta-sitosterol can regulate immune system and can improve arthritis, allergies and auto-immune diseases Anti-inflammatory activity in experimental animals Method : Carrageenin induced rat paw oedema Inflammogenic substances : Carrageenin Dose of Carrageenin : 0.1 ml/rat (1% solution) injected in planter aponeurosis of the hind paw Experimental animal : Rat Reference : Method described by Winter et al. (1962). Paw volume was measured by method of Bhatt et al. (1977) Percent anti-inflammatory activity = (1-T/C)× 100 where, T= Mean volume of oedema in drug treated group C= Mean volume of oedema in control group Anti-inflammatory activity in experimental animals Method : Cotton Pellet Implantation method Inflammogenic substance : Cotton wool Cotton Pellet : The sterilized pellets of cotton wool weighing 10 mg is implanted S/C in both groins of each rat Experimental animal : Rat Reference : Method described by Meier et al. (1950) Percent anti-inflammatory acitvity = (1 – T/C) × 100 where, T = Mean weight of granulation tissue in drug treated group C = Mean weight of granulation tissue in control group Analgesic activity in experimental animals Method : Hot Plate method Instrument : Hot plate analgesiometer heated at 55 + 0.5 0 C Experimental animal : Rat Reference : Curzon et al. (1980) Percent analgesic score (PAS) = T2/T1 × 100 where, T1= Reaction time (in second) before drug administration T2 = Reaction time (in seconds) after drug administration Analgesic activity in experimental animals Method : Rat tail hot wire method Instrument : Techno analgesiometer Experimental animal : Rat Reference : Davies et al. (1946) Percent analgesic score (PAS) = T2/T1 × 100 where, T1 = Reaction time (in seconds) before drug administration T2 = Reaction time (in seconds) after drug administration Conclusion Morinda Citrifolia, Noni has been reported to possess anti-inflammatory and analgesic activity on acute and chronic inflammatory reaction. Noni selectively inhibits COX-2 enzyme while allowing COX-1 enzyme1 to continue functioning. Scopoletin has been reported to produce anti-inflammatory, analgesic, antipyretic and antihistaminic activity . Noni helps in reducing inflammation, autoimmune diseases and infection by modifying the immune system of the body. The antioxidant activity of Noni curb inflammation and hasten recovery from injuries and inhibit microbes from causing infection. Xeronine works with Endorphine in the body and numb pain. Beta –sitosterol has been shown to produce anti-inflammatory and antipyretic activity. It may regulate immune system and improve rheumatoid arthritis, allergies, auto-immune diseases.