Noni 5

Noni Clinical Research Journal
Volume 1 Numbers 1-2 January - July 2007
Editor-In-Chief Dr. Kirti Singh
Technical Editor P. Rethinam
World Noni Research Foundation

# 64, Third Cross Street, Second Main Road, Gandhi Nagar Adyar, Chennai - 600 020. India
E-mail : mail@worldnoni.org Visit : www.worldnoni.org
Noni Clinical Research Journal

Noni Clincial Research Journal, is an half-yearly publication of World Noni Research Foundation devoted to original Research and Development contributions in the field of Clinical Studies, Clinical Therapies and Clinical Strategies of Noni Research. Publication of paper in the journal automatically transfers the copy rights from the authors to the journal. The editor reserves the privilege of editing the manuscript and adding or deleting relevant parts to make it suitable for publication in the journal. Any part of the journal may be reproduced with the written permission of the Editor. Subscription per annum Rs. 500/-. Correspondence regarding subscriptions should be addressed to World Noni Research Foundation, 64, Third Cross Street, Second Main Road, Gandhi Nagar, Adyar, Chennai - 600 020, India
Communication Address : Noni Clinical Research Journal World Noni Research Foundation 64, Third Cross Street, Second Main Road, Gandhi Nagar, Adyar, Chennai - 600 020. E-mail : mail@worldnoni.org Visit : www.worldnoni.org
WNRF, 64, Third Cross Street, Second Main Road, Gandhi Nagar, Adyar, Chennai 600 020, India.
World Noni Research Foundation
Noni Research Clinical Journal

Volume 1 Number 1-2 January - July 2007 CONTENTS REVIEW
Editorial Board Editor-In-Chief Dr. Kirti Singh
Technical Editor P. Rethinam
1 17 22 25 31
Clinical Research on Morinda citrifolia L. Noni Prof. P. I. Peter
Members Dr. K. Mohandas Dr. N. Murugesh Dr. Sathish Kumar Dr. K. Pradhan Prof. P. I. Peter
The effect of Noni (Morinda citrifolia L.) in Type 2 diabetes mellitus in inadequately controlled patients
G. Sathish Kumar
Studies of Comparative Anti-HIV Activity and cytotoxicity of Morinda citrifolia L.

Periyasamy Selvam, Narayanan Murugesh and Myriam Witvrouw
Effects of Noni (Morinda citrifolia L.) on Carcinoma of Breast

Dr. Rangadhar Satapathy
Effect of Noni (Morinda citrifolia L.) on Filarial Worm Infestation In Vitro Study.
Price : Rs. 500 / annum US $ 20 / annum
34 38
Anti-fibrotic effect of Noni (Morinda citrifolia. L) on carbon tetrachloride induced liver fibrosis
N. Murugesh, A.J.M. Christina and N. Chidambaranathan
Disclaimer : The views expressed in the articles are the views of the authors and not the views of WNRF.
Uricosuric Effect of Indian Noni (Morinda citrifolia. L)
N. Murugesh
Prof. P. I. Peter
Clinical Research on Morinda citrifolia L. Noni
Authors affiliation : Prof. P. I. Peter 85, First Main Road Gandhi Nagar, Adyar Chennai - 600 020. India
Keywords : Morinda citrifolia, Xeronine, anti bacterial, antiviral, antitumor,
analgesic, anti-inflammatory, immune enhancing, cancer prevention.
Abstract : Morinda Citrifolia Noni family Rubiaceae has been widly used by the people and folk healers for food and other medicinal purposes. Traditional medical manuscripts handed down from generation to generation cite the Noni fruit as the primary ingredient in their health preparation. Decades of ground breaking research reveals a broad range of therapeutic effects, including anti bacterial, antiviral, antitumor, anti helmin, analgesic, hypotensive, anti-inflammatory, immune enhancing and cancer prevention activities. In order to encapsulate the medicinal value and therapeutic effects of the Noni fruit and to summarize scientific evidence that supports the traditional claims a literature review and recent advances in Noni research has been detailed.
Introduction
Morinda citrifolia L., is commonly known as Great morinda, Indian mulberry, Beach mulberry and the (noni) fruit has been used in tropical regions as both Prof. P. I. Peter food and folk medicine. The recent use of noni as a dietary supplement has 85, First Main Road Gandhi Nagar, Adyar increased greatly and is reported to have a broad range of therapeutic effects, Chennai - 600 020. India including antibacterial, antiviral, antifungal, antitumor, anthelminthetic, analgesic, E-mail : chairman@nonifamily.net hypotensive, anti-inflammatory, and immune enhancing effects. Morinda citrifolia ,L., is native to South East Asia but has been extensively spread by man throughout India and into the Pacific islands as far as the islands of French Polynesia, of which Tahiti is the most prominent. It can also be found in parts of West Indies . Noni is a valuable medicinal plant and the recent discoveries about Noni, looks bright for this plant, but further studies has to be performed to discover its full potential.
Correspondence to :
In order to reveal the nutritional and medicinal value of the Noni plant, and to summarize scientific evidence that supports the claim, a literature review and recent advances in Noni research are given below.
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Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni
Pharmacological activity of the active principles in Noni

The presence of phytonutrients and vitamins in Noni can help the body fight microbes, help fight against inflammation, help fight carcinogens, and boost the immune system. The Pharmacological activity of the active principles being : Oligo- and polysaccharides long-chain sugar molecules that serve a probiotic function as dietary fiber fermentable by colonic bacteria, yielding short chain fatty acids with numerous potential health properties . Glycosides sugar-phenolic compounds including flavonoids such as rutin and asperulosidic acid, are common in several Rubiaceae plants; specifically named noni isolates called iridoides and morindoides have been reported. Trisaccharide fatty-acid esters, noniosides - resulting from combination of an alcohol and an acid in noni fruit, noniosides are chemicals giving noni its noxious smell and taste. Scopoletin may have antibiotic activities; research is preliminary. Beta-sitosterol a plant sterol with potential for anti-cholesterol activity. Damnacanthal an anthraquinone having potential as an inhibitor of HIV viral proteins. Alkaloids naturally occurring amines from plants, often attributed to causing bitter tastes and so may contribute to the foul taste of noni. Some references mention xeronine or proxeronine as important noni constituents. Other components being octoanoic acid, potassium, vitamin C, terpenoids, alkaloids, anthraquinones (such as nordamnacanthal, morindone, rubiadin, and rubiadin,methyl ether, anthraquinone glycoside), carotene, vitamin A, flavone glycosides, linoleic acid, Alizarin, amino acids, acubin, L-asperuloside, caproic acid, caprylic acid, ursolic acid, rutin, and a putative proxeronine. Xeronine system: Noni fruit contains a natural precursor for Xeronine that was named Proxeronine. Proxeronine is converted to the alkaloid, Xeronine, in the body by an enzyme called Proxeroninase. Xeronine is able to modify the molecular structure of proteins. Thus Xeronine has a wide range of biological activities. Xeronine will interact with the protein and make it fold into its proper conformation.
Pharmacological Studies and medicinal uses

Noni is used by some cancer patients for its anti-cancer and tumor-reducing possibilities. Some sufferers from immune-compromised diseases such as AIDS
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and chronic fatigue syndrome use Noni to boost immune system function. In research conducted on mice, Noni has been shown to boost the immune system directly by increasing the activity of macrophages and or lymphocytes in the immune system. In recent studies, the polysaccharides in Noni have shown to exhibit an anti-tumor effect and when taken in conjunction with chemotherapeutic agents it can help improve recovery time. People with diabetes and hypoglycemia have reported that noni helps stabilize blood sugar levels in the body. People with arthritis, joint pain, and inflammatory conditions have used noni. It is also used as a sedative, painkiller, and sleeping aid. Noni juice is recommended to remove parasites, to cleanse the digestive tract and improve digestion, and to control weight. It is used as a general health tonic to improve energy and resistance and to slow the effects of aging. It is also used for asthma; digestive disorders including ulcers; irritable bowel syndrome; constipation and diarrhea; and fibromyalgia, a condition characterized by fatigue and chronic pain. Noni has been traditionally used as an analgesic pain reliever and sedative. Researchers recently put this to the test with mice in an experiment and found that in fact Noni did demonstrate a non-toxic analgesic pain relieving effect and sedative effect on the mice. The researchers findings did confirm the traditional analgesic properties and uses of the Noni plant.
Scientific Studies
A substance called ursolic acid found in the leaves of the noni plant has been shown to have anti-cancer properties in the body. A Japanese study found that noni fruit contains another substance (damnacanthal) that has some effectiveness against pre-cancerous cells. Some evidence points to nonis ability to increase immune system activity, due to substances found in the fruit (including a chemical called proxeronine). The leaves of the plant contain chemicals that may lower blood sugar levels, as well as reduce pain and inflammation. One study showed that laboratory mice with lung cancer had much longer survival times when given noni juice daily. A French study determined that the roots of the noni plant contain natural sedatives, while another study pointed to a compound that noni leaves may contain that is anti-malarial and anti-parasitic in its effects. Finally, surveys of noni users have indicated testimonial success with the use of noni for cancer, strokes, diabetes, and as a general health and energy improver. Noni has been shown to contain vitamins, minerals, and antioxidants.
Preliminary medical research

Over the years since 1994, noni has increasingly stimulated the interest of medical science, with 114 papers published since then and 36 just in 2006-7. Despite the
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large market for juice products and research developments, the nutrient and phytochemical profiles of noni have not been extensively studied. Furthermore, numerous health claims made in noni juice marketing are gradually supported by scientific research and in human clinical trials. One cancer study completed under NIH peer-review in 2006 has been conducted, the results of which remain unpublished as of August 2007. Likewise, in a university-based clinical trial funded by the noni juice manufacturer, Tahitian Noni International, Inc., it was shown that noni juice consumption lowered blood cholesterol levels. Completed in 2006, however, the results of this study have not been published under peer-review . Laboratory studies have investigated nonis effect on the growth of cancerous tissue in mice. One such study in vitro found that noni reduced growth of capillary vessels sprouting from human breast tumor explants and, at increased concentrations, caused existing vessels to degenerate. It remains unknown whether such effects occur in vivo in other animal models or in cancer patients. Another study showed noni juice to inhibit formation of cancer cells in rats (using detection methods of biochemical markers called DNA adducts). It further showed a reduced number of DNA adducts in rats induced with a carcinogen. The same study showed effective antioxidant properties of noni juice compared with those of vitamin C, grape seed powder, and pycnogenol. The results indicated reduced carcinogen-DNA adduct formation in this laboratory model and antioxidant activity that may be relevant to anti-cancer mechanisms.
Recent advances in Noni research- Biological activities of Noni

