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Noni ClinicalResearchJournal

World Noni Research Foundation# 64, Third Cross Street, Second Main Road, Gandhi Nagar

Adyar, Chennai - 600 020. IndiaE-mail : [email protected] Visit : www.worldnoni.org

Editor-In-Chief

Dr. Kirti Singh

Technical Editor

P. Rethinam

Volume 1 Numbers 1-2 January - July 2007

Noni ClinicalResearchJournal

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.

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©WNRF, 64, Third Cross Street, Second Main Road, Gandhi Nagar, Adyar, Chennai 600 020, India.

Volume 1 Number 1-2 January - July 2007

CONTENTS

REVIEW

Clinical Research on Morinda citrifolia L. – Noni

Prof. P. I. Peter

The effect of Noni (Morinda citrifolia L.) inType 2 diabetes mellitus in inadequately controlled patients

G. Sathish Kumar

Studies of Comparative Anti-HIV Activity andcytotoxicity 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 InfestationIn Vitro Study.


Anti-fibrotic effect of Noni (Morinda citrifolia. L)on carbon tetrachloride induced liver fibrosis

N. Murugesh, A.J.M. Christina and N. Chidambaranathan

Uricosuric Effect of Indian Noni (Morinda citrifolia. L)

N. Murugesh

Noni ResearchClinicalJournal

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World NoniResearch Foundation

Editorial Board

Editor-In-Chief

Dr. Kirti Singh

Technical Editor

P. Rethinam

Members

Dr. K. Mohandas

Dr. N. Murugesh

Dr. Sathish Kumar

Dr. K. Pradhan

Prof. P. I. Peter

Disclaimer :

The views expressed in thearticles are the views of theauthors and not the viewsof WNRF.

Price : Rs. 500 / annumUS $ 20 / annum

38

Clinical Research onMorinda citrifolia L. – Noni

Authors’ affiliation :

Prof. P. I. Peter85, First Main RoadGandhi Nagar, AdyarChennai - 600 020. India

Abstract : Morinda Citrifolia –Noni –family Rubiaceae has been widlyused by the people and folk healers for food and other medicinalpurposes. Traditional medical manuscripts handed down from generationto generation cite the Noni fruit as the primary ingredient in theirhealth preparation. Decades of ground breaking research reveals abroad range of therapeutic effects, including anti bacterial, antiviral,antitumor, anti helmin, analgesic, hypotensive, anti-inflammatory, immuneenhancing and cancer prevention activities. In order to encapsulate themedicinal value and therapeutic effects of the Noni fruit and tosummarize scientific evidence that supports the traditional claims aliterature review and recent advances in Noni research has beendetailed.

Keywords : Morinda citrifolia, Xeronine, anti bacterial, antiviral, antitumor,analgesic, anti-inflammatory, immune enhancing, cancer prevention.

Prof. P. I. Peter

Correspondence to :

Prof. P. I. Peter85, First Main RoadGandhi Nagar, AdyarChennai - 600 020. IndiaE-mail : [email protected]

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 bothfood and folk medicine. The recent use of noni as a dietary supplement hasincreased greatly and is reported to have a broad range of therapeutic effects,including antibacterial, antiviral, antifungal, antitumor, anthelminthetic, analgesic,hypotensive, anti-inflammatory, and immune enhancing effects. Morinda citrifolia,L., is native to South East Asia but has been extensively spread by man throughoutIndia and into the Pacific islands as far as the islands of French Polynesia, ofwhich 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, looksbright for this plant, but further studies has to be performed to discover its fullpotential.

In order to reveal the nutritional and medicinal value of the Noni plant, and tosummarize scientific evidence that supports the claim, a literature review andrecent advances in Noni research are given below.

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Pharmacological activity of the active principles in Noni

The presence of phytonutrients and vitamins in Noni can help the body fightmicrobes, help fight against inflammation, help fight carcinogens, and boost theimmune system.

The Pharmacological activity of the active principles being :

Oligo- and polysaccharides – long-chain sugar molecules that serve aprobiotic function as dietary fiber fermentable by colonic bacteria, yieldingshort chain fatty acids with numerous potential health properties .