Antibacterial activity Acubin, L-asperuloside, and alizarin in the Noni fruit, as well as some other anthraquinone compounds in Noni roots, are all proven antibacterial agents. These compounds have been shown to fight against infectious bacteria strains such as Pseudomonas aeruginosa, Proteus morgaii, Staphylococcus aureus, Baciillis subtilis, Escherichia coli, Salmonella, and Shigela. These antibacterial elements within Noni are responsible for the treatment of skin infections, colds, fevers, and other bacterial-caused health problems Recently, Duncan demonstrated that scopoletin, a health promoter in Noni, inhibits the activity of E. coli, commonly associated with recent outbreaks resulting in hundreds of serious infections and even death. Noni also helps stomach ulcer through inhibition of the bacteria H pylori.
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Antiviral activity Umezawa and coworkers found a compound isolated from Noni roots named 1methoxy- 2-formyl-3-hydroxyanthraquinone suppressed the cytopathic effect of HIV infected MT-4 cells, without inhibiting cell growth. Anthelmintic activity An ethanol extract of the tender Noni leaves induced paralysis and death of the human parasitic nematode worm, Ascaris Lumbricoides, within a day. A botanist via Morton reported that Noni has been used in the Philippines and Hawaii as an effective insecticide.
Analgesic activity
Joseph Betz reported that the Noni fruits possesses analgesic and tranquilizing activities. A French research team led by Younos, tested the analgesic and sedative effects of extracts from the Morinda citrifolia plant. The extract did show a significant, dose-related, central analgesic activity in the treated mice. They stated that these findings validate the traditional analgesic properties of this plant. The analgesic efficacy of the Noni extract is 75 % as strong as morphine, yet nonaddictive and side effect free. In cooperation between University of Illinois College of Medicine and Henan Medical University, Wang and Fu examined the analgesic properties of noni in animal models. NONI was tested for its analgesic properties by the twisted method animal model. Hypotensive activity Dang Van Ho of Vietnam demonstrated that a total extract of the Noni roots has a hypotensive effect. Moorthy and coworkers found that an ethanol extract of the Noni roots lowered the blood pressure in an anesthetized dog. Youngkens research team determined that a hot water extract of Noni roots lowered the blood pressure of an anesthetized dog. A Hawaiian physician reported that Noni fruit juice had a diuretic effect. Immunological activity Asahina found that an alcohol extract of Noni fruit at various concentrations inhibited the production of tumor necrosis factor-alpha (TNF-a), which is an endogenous tumor promoters. Therefore the alcohol extract may inhibit the tumor promoting effect of TNF-a. Hirazumi found that noni contains a polysacchariderich substance that inhibited tumor growth. It did not exert significant cytotoxic effects in adapted cultures of lung cancer cells, but could activate peritoneal exudates cells to impart profound toxicity when co-cultured with the tumor cells.
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Mental health and improved high frequency

A small human clinical trial of the effect of Noni on auditory function and quality of life in the patients with decreased bone mineral density and auditory function has been conducted in UIC College of Medicine, Rockford, IL. This study showed that Noni provided a positive benefit on mental health and improved high frequency hearing. The data suggests that increased amounts or extended duration of Noni intake may be required to affect this disorder.
Anti-inflammatory activity
Selective inhibition of COX-2 activity of Noni. Accumulating evidence indicates that COX-2 inhibitors may be involved in breast, colon, and lung cancer development. Interest in cancer chemoprevention with COX-2 inhibitors has been stimulated by epidemiological observations that the use of aspirin and other non-steroidal inflammatory drugs (NSAIDs) is associated with the reduced incidence of colon and breast cancer. The main target of NSAID activity is the cyclooxygenase (COX) enzyme. Two isoforms of COX have been identified: COX-1, the constitutive isoform, and COX-2, the inducible form of the enzyme. COX-2 can undergo rapid induction in response to chemical carcinogens. It has been suggested that COX-2 over expression may lead to increased angiogenesis and inflammatory reaction. Therefore the inhibition of COX-2 might have a general cancer preventive effect via anti-inflammatory activity and decrease angiogenesis. In this study, the selectivity of COX-2 inhibition of Noni versus COX-1 in vitro was investigated. The discovery of the selective COX-2 inhibition of Noni is very significant since Noni is a natural fruit juice without side effects. This is the first scientific evidence for a strong antiinflammatory activity in Noni, which may also be one mechanism of cancer prevention.
Cancer Preventive Effect of Morinda citrifolia (Noni)

The hypothesis that Morinda citrifolia ,L possesses a cancer preventive effect at the initiation stage of carcinogenesis was studied. One preliminary data indicated that 10% Noni Juice made from Morinda citrifolia fruit in drinking water for one week was able to prevent DMBA-DNA adduct formation. The levels of DMBA-DNA adducts were reduced by 30% in the heart, 41% in the lung, 42% in the liver, and 80% in the kidney of female SD rats. Even more dramatic results were obtained in male C57 BL-6 mice: 10% noni was able to reduce DMBA-DNA adduct formation by 60% in the heart, 50% in the lung, 70% in the liver, and 90% in the kidney. In order to explore the mechanism of this preventive effect, the antioxidant activity of
9 Noni Cli. Res. J. 2007, 1(1-2)
Noni was examined in vitro by lipid hydro peroxide (LPO) and Tetrazolium nitroblue (TNB) assays. The results suggest that prevention of carcinogen-DNA adduct formation and the antioxidant activity of noni may contribute to the cancer preventive effect of Morinda citrifolia L.
Conclusions
Ancient folk healers used M citrifolia as one of their primary medicinal plants. As folk traditions have been blended with introduced cash economies, modified medicinal systems have evolved. These systems are based upon both commercialized healers and commercialized plant-based remedies. Elements that have contributed to the commercialization of M.citrifolia ,L., includes., key publications and technological introductions from other cultures, and shifts from indications with existing over-the-counter commercial products (eg, topical antibiotics) to indications with few satisfactory over-the counter commercial products (eg, internal treatment of cancer, diabetes, hypertension, etc). In modern society, which is dominated by a bioscience paradigm, claims of efficacy need to be linked to specific chemical causes and mechanisms of action. Without these supporting scientific findings, M citrifolia,L fruit products would probably not have developed as rapidly as they have. It is interesting that although the rationale for turning to natural products is to avoid perceived harshness, reduction, and unnatural attributes of synthetic medicinal products, people still have a desire to know why a natural product works and expect that rationale to include a bioscience explanation of activity. This research may initially follow the implied indications of the culture that developed the plants use. Other leads may be followed as they arise from the research process. Although there do not seem to be traditional indications for its use in lifestyle disease , M.citrifolia is offering promise in this area.
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Degener O. In: Plants of Hawaii national park illustrative of plants and cus toms of the south seas . Photo-Lithoprint Reproductions, Braun-Brumfield, Inc. Ann Arbor, Michigan. 1973. Rock JF. In: The indigenous trees of the Hawaiian islands. Patronage. Honolulu, Hawaii. 1913. Stone BC. Morinda Linnaeus. Micronesica 1970; 6: 551-2. 69 Sturtevant EL. Sturtevants notes on edible plants (Hedrick U.P, editor). Albany, New York: JB Lyon Co; 1919. p 368. Terra JA. Tropical Vegetables. Ams terdam: Knoninklyk Ins tituut voor de Tropen; 1996. p 61. Turbott IG. Diets , Gilbert and Ellice Islands Colony. J Polynesian Soc 1949; 58: 36-46. Uhe G. In: Wayside plants of the south pacific. Stockton House R.D. 3. Albany, New Zealand. 1974.Wilder GP. In: The flora of Makatea. Bernice P. Bishop Museum Bulletin 120. Honolulu, Hawaii: Bishop Museum Press; 1934. Yuncker TG. In: The flora of Niue Island. Bernice P. Bishop Museum Bulletin, 178. Honolulu, Hawaii: Bishop Museum Press; 1943. Solomon N. Natures amazing healer, Noni. Pleas ant Grove, Utah: Woodland Publishing; 1998. Solomon N. The Noni phenomenon. Discover the powerful tropical healer that fights cancer, lowers high blood pres sure and relieves chronic pain. Direct Source Publishing; 1999. Solomon N. TAHITIAN NONI Juice: How much, how often, for what. Direct Source Publishing; 2000. Solomon N. TAHITIAN NONI JuiceThe pain fighter (arthritis/pain). Direct Source Publishing; 2001. Sharps J. NONI juice, A pres cription for the good health. Integrated Health Service; 2000. Veith I. Translated Yellow Emperors Classic of Internal Medicine (2500 BC); 2002. Du B, You S. Present situation in preventing and treating liver fibrosis with TCM drugs. J Tradit Chin Med 2001; 21:147-52. American Cancer Society: Statistics of cancer incidence. 2002. Lichtenstein P, Holm NV, Verkas alo PK, Iliadou A, Kaprio J, Koskenvuo M, et al. Environmental and heritable factors in the causation of cancer analys es of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000 343: 78-85.
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Perera P. Molecular epidemiology and prevention of cancer. Environ Health Perspect 1995; 103 (Suppl 8): 2336. American Ins titute for Cancer Research: 11th Annual Research Conference on Diet, Nutrition and Cancer. Washington DC. 2001. Rus so J , Russo IH. Experimentally induced mammary tumors in rats . Breast Cancer Res Treat 1996; 39: 7-20. elSisie AE, Hall P, Sim WL, Earnest DL., Sipes IG. Characterization of vitamin A potentiation of carbon tetrachlorideinduced liver injury. Toxicol Appl Pharmacol 1993; 119:280-8. Santella RM. DNA damage as an intermediate biomarker in intervention studies. Proc Soc Exp Biol Med 1997; 216: 166-71. Kens ler TW, Groopman JD. Carcinogen-DNA and protein adducts: biomarkers for cohort selection and modifiable endpoint in chemoprevention trials. J Cell Biochem Suppl 1996; 25: 85-91. Rabes HM. DNA adducts and cell cycle. J Cancer Res Clin Oncol 1986; 112: 18995. Hemminki K. DNA adducts , mutations and cancer. Carinogenesis 1993; 14: 200712. Poirier MC, Weston A. Human DNA adduct measurements: state of the art. Environ Health Perspect 1996; 104 Suppl 5:883-93. Slaga TJ. Multistage skin carcinogenesis: an useful model for the s tudy of the chemopreventionn of cancer. Acta Pharmacol Toxicol 1984; 55 Suppl 2: 107-24. Wang MY, Anderson G, Nowicki D. Preventive effect of Morinda citrifolia (Noni) at the initiation s tage of mammary breas t cancer induced by 7,12-dimethylbenz(a)anthracen (DMBA) in female Sprague-Dawley rats. The Proceedings of the Frontiers in cancer prevention research, AACR, Boston, 2002 Oct 17. Wang MY, Nowicki D, Anderson, G. Protective effect of Mor inda citr ifolia on hepatic injury induced by a liver carcinogen. The Proceedings of 93rd Annual Meeting of American Association for Cancer Research 2002; 43: 477. Wang MY, Su C, Nowicki D, Jensen J, Anderson G. Morinda citrifolia and cancer prevention. J Nutrition 2001; 131 (11S):3151S. Pryor WA. Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environ Health Perspect 1997; 105 Suppl 4: 875-82. Bartsch H, Nair J . New DNA-das ed biomarkers for oxidative stress and cancer chemoprevention studies. Eur J Cancer 2000; 36:1229-34.
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Wang MY, Lieher, JG. Induction by estrogens of lipid peroxidation and lipid peroxide derived malondialdehyde- DNA adducts in male Syrian hams ters : role of lipid peroxidation in estrogen-induced kidney carcinogenesis. Carcinogenesis1995; 16: 1941-5. Diplock AT, Charleux JL, Crozier-Willi G, Rice-Evans C, Roberfroid M, Stahi W, et al. Functional food science and defense against reactive oxidative species. Br J Nutr 1998; 80 Suppl 1: S77-112. Weisburger JH, Rivenson A, Garr K, Aliaga C. Tea, or tea and milk, inhibit mammary gland and colon carcinogenesis in rats . Cancer Lett 1997; 114: 323-7. Nishikimi M, Rao NA, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 1972;46: 849-54. Auerbach BJ , Kiely JS, Cornicell JA. A spectrophotometric microtiter-based assay for the detection of hydroperoxy derivatives of linoleic acid. Anal Biochem 1992; 201: 375-80. Wang MY, Su C. Cancer preventive effect of Mor inda citrifolia (Noni). Ann NY Acad Sci 2001; 952: 161-8. Wang MY, Su C. Cancer preventive effect of Morinda citrifolia. The proceedings of the Strang International Cancer Prevention Conference. 2000 Nov 10-11, New York. Wang MY, Su C, Nowicki D, Jensen J, Anderson G. Protective effect of Morinda citrifolia in carbontetrachloride-induced liver injury model: A light and electron microscopic s tudy. The Proceedings of the Eicosanoids and other Bioactive Lipids in Cancer, Inflammatory and Related Diseas es, the 7th Annual Conference, 2001 Oct 16. Loews Vanderbilt Plaza, Nashville, Tennessee, USA. Burns DM. Cigarette smoking among the elderly: disease consequences and the benefits of cess ation. Am J Health Promot 2000; 14: 357-61. Meerson FZ, Kagon VE, Kozolov YP, Belkina IM, Penko A. The role of lipid peroxidation in pathogenes is of ischemic damage and the antioxidant protection of the heart. Basic Res Cardiol 1982; 77: 465-85. Chow CK. Cigarette smoking and oxidative damage in the lung. Ann NY Acad Sci 1993; 686: 289-98. US Department of Health and Human Services. Reducing the health consequences of smoking 25 years of progress. A report of the Surgeon General. DHHHS Publ# (CDC) 1989; 89: 8411. Kozumbo WJ, Trush MA, Kens ler TW. Are free radicals involved in tumor promotion? Chem Biol Interact 1985; 54: 199-207.
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Hemminki K, Kumar R, Bykov VJ, louhelainen J, Vodicka P. Future research directions in the use of biomarkers. Environ Health Perspect 1996; 104 Suppl 3: 459-64. Wang MY, Dhingra K, Hittelman WN, Lieher JG, Andrade M, Li D. Lipid peroxdationinduced putative malondialdehyde- DNA adducts in human breast tissues. Cancer Epidemology, Biomarkers & Prevention 1996; 5: 705-10. World Cancer Res earch Fund and American Institute for Cancer Res earch: Food, nutrition, and the prevention of cancer: a global perspective. Published by the American Institute for Cancer Research, 1997. Fontham ET. Protective dietary factors and lung cancer. Int J Epidemiol 1990;19 Suppl 1:S32-42. Wang MY, Nowicki D, Anderson G, Su C, Jensen J. Protective effects of Morinda citrifolia on plasma superoxides (SAR) and lipid peroxides (LPO) in current smokers. The Proceedings of XIth Biennial Meeting of the Society for Free Radical Research International. July 16-20, 2002. Rene Des cartes University. Paris, France. in press. Natarajan K, Mori N, Artemov D, Bhujwalla ZM. Exposure of human breast cancer cells to the anti-inflammatory agent indomethacin alters choline phospholipid metabolites and Nm23 expression. Neoplasia 2002; 4:409-16. Yao M, Song DH, Rana B, Wolfe MM. COX-2 selective inhibition revers es the trophic properties of gas trin in colorectal cancer. Br J Cancer 2002; 87: 574-9. Takahashi T, Kozaki K, Yatabe Y, Achiwa H, HidaT. Increas ed expres sion of COX2 in the development of human lung cancer. J Environ Pathol Toxicol Oncol 2002; 21: 177- 81. Langman MJ, Cheng KK, Gilman EA, Lancashire RJ. Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research databas e. BMJ 2000; 320: 1642-6. Decensi A, Cos ta A. Recent advances in cancer chemoprevention, with emphasis on breast and colorectal cancer. Eur J Cancer 2000; 36: 694-709. Schreinemachers DM, Everson RB. Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology. 1994; 5: 138-46. Brigati C, Noonan DM, Albini A, Benelli R. Tumors and inflammatory infiltrates: friends or foes? Clin Exp Metastasis 2002; 19: 247-58. McMurray RW, Hardy KJ. COX-2 inhibitors: today and tomorrow. Am J Med Sci 2002; 323: 181-8. Dermond O, Ruegg C. Inhibition of tumor angiogenesis by non-steroidal antiinflammatory drugs : emerging mechanisms and therapeutic perspective. Drug Resist Updat 2001; 4: 314-21.
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Marrogi AJ, Travis WD, Welsh JA, Khan MA, Rahim H, Tazelaar H, et al. Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of no-small cell lung carcinoma. Clin Cancer Res 2000; 6: 4739-44. Colville-Nash PR, Gilroy DW, Potential adverse effects of cyclooxygenase-2 inhibition: evidence from animal models of inflammation. Biodrug 2001; 15: 1-9. Donnan GA, Davis SM. Aspirin therapy should be first line: probably, but watch this this space. Stroke 2002; 33: 2139-40. Komoike Y, Takeeda M, Tanaka A, Kato S, Takeuchi K.. Prevention by parenteral aspirin of indomethacin-induced gastric lesions in rats: mediation by salicylic acid. Dig Dis Sci 2002; 47: 1538-45. Koki AT, Masferrer JL. Celecoxib: a specific COX-2 inhibitor with anticancer properties. Cancer Control 2002; 9 (2 Suppl): 28-35. Horton JK, Williams AS, Smith-Phillips Z, Martin RC, OBeirne G. Intracellular measurement of prostaglandin E2: effect of anti-inflammatory drugs on cyclooxygenas e activity and prostanoid expression. Anal Biochem 1999; 271:18-28. Su C, Wang MY, Nowicki D, Jensen J, Anderson G. Selective COX-2 inhibition of Morinda citrifolia (Noni) in vitro. The proceedings of the Eicosanoids and other bioactive lipids in cancer, inflammation and related disease. The 7th Annual Conference, 2001 Oct 14-17. Loews Vanderbilt Plaza, Nashville, Tennessee, USA. Zhang LD, Zhang YL, Xu SH, Zhou G, Jin SB. Traditional Chinese medicine typing of affective disorders and treatment. Am J Chin Med 1994; 22: 321-7. Chang IM. Anti-aging and health-promoting constituents derived from traditional oriental herbal remedies: information retrieval using the TradiMed 2000 DB. Ann NY Acad Sci 2001; 928: 281-6. Chen J, Weng W. Medicinal food: the Chinese perspective. J Med Food 1998; 1: 117-22. Weng WJ, Chen JS. The eastern perspective on functional foods based on traditional Chinese medicine. Nutrition Rev 1996; 54: S11-6. Cheng TO. Hippocrates , cardiology, Confucius and the yellow emperor. Int J Cardiol 2001; 81: 219-33.
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G. Sathish Kumar
The effect of Noni (Morinda citrifolia L.) in Type 2 diabetes mellitus in inadequately controlled patients
Authors affiliation : G. Sathish Kumar Jehovah Raphahs Diabetic Centre, 41/B, Vasavi Nagar, Kharkhana, Secunderabad, Andhra Pradesh, India - 500 015.
Keywords : Diabetes mellitus, Noni food supplement
Abstract : The proper management of diabetes mellitus has assumed great importance in recent years in view of the steady increase in its prevalence all over the world including the USA and India. Apart from the suffering it causes to the individual in terms of morbidity, mortality, and decrease in quality of life, the economic costs of treating diabetes and the losses caused by decrease in productivity are a major source of worry to society and organizations concerned with public health. Both genetic and environmental factors are implicated in the causation of Type 2 diabetes. Among environmental factors; over eating decreased physical activity and obesity, cigarette smoking, increased oxidant stress, and inflammatory processes have been associated, either as a cause, or an effect of the developing diabetic state. Patients diagnosed with Type 2 diabetes milletus for at least 5 years, who are currently on insulin and not adequately controlled with current treatment, with HbA 1c> 8%. Present study highlights how patients inadequately controlled with an existing insulin treatment and Oral Hypoglasmic Agents (OHS). By adding Noni as a food supplement significant improvement in HbA 1c and FBG is observed after 6 months follow-up.
Correspondence to : G. Sathish Kumar Jehovah Raphahs Diabetic Centre, 41/B, Vasavi Nagar, Kharkhana, Secunderabad, Andhra Pradesh, India - 500 015.
Introduction
World Health Organization states that India and Asia Pacific regions continue to be at the forefront of diabetes mellitus epidemic, with consequences to health which threaten to be devastating. Younger members of our communities are not spared from the disease, with a significant problem emerging in the urbanized young in the most affluent parts of our country. Lifestyle changes and urbanization appear to be the underlying causes of this problem, the current number of people with diabetes in South East Asia is estimated to be 40 million, and this number will increase to at least 81.5 million by 2025. However, there is irrefutable evidence that diabetes can be prevented or delayed in people at high risk and that the progression of many of the complications associated with diabetes can be halted. Appropriate diet and physical activity,
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G. Sathish Kumar The effect of Noni (Morinda citrifolia L.) in Type 2 diabetes mellitus in inadequately controlled patients
maintaining a healthy body weight, refraining from tobacco smoking, and proper control of diabetes and blood pressure in people with diabetes will help prevent diabetes and reduce its complications. Each country needs to develop appropriate guidelines for the prevention and control of diabetes, and set up systems to ensure that these guidelines are adhered to. There is a need to establish the diagnostic criteria and classification, followed by target treatment of diabetes. The United Kingdom prospective diabetes study (UKPDS) showed that intensive treatment can decrease the morbidity and mortality of the disease by decreasing its chronic complications. However, the majority of patients with a longer duration of diabetes remain poorly controlled with oral agents, and the use of insulin, which could improve glyceamic control, is often long delayed and not aggressive enough. There is also limited information regarding next step therapy options for patients with diabetes who fail to achieve or maintain adequate glyceamic control with current treatment.
Materials and Methods