Glycosides – sugar-phenolic compounds including flavonoids such as rutinand asperulosidic acid, are common in several Rubiaceae plants; specificallynamed noni isolates called iridoides and morindoides have been reported.

Trisaccharide fatty-acid esters, “noniosides” - result ing fromcombination of an alcohol and an acid in noni fruit, noniosides are chemicalsgiving 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 HIVviral proteins.

Alkaloids – naturally occurring amines from plants, often attributed to causingbitter tastes and so may contribute to the foul taste of noni. Some referencesmention xeronine or proxeronine as important noni constituents.

Other components being octoanoic acid, potassium, vitamin C, terpenoids,alkaloids, anthraquinones (such as nordamnacanthal, morindone, rubiadin, andrubiadin,methyl ether, anthraquinone glycoside), carotene, vitamin A, flavoneglycosides, linoleic acid, Alizarin, amino acids, acubin, L-asperuloside, caproicacid, caprylic acid, ursolic acid, rutin, and a putative proxeronine.

Xeronine system: Noni fruit contains a natural precursor for Xeronine thatwas named Proxeronine. Proxeronine is converted to the alkaloid, Xeronine, inthe body by an enzyme called Proxeroninase. Xeronine is able to modify themolecular structure of proteins. Thus Xeronine has a wide range of biologicalactivities. Xeronine will interact with the protein and make it fold into its properconformation.

Pharmacological Studies and medicinal uses

Noni is used by some cancer patients for its anti-cancer and tumor-reducingpossibilities. Some sufferers from immune-compromised diseases such as AIDS

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

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

and chronic fatigue syndrome use Noni to boost immune system function. Inresearch conducted on mice, Noni has been shown to boost the immune systemdirectly by increasing the activity of macrophages and or lymphocytes in theimmune system. In recent studies, the polysaccharides in Noni have shown toexhibit an anti-tumor effect and when taken in conjunction with chemotherapeuticagents it can help improve recovery time. People with diabetes and hypoglycemiahave reported that noni helps stabilize blood sugar levels in the body. People witharthritis, joint pain, and inflammatory conditions have used noni. It is also used asa sedative, painkiller, and sleeping aid. Noni juice is recommended to removeparasites, to cleanse the digestive tract and improve digestion, and to controlweight. It is used as a general health tonic to improve energy and resistance andto slow the effects of aging. It is also used for asthma; digestive disorders includingulcers; irritable bowel syndrome; constipation and diarrhea; and fibromyalgia, acondition 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 thatin fact Noni did demonstrate a non-toxic analgesic pain relieving effect and sedativeeffect on the mice. The researchers findings did confirm the traditional analgesicproperties and uses of the Noni plant.

Scientific Studies

A substance called ursolic acid found in the leaves of the noni plant has beenshown to have anti-cancer properties in the body. A Japanese study found thatnoni fruit contains another substance (damnacanthal) that has some effectivenessagainst pre-cancerous cells. Some evidence points to noni’s ability to increaseimmune system activity, due to substances found in the fruit (including a chemicalcalled proxeronine). The leaves of the plant contain chemicals that may lowerblood sugar levels, as well as reduce pain and inflammation. One study showedthat laboratory mice with lung cancer had much longer survival times when givennoni juice daily. A French study determined that the roots of the noni plant containnatural sedatives, while another study pointed to a compound that noni leavesmay contain that is anti-malarial and anti-parasitic in its effects. Finally, surveys ofnoni users have indicated testimonial success with the use of noni for cancer,strokes, diabetes, and as a general health and energy improver. Noni has beenshown to contain vitamins, minerals, and antioxidants.

Preliminary medical research

Over the years since 1994, noni has increasingly stimulated the interest of medicalscience, with 114 papers published since then and 36 just in 2006-7. Despite the

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


large market for juice products and research developments, the nutrient andphytochemical profiles of noni have not been extensively studied.