The study was done using randomized design with double blind (OHAs + Insulin/ OHAs + Noni) and Control - (only OHAs) for 24 weeks. A total of 305 patients attending the diabetic clinic for treatment were enrolled for this study. After a running in period of 3 months, the patients were randomized either to the control or to the study groups and followed up for next 6 months from April 2006 to September 2006. Drugs used : (i) Metformin, Glimiperide, Rosiglitazone and Insulin. (ii) Noni : Indian Noni 15ml twice a day on empty stomach given.
Results and Discussion

The results are presented in Table 1 & 2 and Figure 1 & 2. A perfect glyceamic control (fasting plasma glucose), HbA 1c increased insulin sensitivity improve C-peptide levels and improvement in fasting blood lipids, were observed (Heinicke 2001; Schecter S 1999)
21 Noni Cli. Res. J. 2007, 1(1-2)
Table. 1 Investigations and blood parameters. Outcome Contro (OHAS) OHAS + Insulin OHAS + Noni
Fasting Plasma Glucose (mg/dl) Baseline Week 4 Week 16 Week 24 223.2 248.4 248.4 237.6 223.2 201.6 183.6 172.8 230.4 190.8 165.6 111.6
HDL Cholestrol(mg/dl) Baseline Week 8 Week 16 Week 24 35.20 37.10 37.10 37.10 35.5 40.6 40.8 46.8 30.80 40.80 40.0 50.0
LDL Cholestrol(mg/dl) Baseline Week 8 Week 16 Week 24 125.2 125.2 125.2 120.0 121.6 118.8 116.0 112.0 125.4 120.4 109.0 97.0
OHAS : Oral Hypo Glyceamic Agents
Poor 0.90% Red
Good 34.30%
Green
Pink
Excellent 55.90%
Yellow Fair 8.70%

Fig. 1. Investigators over all Openion on Noni Treatment
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Table 2. Investigators over all opinion on Noni Treatment Opinion Excellent Good Fair Poor N (%) 55.90% 34.30% 08.70% 0.90%
50 45 40 35
30 25 20 15 10 5 0 OHA + Insulin Placebo OHA + Noni
Fig. 2 Percentage of Patients showed 1% or higher A1C reduction. OHAs and Noni are effective in achieving glycemic goal. Discussions : The study group showed a statistically significant better compliance than the control group on all parameters, Indian Noni, in patients with type 2 diabetes showed that, when used as a combination therapy (noni), this agents lowers fasting and postprandial glucose in patients with type 2 diabetes. The authors found Noni to be safe and well tolerated. Indian Noni proves definitely improves the quality living of the patients. Xeronine, the alkaloid of Noni in the presence of insulin activates the peripheral cell membrance insulin receptors and helps for the normal absorption of glucose. Low Glycemic index - A 3 : 1 ratio of carbohydrate to fibre in Noni juice helps to balance blood glucose levels. Noni modifies the body immune system to keep the sensitivity of beta cells intact and body develops resistance to many diseases. Noni helps in reducing anxiety, lessens the stress, response to some extent by elevating serotonin levels in blood.
23 Noni Cli. Res. J. 2007, 1(1-2)
In this research on diabetic practice, it was learnt that several micronutrients are normally deficient in patients with full blown diabetes. Noni, rich in antioxidants and micronutrients which are essential for all the diabetic patients. (Annonymous 1990) could meet the demand.
Conclusion
It can be said that Noni helps in type diabetes patients management.
References
Abbott., IA. 1985. The geographic origin of the plants most commonly used for medicine by Hawaiians. J. Ethnopharmacol 14 : 213-22. Annonymous., 1990. WHO Study Group Diet, Nutrition and Prevention of Chronic Diseases, Geneva : World Health Organisation. Heinicke., R. 2001. The Xeronine system a new cellular mechanism that explains the health promoting action of Noni and Bromelian. Direct Source Publishing; USA. Leeds., M.J. 1958. Nutrition for Healthy Living, Boston : WCB McGraw Hill Pub, 1998. Schecter., S. 1999. Nonu-Natures True Adaptogen from the South Pacific, Total Health, Vol 21.2 Shaprs., J. 2000. Noni Juice, A prescription for the good health. Integrated Health Service, 2000. Solomon., N. 1999. The tropical fruit with 101 medicinal uses, Noni Juice. 2nd ed. Woodland Publishing US 1999.
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Periyasamy Selvam Narayanan Murugesh Myriam Witvrouw
Studies of Comparative Anti-HIV Activity and cytotoxicity of Morinda citrifolia L.
Authors affiliation : Periyasamy Selvam Narayanan Murugesh Myriam Witvrouw Arulmigu Kalasalingam College of Pharmacy, Krishnankoil, 626 190, India Institute of Pharmacology, Madurai Medical College, Madurai-625 020, India Molecular Medicine, Katholieke Universiteit-Leuven and IRC KULAK, Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium. Correspondence to : Periyasamy Selvam Arulmigu Kalasalingam College of Pharmacy, Krishnankoil, 626 190, India Email : periyasamyselvam2001@yahoo.co.in
Keywords : Anti-HIV Activity, cytotoxicity and Morinda citrifolia
Abstract : Fruit juice and ethanol, methanolic extract of fruit powder of Morinda citrifolia (MC) have been studied against the replication of HIV-1(III B) in MT-4 cells. Fruit juice of Morinda citrifolia (MC) exhibited a maximum protection of 18% of the cells against the cytopathic effect of HIV-1(IIIB) strain and displayed marked cytotoxic activity in lymphocyte (MT-4) cells (CC50: 0.19 mg/ml). However the ethanol (EMC) and methanol extracts (MMC) displayed cytotoxic activity (CC50) in lymphocyte (MT-4) cells only at higher concentration the CC50 being at 72.34 and 220 g/ml, respectively.
Introduction
Acquired immuno deficiency syndrome (AIDS) is a life threatening and debilitating disease state caused by retrovirus infection, and the etiologic agent is now widely known as the human immunodeficiency virus type 1. Many compounds of plant origin have been identified that inhibit different stages in the replication cycle of HIV (Wu., et al 2004; Sanchez et al., 2001; Shahidul et al., 2000, Hu et al., 2000). Morinda citrifolia L (Noni) has been used in folk remedies by Polynesians for over 2000 years, and is reported to have a broad range of therapeutic effects, including antibacterial, antiviral, antifungal, antitumor, antihelminth, analgesic, hypotensive, anti-inflammatory, and immune enhancing effects(Wang MY et al 2002). The present study is designed to determine the antiviral activity of fruit juice and ethanolic (EMC) and methanolic (MMC) extract of Morinda citrifolia (MC) against the replication of HIV-1(IIIB) in MT-4 cells and Cytotoxicity in mockinfected MT-4 cells was also assessed by the MTT method.
Material and Methods

Extraction : Fruit juice of Morinda citrifolia is a gift from Health India Laboratory, Chennai, Tamilnadu, India, and the fruit powder of Morinda citrifolia was subjected to hot continuous percolation using methanol and ethanol. The methanol (MMC) and ethanol (EMC) extract of Morinda citrifolia were concentrated by distillation and used for screening.
25 Noni Cli. Res. J. 2007, 1(1-2)
Periyasamy Selvam et al. Studies of Comparative Anti-HIV Activity and cytotoxicity of Morinda citrifolia L.
Anti-HIV Assay. Morinda citrifolia was tested for its inhibitory effects against the replication of HIV-1(IIIB) in MT-4 cells (Pauwels et al, 1988; Witvrouw et al, 2004). The MT-4 cells were grown and maintained in RPMI 1640 DM Medium supplemented with 10% (v/v) heat-inactivated Fetal Calf Serum (FCS), 2 mMglutamine, 0.1% Sodium bicarbonate and 20mg/ml gentamicin (culture medium). Inhibitory effect of MC on HIV-1 replication was monitored by inhibition of virusinduced cytopathic effect in MT-4 cells and were estimated by MTT assay. Briefly, 50 ml of HIV-1 and HIV-2 (100-300 CCID 50) were added to a flat-bottomed microtiter tray with 50 ml of medium containing various concentrations of extracts of MCT. MT-4 cells were added at a final concentration of 6x105 cells/ml. After 5 days of incubation at 37C, the number of viable cells were determined by the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Cytotoxicity of MC against mock-infected MT-4 cells was also assessed by the MTT method.

The anti-HIV data are presented in Table 1. Table1. Anti-HIV (III B) Activity and Cytotoxicity of Morinda citrifolia in MT-4 cells Compound MC EMC MMC AZT (STD)
a
EC50a (g/ml) >0.19 >72.34 >220 0.0062
CC50b (g/ml) 0.19 72.34 220 65.65
Maximum % Protection 18 0 0 106
Concentration required to inhibit the cytopathic effect of HIV-1(IIIB) in MT-4 cells by 50%.
b
Concentration required to cause cytotoxicity to 50% of the MT-4 cells.
An ethanolic, methnolic extract and fruit juice of Morinda citrifolia has been evaluated for its anti-HIV activity and cytotoxicity (Table 1) against HIV-1(III B) replication in acutely infected MT-4 cells. Morinda citrifolia exhibited a maximum protection of 18% of the MT-4 cells against the cytopathic effect of HIV-1(IIIB) after acute infection. Morinda citrifolia displayed marked cytotoxic activity in lymphocyte (MT-4) cells (CC50: 0.19 mg/ml). Both ethanol (EMC) and methanol extracts (MMC) displayed cytotoxic activity (CC50) in lymphocyte (MT-4) cells at 72.34 and 220 g/ml respectively.
Noni Cli. Res. J. 2007, 1(1-2) 26
Periyasamy Selvam et al. Studies of Comparative Anti-HIV Activity and cytotoxicity of Morinda citrifolia L.
Acknowledgement
We acknowledge A. Nijs and B. Van Remoortel for excellent technical assistance. We thank the NIH AIDS Research and Reference Reagent Programme, Division of AIDS, NIAID for providing the HIV-1(IIIB) strain and MT-4 cells. Work at KULeuven is supported by the European Commission (CSHB-CT-2005-505480).World Noni Research foundation for financial support. Author is grateful to Dept of Science and Technology for award of BOYSCAST fellowship for this research work.
References
Hans R. 1994. Studies on the anti-leukemia activity of Indigofera tinctoria. Stem cell, 12: 53-63. Hu K, Kobayashi H, Dong A, Iwasaki S, Yao X. 2000. Antifungal, antimitotic and anti-HIV-1 agents from the roots of Wikstroemia indica. Planta Med. 66:564-7. Muruganandhan AV, Battacharya SK, Ghosal S. 2000. Indole and flavanoid constituents of Wrightia tinctoria. Indian J Chem, 39B, 125-131. Pauwels R, Balzarini J. Baba M, Snoeck R, Schols D, Herdewijn P, Desmyter J, De Clercq E. 988. Rapid and automated tetrazolium-based colorimeteric assay for detection of antiHIV compounds J. Virol. Methods. 20: 309-321. Sanchez Palomino S, Abad MJ, Bedoya LM, Garcia J, Gonzales E, Chiriboga X, Bermejo P, Alcami J. 2001. Isolation of an anti-HIV diprenylated bibenzyl from Glycyrrhiza lepidota Phytochemistry. 58:153-7. Shahidul Alam M, Quader MA, Rashid MA. 2000. HIV-inhibitory diterpenoid from Anisomeles indica. Fitoterapia, 71:574-6. Witvrouw M, Pannecouque C, Switzer W, Folks T, De Clercq E, Heneine W. 2004. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV compounds: implications for treatment and postexposure prophylaxis. Antiviral Therapy, 9: 57-65. Wu PL, Lin FW, Wu TS, Kuoh CS, Lee KH, Lee SJ. 2004. Cytotoxic and anti-HIV principles from the rhizomes of Begonia nantoensis. Chem Pharm Bull, 52:345-9. Wang MY, West BJ, Jensen CJ, Nowicki D, Su C, Palu AK, Anderson G. 2002 Morinda citrifolia (Noni): a literature review and recent advances in Noni research. Acta Pharmacol Sin. 2002 Dec;23(12):1127-41.
27 Noni Cli. Res. J. 2007, 1(1-2)
Effects of Noni (Morinda citrifolia L.) on Carcinoma of Breast
Authors affiliation : Dr. Rangadhar Satapathy MIG II, 6/2, BDA colony, Chandrasekharpur, Bhubaneswar, Orissa, India
Keywords : Carcinoma, Morinda citrifolia anticarcinogenic agents.
Abstract : Breast cancer is the fifth most common cause of cancer death (after lung cancer, stomach cancer, liver cancer, and colon cancer). In 2005, breast cancer caused 502,000 deaths (7% of cancer deaths; almost 1% of all deaths) worldwide. Among women, breast cancer is the most common cause of cancer death. The mainstay of breast cancer treatment is surgery when the tumor is localized, with possible adjuvant chemotherapy, and/or radiotherapy. Depending on clinical criteria (age, type of cancer, size, metastasis) patients are roughly divided in to high risk and low risk cases, with each risk category following different rules for therapy. Treatment possibilities include radiation therapy, chemotherapy, hormone therapy, and immune therapy. Nothing guarantees that you wont develop breast cancer. There are lots of side effects of chemotherapy and radiotherapy that makes the patient worse than cancer itself. Indian Noni helps to overcome maximum side effects of all cancer cases including the breast cancer by its immune enhancing and nutritive supplementing property. It also contains many bio anti carcinogenic ingredients that helps by enhancing the efficacy of the cancer treatment too. It acts as a tool for primary prevention, secondary prevention and as an adjuvant immune enhancing supplement with the common line of cancer treatment.
Correspondence to : Dr. Rangadhar Satapathy MIG II, 6/2, BDA colony, Chandrasekharpur, Bhubaneswar, Orissa, India
Introduction
Breast cancer, the second-leading cause of cancer deaths in India, is the disease women fear most. Breast cancer can also occur in men. Today, radical mastectomy is rarely performed. Most breast lumps arent cancerous. Yet the most common sign of breast cancer for both men and women is a lump or thickening in the breast. Often, the lump is painless. In breast cancer, some of the cells in the breast begin growing abnormally. These cells divide more rapidly than healthy cells do and may spread (metastasize) through the breast, to the lymph nodes or to other parts of the body. The most common type of breast cancer begins in the milk-producing ducts, but cancer may also begin in the lobules or in other breast tissue. In most cases, it isnt clear what causes
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Dr. Rangadhar Satapathy Effects of Noni (Morinda citrifolia) on Carcinoma of Breast
normal breast cells to become cancerous. Doctors do know that only 5 percent to 10 percent of breast cancers are inherited. Treatments exist for every type and stage of breast cancer. Most women will have surgery and an additional (adjuvant) therapy such as radiation, chemotherapy or hormone therapy. Because breast cancer treatment is likely to damage healthy cells and tissues, unwanted side effects are common. Specific breast cancer side effects depend mainly on the type and extent of the treatment. Side effects of breast cancer radiation therapy including uncommon side effects that may involve the heart, lungs, and ribs. One of the common side effects of breast cancer radiation treatment is fatigue, especially in the later weeks of treatment and for sometime afterward. The side effects of chemotherapy depend mainly on the drugs the patient receives. As with other types of breast cancer treatment, side effects vary from person to person. In general, anticancer drugs affect rapidly dividing cells. These include blood cells, which fight infection, cause the blood to clot, and carry oxygen to all parts of the body. When blood cells are affected by anticancer drugs, patients are more likely to get infections, bruise or bleed easily, and may have less energy during treatment and for some time afterward. Cells in hair follicles and cells that line the digestive tract also divide rapidly. As a result of chemotherapy, patients may lose their hair and may have other side effects, such as loss of appetite, nausea, vomiting, diarrhea, or mouth sores.
Indian Noni and Cancer

Noni ppt (The polysaccharide) Noni has anti tumor activity by stimulating immune factors like TNF, NK cells etc. to attack the tumor. Noni ppt (The polysaccharide) is one unique polysaccharide that can be used as a chemo-immunotherapy agent to treat cancer. NONI-ppt present in NONI develops an anti-tumor response by stimulating the release of various cytokines mediator of the immune system of our body like Interleukin Interferon gamma Nitric oxide Tumour necrosis factor Natural killer cells Thus they help in controlling carcinogenesis by inhibiting the growth and mutation of the malignant cells
29 Noni Cli. Res. J. 2007, 1(1-2)
Pretreatment with Noni followed by ultraviolet irradiation increased the levels of phosphorylated extra cellular signal-regulated kinases (ERK) and stressactivated protein kinases (SAPK) enzymes in the body. Activation of SARK and ERKs plays an important role in triggering apoptosis. Thus their activation proves the stimulatory effect of Noni on ultraviolet-induced apoptosis. Thus Noni can be used as an immune supplemental therapeutic agent with any cancer therapy. Noni exhibits antiangiogenesis effects on the malignant cells. The cancer tumor has the ability to develop its own blood vessels around it to get their nutrition for growth by the process of angiogenesis. About 150+ phytochemicals present in Noni like Damnacanthal, Alcerin, limonene, Epigallocatechin gallate (EGCg) etc, to name a few, exhibit antiangiogenesis effect on the malignant cells thus inhibiting the growth and mutations of these cells and induces program cell death or apoptosis.. Epigallocatechin gallate (EGCg)- EGCg is a polyphenolic flavonoid antioxidant that is found in abundance in Noni. EGCg in Noni inhibits the quinol oxidase (NOX) enzyme including tumor activity, thus helping in antiangiogenesis. NOX enzymes are found in a variety of cell types and tissues where they react with oxygen to generate reactive oxygen species (ROS), the free radical forms of oxygen that damage the DNA of cell. The ROS is involved in mutations and tissue damage in diseases such as cancer and rheumatoid arthritis. Normal amounts of NOX production are important to regulate the cell growth. It is generally inactive during the normal cell division process, in response to growth hormone stimulation but it is active in cancerous cells and responsible for the cancerous cell proliferation, cell motility, invasion and angiogenesis process, all of which are prerequisites for tumor metastasis. EGCg, a primary component of Noni inhibits the NOX activity of cancer cells. According to Dr. Morres experimental studies it is found that EGCg in Noni inhibits NOX carcinogenesis activity but does not inhibit the NOX activity of healthy cells. Noni prevents the carcinogen DNA adduct formation on cell Noni Prevents DNA adduct formation, and hence protects the cell from converting to cancer. Hence Noni can be used for primary and secondary prevention of cancer. Most chemical carcinogens binds to our genetic DNA to form DNA adducts. Carcinogen DNA adducts formation causes DNA damage. Carcinogen DNA
Noni Cli. Res. J. 2007, 1(1-2) 30
adducts can be repaired by body enzymes. The unprepared DNA damaged cell will be responsible for mutation and consequent cancer development. Therefore preventing carcinogen-DNA adduct formation is a key step for primary prevention in cancer at the initiation of carcinogenesis. Noni helps to check the carcinogen DNA adduct formation. Hence it may prevent cancer at the initiation stage of carcinogenesis.
Role of Antioxidant in Cancer Prevention

Oxidative stress in our body is the underlying cause of cancer. When excessive free radicals are allowed to exist near the nucleus of cell, significant damage to the DNA of cell can result. Free radicals can also wreck damage on the genetic structure of the DNA, which can then lead to abnormal growth of cell. As these cells continue to replicate, this mutated DNA is carried to each newly developed cell. When there is further oxidative stress to this mutated DNA of the cell, more damage occurs. The cell will then begin to grow out of control. It spreads from one part of the body to other(metastasis), thus becoming a true cancer. Oxidative stress is indeed the cause of cancer and antioxidants used to bring free radical back into balance would lower the risk of cancer. Therefore the bet strategy is to maximize your own bodys immune system and antioxidant defense and this begins by eating a healthy natural suppliment that rich with antioxidants. Noni is the rich source of antioxidants. The high anti oxidant property of Noni helps to prevent the formation of carcinogen-DNA adducts. It was hypothesized that the antioxidants in Noni may have cancer protective effects by scavenging reactive oxygen free radicals and quenching lipid peroxides. In vitro study shows that the Damnacanthal, one phytochemical present in Noni have anti-carcinogenic effect. Glutathione S-transferase (GST) The Glutathione S-transferase (GST) is a system which eliminates carcinogens. Limonene, present in Noni juice seems to promote the GST system in the liver and small bowel, thereby decreasing the damaging effects of carcinogens. Animal studies demonstrated that dietary limonene present in Noni reduced mammary tumor growth. Noni inhibits Matrix metalloproteinases (MMPs) enzyme Matrix metalloproteinases (MMPs), the enzyme have been identified as key players in tumor invasion and metastasis. Excessive MMPs secretion has been regarded as an index of malignancy which leads to the degradation of extra
31 Noni Cli. Res. J. 2007, 1(1-2)
cellular matrix. Lysine and proline are building blocks of collagen fibers that stabilize connective tissue by inhibiting the enzymatic digestion of collagen fibers. Vitamin C is essential for production of collagen and acts as a powerful antioxidant by scavenging free radicals and thereby protects cells from damage. Epigallocatechin gallate (EGCG) has antioxidant and anticancerogenic properties. It prevent cancer cell invasion by inhibiting MMPs. The natural amino acid lysine, especially in combination with vitamin C and other selected cellular nutrients, is capable of blocking this collagen digestion. Noni contains the above two amino acids lysine and proline. Noni is rich with vitamin C. Noni contain the phytochemical Epigallocatehin gallate (EGCG). Hence Noni should help to prevent the cancer tumor invasion and metastasis. Limonene, the phytochemical present in Noni increases the levels of liver enzymes involved in detoxifying carcinogens. Many recent studies have shown that elevation of phase II enzymes, such as NAD(P) H : quinone reductase (QR) and GST, correlates with protection against chemical - induced carcinogenesis in animal models, in the stage of promotion as well as initiation. Noni fruits contain an extremely potent quinone reductase inducer, 2 - methoxy - 1,b,6 - trihydroxyanthraquinone. This new anthraquinone was nearly 40 times more potent than any other quinone. Noni contain many glycosides Noni contains many glycosides. Asperuloside is a glycoside. Traditionally, this glycoside has been used for diurises. Research has indicated that it is also an anticlastogenic (that is, prevents the breakage of chromosomes). As a result, it is anti-mutagenic or resists mutation within the cells DNA. Three new glycosides as listed below were isolated from Morinda citrifolia (Noni) fruit are : 1. 6-O- (beta-D-glucopyranosy) -1-O-octanoyl-beta-D-glucopyranose, 2. 2. 6-O- (beta-D-glucopyranosy) -1-O-hexanoyl-beta-D-glucopyranose, 3. 3-methylbut-3-enyl6-O-beta-D-glucopyranosyl-beta-D-glucopyranoside.
Noni clinical trail

The patient named Mrs. Lalita pahan from Berhampur, orissa is suffering from carcinoma of breast. Her condition was pretty worse before 4 months. The whole right breast and axillary portion had severe swelling with radiating pain from breast to axial and back. There was a big nodular hard mass inside the right breast. Her treating physician sent her for the FNAC report of that portion and it was detected cancer of breast. She was advised for the operation as the cancer had already spread to the axillary lymph nodes. Due to financial problem
Noni Cli. Res. J. 2007, 1(1-2) 32
she did not go for operation. Then she started consuming Noni. After taking Noni for three months her hard nodular mass softened and gradually reduced in size. The surrounding swellings of the mammary gland gradually improved. The pain reduced a lot and occasional bleeding was observed for a month. Now the condition has improved more than 70 % than before. She is now continuing Noni internally as well as applying Noni externally.
Conclusion
Current treatment protocols with chemotherapy and / or radiation although beneficial, is toxic and has the potential to destroy healthy cells as well. Our approach has been to develop strategies to inhibit cancer development, progression and metastasis using naturally occurring nutrients, which are relatively non-toxic. Indian Noni is one among them. It contains the entire major and most of the micro nutrients. Noni is helpful for cancer patient. Along with all the cancer treatment if Noni is added with their treatment protocol it will cover maximum side effects of chemotherapy or radio therapy; acts as an immune supplemental adjuvant to the current therapy; as it prevents the DNA adduct formation it help in primary prevention and secondary prevention for all cancer patient or those with family history of cancer treatment.
References
Su BN, Pawlus AD, Jung HA, Keller WJ, McLaughlin JL, Kinghorn AD. Potent antioxidants found in Noni. Source: Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA. Wang MY B.J. West; C.J. Nowicki, D.; C.Su; A.K. Palu.; and G. Anderson 2002 Acta Pharmacol Sin Dec; 23 (12): 1127-1141. Morinda citrifolia (Noni): A literature review and recent advances in Noni research. WANG Mian-Ying, Brett J WEST, C Jarakae JENSEN, Diane NOWICKI, SU Chen, Afa K PALU, Gary ANDERSON. University of Illinois College of Medicine, Department of Pathology, 1601 Parkview Avenue, Rockford, IL 61107, USA; Department of R & D, Morinda Inc, Provo, Utah 84606, USA.
33 Noni Cli. Res. J. 2007, 1(1-2)
Effect of Noni on Filarial Worm Infestation In Vitro Study
Authors affiliation : Dr. Rangadhar Satapathy MIG II, 6/2, BDA colony, Chandrasekharpur, Bhubaneswar, Orissa, India
Keywords : Noni higher concentration and filarial worm.
Abstract : Lymphatic Filariasis is a parasitic and infectious tropical disease, caused by the thread-like parasitic filarial worms, Wuchereria bancrofti, Brugia malayi, and Brugia timori, all transmitted by mosquitoes. The most spectacular symptom of lymphatic filariasis is elephantiasis (thickening of the skin and underlying tissues), which was the first disease discovered to be transmitted by insects. Elephantiasis is caused when the parasites lodge in the lymphatic system. Elephantiasis affects mainly the lower extremities, whereas ears, mucus membranes, and amputation stumps are rarely affected; however, it depends on the species of filaria. W. bancrofti can affect the legs, arms, vulva, breasts, while Brugia timori rarely affects the genitals. One vitro study showed that the adult parasite of Wuchereria bancrofti died within 20 hours in the culture media mixed with Noni in comparison to the control group which survived for 60 hours without adding Noni. Similarly extract of Noni induces paralysis and death of parasitic nematode worm of the human Ascaris Lumbricoides, within a day. A botanist via Morton, botanist reported that Noni has been used in the Philippines and Hawaii as an effective insecticide. Hence it can be suggested to prescribe Noni along with other medication of the filariasis.
Correspondence to : Dr. Rangadhar Satapathy MIG II, 6/2, BDA colony, Chandrasekharpur, Bhubaneswar, Orissa, India
Introduction
It has been shown that Noni has anti helminthic effect on Round worm (Ascaris umbricoids). Noni has been used in the Philippines and Hawaii as an effective anti-parasitic. On that basis an invitro study of the effects of Noni juice on both adult and microfilaria of cattle parasite Setaria digitata has been conducted. Lymphatic Filariasis is a parasitic and infectious tropical disease, caused by three thread-like parasitic filarial worms, Wuchereria bancrofti, Brugia malayi, and Brugia timori, all transmitted by mosquitoes The signs and symptoms: lymph adenoma, massive leg swelling, elephantiasis, lymphangitis, fever, pain epididymitis, orchitis, eosinophilia, etc.
Noni Cli. Res. J. 2007, 1(1-2) 34
Dr. Rangadhar Satapathy Effect of Noni on Filarial Worm Infestation In Vitro Study
With the objective to evaluate the effect of Noni on different stages of filarial parasites a study was carried out and the details with results are furnished in this paper.
Materials and Method

1. Collection of Setaria digitata: Adult female setaria digitata, cattle filarial parasites were collected from the local slaughter house. 2. Collection of Microfilaria: Adult parasites were cut into different pieces in the ISCOV medium and kept at 37 C for an hour. Microfilaria were harvested after centrifuging at 10000 RPM Microfilaria count was then adjusted to 2000 mf / ml of medium. 100 micron medium = 200 mf +Noni Medium : Adult Setaria digitata parasites were incubated at 37C in ISCOV medium at antibiotic and antimycotic care with 10% FCS (Foetal calf serum) at 5% CO2.
Different Noni dilutions

Two dilutions of Noni were prepared 1. N: 50 (i.e. one part Noni with 50 parts of medium) 2. N: 25 (i.e. one part Noni with 25 part medium). Both the Noni dilutions were filtered through 25 micron filter before adding to the culture medium. Control group of parasites were cultured in the medium without Noni that is named C 1. Effects of Noni on adult parasite was studied an in vitro in 3 groups of medium. Medium and groups 1. 2. 3. 4. Control group C ( no dilution of Noni) Group 1 (where N: 50 Noni dilutions were added with the culture medium). Group 2 (where N: 25 Noni dilutions were added with the culture medium. Adult parasites were taken in each group
Observation The motility of the adult parasites was noted at day 1, 2, and 3. It was found that At day1 the motility was almost same in each group At day 2 (after 24 hrs) the motility of Gr-1 and Gr-2 were sluggish than control.
35 Noni Cli. Res. J. 2007, 1(1-2)
Dr. Rangadhar Satapathy Effect of Noni on Filarial Worm Infestation In Vitro Study
At day 3 (after 48 hrs) some parasite of Gr-1 and Gr-2 were dead and the rest of them were moving very slowly
Effects of Noni on Microfilaria - An In Vitro Study

Medium and group - Same ISCOV medium Same 3 groups were prepared 1. Control group C ( no dilution of Noni) 2. Group 1 (where N: 50 Noni dilutions were added with the culture medium). 3. Group 2 (where N: 25 Noni dilutions were added with the culture medium. About 200 microfilaria were taken in each group. Observations The motility of the microfilaria was noted at day 1, 2, 3 & 4. It was found that : At day one the motility was almost same in each group At day two (after 24 hrs) the motility of Gr-1 and Gr-2 were sluggish than control. Gr-2 motility was more sluggish than Gr-1 At day three (after 48 hrs) the motility of Gr-1 was remarkably sluggish and Gr-2 were found dead without any movement. At day four (after 72 hrs) the microfilaria in both the Gr-1 and Gr-2 were found dead without any movement
Conclusion
This study brought out the fact that Noni induces neuromuscular effects (paralysis) and death of the filarial parasite both in adult and microfilaria at higher concentrations within 48 hours.
Noni Cli. Res. J. 2007, 1(1-2) 36
N. Murugesh A.J.M. Christina N. Chidambaranathan
Anti-fibrotic effect of Noni (Morinda citrifolia. L) on carbon tetrachloride induced liver fibrosis
Authors affiliation : N. Murugesh A.J.M. Christina N. Chidambaranathan Institute for Pharmacology, Madurai Medical College, Madurai, Tamil Nadu, India. Department of Pharmacology, K.M. College of Pharmacy, Uthangudi, Madurai, Tamil Nadu, India - 625107. Department of Pharmacology, K.M. College of Pharmacy, Uthangudi, Madurai, Tamil Nadu, India - 625 107.
Keywords : Morinda citrifolia L. , Antifibrolic effect liver
Abstract : A study was carried out to investigate the effect of Noni against carbon tetrachloride (CCl4), induced liver fibrosis. Liver fibrosis was induced by twice/week administration of CCl4 at a dose of 1 ml/ kg weight mixed with an equal volume of corn oil. The extent of liver fibrosis was assessed by the content of hydroxyproline in liver, serum level of asparate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin. Treatment with Noni reduced the hydroxyproline content of liver, serum enzyme levels and total bilirubin. These observations confirm the antifibrotic effect of extract.
Correspondence to : N. Murugesh Institute for Pharmacology, Madurai Medical College, Madurai, Tamil Nadu, India.
Introduction
Fibrosis is seen as a scar formation in liver (Borchers et. al., 2000). Hepatic fibrosis is the result of chronic viral, toxic auto immune or cholestatic liver injury (Wasmuth, et. al., 2003). Viral infection seems to be a crucial factor in liver fibrosis. Numerous chemicals and drugs can harm the liver (Chojkier and Brenner, 2003). In many experimental fibrotic models, CCl4 was used to induce hepatic injury (Madro, et. al., 2002). Some workers have used N-nitro dimethyl amine (NMDA) to injure rat liver and have reported that hyaluronic acid plays a role in the pathogenesis of liver fibrosis (George, et. al., 2004). Likewise, bile duct ligation technique was used by many workers to induce fibrosis (Kountouras, J., et. al., 1984; Turkacaper, N., et. al., 2003). In this study CCl 4 induced liver fibrosis was used as a model to evaluate the antifibrotic effect of Noni.
Materials and Methods Animals

Male albino Wistar rats (150 200 g) were purchased from Chellamuthu Trust, 0 Madurai. They were housed in groups of 3 to 4/cage, maintained at 25 + 2 C under 12 hour light -dark cycle. They were fed with standard pellet diet and water ad libitum.
37 Noni Cli. Res. J. 2007, 1(1-2)
N. Murugesh et al. Anti-fibrotic effect of Noni (Morinda citrifolia. L) on carbon tetrachloride induced liver fibrosis
Induction of liver fibrosis by Carbon Tetrachloride

CCl4 was given to rats orally twice a week for 28 days at the dose of 1 ml/kg body weight mixed with an equal volume of corn oil (Bickel, et. al., 1991). Three days after the last dose, rats were sacrificed under light anesthesia and blood and liver samples were collected for biochemical studies.
Treatment with Noni

The diluted Noni extract was given orally by gavage for 28 days at a dose of 5 ml. The control group received equal amount of distilled water, given orally for 28 days. For comparison a group of normal rats was used throughout. The body weight of the animals was recorded every day for this study.
Estimation of serum biochemical parameters

After 28 days, the rats were sacrificed under light anesthesia and blood was collected by cardiac puncture. A part of it was used for biochemical estimation and centrifuged at 3000 rpm to obtain serum. The levels of asparate transaminase (AST), alananine transaminase (ALT), alkaline phosphatase (ALP) and total billirubin were estimated by standard procedures.
Determination of Hydroxyproline content in liver

The hydroxyproline content of liver was determined by the method suggested by Jamall, et. al., (1981). The specimens of liver were weighed and hydrolysed completely in 6 M HCl. A fraction of the sample was derivatised using Chloramine T solution and Erhlichs reagent. The density was measured at 558 nm.
Statistical analysis
The values are expressed as mean +SEM. The data were analysed using one way ANOVA followed by Newman Keuls multiple range tests. Differences below P < 0.05 implied significance.
Results
The results are presented in Tables 1 and 2. Table 1: Effect of Noni on the biochemical parameters of rats treated with CCl 4 Treatments Normal rats CCL4 treated rats CCL4 + Noni treated rats AST IU/L 159 +6 289 +1.1* 175+ 8* a ALT/IU/L 47+ 2.2 102 +5* 61+4* a ALP IU/L 215 + 6.8 396+8* 235 +13.2* a Total Bilirubin mg/dl 0.48 + 0.01 1.6 + 0.08* 0.7 +0.03*a
Noni Cli. Res. J. 2007, 1(1-2) 38
Data are mean + SEM. n=6, Newman Keuls multiple test was used (P<0.05). * Significantly different from normal rats. * a significantly different from CCl4 treated rats. Table 2: Hydroxyproline content of liver and liver weight following various treatments Treatment Normal rats CCL4 treated rats CCL4 + Noni treated rats Hydroxyproline Content (mg/g liver) 53 + 3 124 +7 77 + 3 *a Liver weight on day 28 3.5 + 0.02 4.5 + 0.06 3.8 + 0.07 *a
Data are mean + SEM. n = 6, Newman Keuls multiple test was used (P<0.05) * significantly different from normal rats. *a significantly different from CCl4 treated rats.
Serum parameters
Treatment with CCl 4 altered various tissue and serum parameters and also the architecture of liver. In CCl4 treated rats, the serum parameters AST, ALT, and ALP were significantly elevated. The bilirubin level was also high. However, in CCl4 + Noni treated rats, the serum levels of these enzymes and bilirubin were significantly low when compared to CCl4 alone treated rats.
Tissue parameters
The main tissue parameters assessed were hydroxyproline content and weight of liver. Hydroxyproline was elevated following CCl4 treatment. Treatment with the extract reduced this parameter. Liver weight was increased in CCl4 treated rats which was reduced by Noni.
Discussion
Large literature states that collagen content in the extracellular matrix is high in fibrosis, the extent of which could be assessed by the hydroxyproline content (Muriel and Escobar, 2003). Many earlier studies have reported high hydroxyproline content in association with liver fibrosis. Present study showed a high hydroxyproline content in CCl4 treated rats, indicating the development of fibrosis, which was brought down by co-treatment with Noni. In the present study, CCl 4 the toxicant that injures liver is converted to trichloromethyl radical by the enzyme cytochrome P450 which initiates lipid
39 Noni Cli. Res. J. 2007, 1(1-2)
peroxidation and liver damage. Hence, liver damage was reflected by high levels of serum AST, ALT, ALP and bilirubin in CCl 4 treated rats. The rats treated with CCl4 + Noni showed low levels of AST, ALT, ALP and bilirubin. These observations suggest that Noni is effective against CCl4 induced liver fibrosis in rats.
Conclusion
This study has indicated the protective effect of Noni against CCl4 induced chronic liver injury. This conclusion was based on the correction of serum as well as tissue parameters by Noni.
References
Bickel, M. Baader, E. and Brocks, D.G. 1991. Beneficial effect of inhibitors of prolyl 4-hydroxylase in CCl4 induced fibrosis of liver in rats. J. Hepatol. 13, 2633. Borchers, A.J. Sakai, S. and Henderson, G.L.2000. Learning about liver fibrosis. Gut 46, 443-446. Chojkier, M. and Brenner, D.A. 2003. Chemical and drug induced liver injury. Am. J. Pathol. 163, 1653 1662. George, J. Tsutsumi, M. and Takase, S. 2004. Expression of hyaluronic acid in Nnitroso dimethylamine induced hepatic fibrosis in rats. Int. J. Bio chem. Cell boil. 36, 307-319. Jamall, I.S. Fenelli, V.N. and Que Hee, S.S. 1981 . A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues . Anal. Biochem. 112, 70-75. Kountouras, J. Billing, B.H. and Seheuer, P.J. 1984 . Prolonged bile duct obstruction. A new experimental model for cirrhosis in rats. Br.J. Exp. 65, 305 311. Madro, A. Slomka, M. and Celenski, K. 2002. The influence of interferon alpha on rat liver injured by chronic administration of carbon tetrachloride. Ann. Univ. Mariae Curie Sklodowska. 57, 55-60. Muriel, P. and Escobr, Y. 2003. Kupffer cells are responsible for liver cirrhosis induced by carbon tetrachloride . J. Appl. Toxicol. 23, 103-108 Turkacaper, N. Bayer. S., Koyuncu, A. and Ceyhan, K. 2003. Octreotide inhidits hepatic fibrosis, bile duct proliferation and bacterial translocation in obstructive jaundice. Hepatogasroenterology. 50, 680 683. Wasmuth, H.E. Lammert, F. and Matern, S. 2003. Genetic risk factors for hepatic fibrosis in chronic liver diseases. Med. Klin. 98, 754 762
Noni Cli. Res. J. 2007, 1(1-2) 40
N. Murugesh
Uricosuric Effect of Indian Noni (Morinda citrifolia. L)
Authors affiliation : N. Murugesh Institute for Pharmacology, Madurai Medical College, Madurai, Tamil Nadu, India.
Keywords : Uric acid, gout and Noni
Abstract : Uricosuric effect of the Indian Noni was studied by an indirect method of phenol red elimination and a direct method of estimating uric acid in serum and urine in Noni fed rats. Plasma level of phenol red shows an increase in Noni fed rats which is an indirect evidence for its uricosuric effect. Direct estimation of uric acid in serum showed a decrease and that in urine showed an increase. All these effects are comparable to that of probenecid, a standard uricosuric agent. These effects are suggestive of a beneficial effect of Indian Noni in gout.
Correspondence to : N. Murugesh Institute for Pharmacology, Madurai Medical College, Madurai, Tamil Nadu, India.
Introduction
Gout is a painful type of arthritis. It attacks large and small joints. Usually it attacks one joint at a time. It is caused by high level of uric acid in blood (hyperurecaemia). Uric acid crystals collect in joints and connective tissues. (Edwards and Bouchin, 1991). Drugs used in the treatment of gout include NSAIDs, corticosteroids, uric acid synthesis inhibitors such as allopurinol, in addition to uricosuric agents like probenecid and sulphynpyrazone (Tripathi, 2003). The use of these drugs involves a variety of drug interactions and adverse effects. Noni has been advocated for a variety of joint disorders such as rhematoid arthritis, polyarthritis, juvenile arthritis etc.. Also it is much effective in gout and hence a scientific validation for this effect has been sought in this investigation by evaluating the uricosuric effect of Indian Noni.
Materials and Methods Animals

Male albino rats weighing between 150 and 175g were used. The animals were maintained under standard laboratory conditions with pellet diet and water ad libitum. Phenol red elimination Uricosuric agents delay the renal excretion of phenol red (Phenol sulphonapthalein). So plasma level of phenol red increases which is an indirect
41 Noni Cli. Res. J. 2007, 1(1-2)
N. Murugesh Uricosuric Effect of Indian Noni (Morinda citrifolia. L)
evidence for its uricosuric effect. (Vogel and Vogel, 1997). Two ml of Indian Noni was administered to a group of 6 rats orally. Thirty minutes later, 2.5ml/kg of a 3% aqueous solution of phenol red was injected through tail vein. It was followed by flushing of 2.5ml/kg of saline by the same route. Blood was collected by retroorbital puncture at 30, 60, 120 and 180 minutes and phenol red concentration estimated. Serum uric acid Serum uric acid concentration was determined by standard procedures (Varley, 1967) at 5, 10, 15 and 20 days of Noni administration at a dose of 2ml daily by oral route for 20 days. Uric acid in urine Noni fed animals (2ml daily orally for 20 days) were maintained in a metabolic cage. Urine collected was estimated for uric acid on the 5th, 10 th, 15th and 20th day. All the results were compared with probenecid, a standard uricosuric agent administered at a dose of 10mg/kg body weight by oral route.

Indian Noni is a wonderful remedy for gout and hence its uricosuric effects has been investigated for the first time in this report. Increase in phenol red concentration in plasma is an indirect evidence for its uricosuric effect. Noni produces a significant increase in plasma phenol red concentration (Fig. 1). The effect is very much comparable to that of probenecid, a standard uricosuric agent.
PHENOL RED mg/dl
NONI
TIME IN MINUTES
PROBENECID
Figure. 1. Phenol red concentration on administration of Noni and Probenecid.
Noni Cli. Res. J. 2007, 1(1-2) 42
Direct estimation of serum uric acid shows a decline in Noni fed rats (Fig. 2) and the decrease is proportional to the days of administration. Again these results are similar to those of probenecid. This decrease in serum uric acid concentration coincides with an increase in urine (Fig. 3). Contrary to phenol red estimation, these two results are direct evidences for the uricosuric effect of Indian Noni. Again, the uricosuric effect of Noni is comparable to that of probenecid. The beneficial effect of Indian Noni in gout is thus evident and it can be safely recommended for these patients since it is a natural product devoid of any adverse effects.
10 8
URIC ACID mg/dl
6 4 2 0 0 5
DAYS
10
15
NONI
20
PROBENECID
Figure. 2. Serum uric acid level on administration of Noni and Probenecid
URIC ACID mg/dl
10
DAYS
15
NONI
20
PROBENECID
Figure. 3. Uric acid concentration in urine on administration of Noni and Probenecid.
43 Noni Cli. Res. J. 2007, 1(1-2)
References
Edwards, C.R.W. and Bouchier. I.A.D. 1991. (in) Davidsons Principles and Practice of Medicine. Sixteenth Edn. ELBS with Churchill Livingstone P. 794. Tripathi, K.D. 2003. (in) Essentials of Medical Pharmacology Fifth Edn. Jaypee Brothers, New Delhi, India P. 188. Varley, H. 1967. (in) Practical Clinical Biochemistry Fourth Edn. Arnold Heinemann Publishers (India) Pvt. Ltd. New Delhi, India P. 204. Vogel, H.G. and Vogel W.H. 1997. (in) Drug Discovery and Evaluation First Edn. Springer Verlag. Berlin Heidelberg P. 180.
Noni Cli. Res. J. 2007, 1(1-2) 44
World Noni
Research Foundation
With the mission of educating the people, the World Noni Research Foundation, a nonprofit organisation dedicates itself to love and care for Morinda citrifolia., through research and development. Learning from the wisdom of the simple people, WNRF aims at working with everyone to conserve and improve Noni towards sustainable human and ecological health. It will share the Nonis past glory, ethnobotany, history, science, benefits and its multiple uses with all. The WNRF also serves as a facilitatory body for all Noni farmers, industries and consumers to establish a sustainable Noni economy network. The WNRF collectively represents the interests of all people in the Noni research and industry. It is an independent body and committed to exclusive Noni research and development. The WNRF website, journals and news letters are established to provide a non-biased forum for the researchers, consumers and industries to publicise their research findings and experiences with Morinda species. WNRF believes that this synergistic effort of scientists and people of Noni Solidarity would empower millions of ordinary masses to find their dignity and economic freedom, more naturally. This will lead to the realization of our vision Healthy people, Healthy nation in India and rest of the world. Our Programmes Focus on Conserving the Morinda species in India and rest of the world from its degradation. Organising Noni Biodiversity Action Network (NBAN) to save endangered (Red listed) Morinda species in the above regions. Developing Bioinformatics database on Morinda species existing in India and rest of the world and record all Indigenous Technical Knowledge about it. Supporting the research and development programmes on discovering the multiple potential of Morinda species in fields like pharmaceutical, nutraceutical, cosmetology, dye, agriculture, etc. Sharing the cutting edge action-programmes and research findings with researchers, farmers, consumers, food industry leaders, health - drug industry leaders, students and masses. Connecting the Morinda species researchers in India and rest of the world. Promoting the Indian Noni for health regenerative systems and processes through clinical studies & biotechnological research. Developing Noni Villages for Noni based socio-economic development of people at the grass-root level. Monitoring and encouraging quality Morinda products in the Market. Regenerating the glory of Indian Noni
Owned and Published by P.I. Peter from 85, First Main Road, Gandhi Nagar, Adyar, Chennai - 600 020. and printed by him at Reliance Printers No. 9, Sardar Patel Road, Adyar, Chennai - 600 020. Editor : P.I. Peter RNI TC No. TNENG 04409 / 19.01.05 R Dis No. : 2381/04

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Noni Clinical Research Journal

Volume 1 Numbers 1-2 January - July 2007

Editor-In-Chief Dr. Kirti Singh

Technical Editor P. Rethinam

World Noni Research Foundation

Noni Clinical Research Journal

World Noni Research Foundation

Noni Research Clinical Journal

Editorial Board Editor-In-Chief Dr. Kirti Singh

Technical Editor P. Rethinam

Clinical Research on Morinda citrifolia L. Noni Prof. P. I. Peter

Studies of Comparative Anti-HIV Activity and cytotoxicity of Morinda citrifolia L.

Effects of Noni (Morinda citrifolia L.) on Carcinoma of Breast

Price : Rs. 500 / annum US $ 20 / annum

Clinical Research on Morinda citrifolia L. Noni

Keywords : Morinda citrifolia, Xeronine, anti bacterial, antiviral, antitumor,

analgesic, anti-inflammatory, immune enhancing, cancer prevention.

Noni Cli. Res. J. 2007, 1(1-2) 4

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

Pharmacological activity of the active principles in Noni

Pharmacological Studies and medicinal uses

5 Noni Cli. Res. J. 2007, 1(1-2)

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

Preliminary medical research

Noni Cli. Res. J. 2007, 1(1-2) 6

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

Recent advances in Noni research- Biological activities of Noni

7 Noni Cli. Res. J. 2007, 1(1-2)

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

Noni Cli. Res. J. 2007, 1(1-2) 8

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

Mental health and improved high frequency

Cancer Preventive Effect of Morinda citrifolia (Noni)

9 Noni Cli. Res. J. 2007, 1(1-2)

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

Noni Cli. Res. J. 2007, 1(1-2) 10

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

11 Noni Cli. Res. J. 2007, 1(1-2)

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

Noni Cli. Res. J. 2007, 1(1-2) 12

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

13 Noni Cli. Res. J. 2007, 1(1-2)

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

Noni Cli. Res. J. 2007, 1(1-2) 14

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

15 Noni Cli. Res. J. 2007, 1(1-2)

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

Noni Cli. Res. J. 2007, 1(1-2) 16

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

17 Noni Cli. Res. J. 2007, 1(1-2)

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

Noni Cli. Res. J. 2007, 1(1-2) 18

Prof. P. I. Peter Clinical Research on Morinda citrifolia L. Noni

19 Noni Cli. Res. J. 2007, 1(1-2)

Keywords : Diabetes mellitus, Noni food supplement

Noni Cli. Res. J. 2007, 1(1-2) 20

Materials and Methods

Results and Discussion

21 Noni Cli. Res. J. 2007, 1(1-2)

OHAS : Oral Hypo Glyceamic Agents

Poor 0.90% Red

Yellow Fair 8.70%