Furthermore, numerous health claims made in noni juice marketing are graduallysupported by scientific research and in human clinical trials. One cancer studycompleted under NIH peer-review in 2006 has been conducted, the results ofwhich 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 loweredblood cholesterol levels. Completed in 2006, however, the results of this studyhave not been published under peer-review .

Laboratory studies have investigated noni’s effect on the growth of canceroustissue in mice. One such study in vitro found that noni reduced growth of capillaryvessels sprouting from human breast tumor explants and, at increasedconcentrations, caused existing vessels to degenerate. It remains unknown whethersuch 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 (usingdetection methods of biochemical markers called DNA adducts). It further showeda reduced number of DNA adducts in rats induced with a carcinogen. The samestudy showed effective antioxidant properties of noni juice compared with thoseof vitamin C, grape seed powder, and pycnogenol. The results indicated reducedcarcinogen-DNA adduct formation in this laboratory model and antioxidant activitythat 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 otheranthraquinone compounds in Noni roots, are all proven antibacterial agents.These compounds have been shown to fight against infectious bacteria strainssuch as Pseudomonas aeruginosa, Proteus morgaii, Staphylococcus aureus,Baciillis subtilis, Escherichia coli, Salmonella, and Shigela. These antibacterialelements within Noni are responsible for the treatment of skin infections, colds,fevers, and other bacterial-caused health problems Recently, Duncan demonstratedthat scopoletin, a health promoter in Noni, inhibits the activity of E. coli, commonlyassociated with recent outbreaks resulting in hundreds of serious infections andeven death. Noni also helps stomach ulcer through inhibition of the bacteria Hpylori.

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Antiviral activity

Umezawa and coworkers found a compound isolated from Noni roots named 1-methoxy- 2-formyl-3-hydroxyanthraquinone suppressed the cytopathic effect ofHIV infected MT-4 cells, without inhibiting cell growth.

Anthelmintic activity

An ethanol extract of the tender Noni leaves induced paralysis and death of thehuman parasitic nematode worm, Ascaris Lumbricoides, within a day. A botanistvia Morton reported that Noni has been used in the Philippines and Hawaii as aneffective insecticide.

Analgesic activity

Joseph Betz reported that the Noni fruits possesses analgesic and tranquilizingactivities. A French research team led by Younos, tested the analgesic and sedativeeffects of extracts from the Morinda citrifolia plant. The extract did “show asignificant, dose-related, central analgesic activity in the treated mice.” They statedthat “these findings validate the traditional analgesic properties of this plant.” Theanalgesic efficacy of the Noni extract is 75 % as strong as morphine, yet non-addictive and side effect free. In cooperation between University of Illinois Collegeof Medicine and Henan Medical University, Wang and Fu examined the analgesicproperties of noni in animal models. NONI was tested for its analgesic propertiesby the “twisted method” animal model.

Hypotensive activity

Dang Van Ho of Vietnam demonstrated that a total extract of the Noni roots has ahypotensive effect. Moorthy and coworkers found that an ethanol extract of theNoni roots lowered the blood pressure in an anesthetized dog. Youngken’sresearch team determined that a hot water extract of Noni roots lowered theblood pressure of an anesthetized dog. A Hawaiian physician reported that Nonifruit juice had a diuretic effect.

Immunological activity

Asahina found that an alcohol extract of Noni fruit at various concentrationsinhibited the production of tumor necrosis factor-alpha (TNF-a), which is anendogenous tumor promoters. Therefore the alcohol extract may inhibit the tumorpromoting effect of TNF-a. Hirazumi found that noni contains a polysaccharide-rich substance that inhibited tumor growth. It did not exert significant cytotoxiceffects in adapted cultures of lung cancer cells, but could activate peritonealexudates 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 qualityof life in the patients with decreased bone mineral density and auditory functionhas been conducted in UIC College of Medicine, Rockford, IL. This study showedthat Noni provided a positive benefit on mental health and improved high frequencyhearing. The data suggests that increased amounts or extended duration of Noniintake 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 byepidemiological observations that the use of aspirin and other non-steroidalinflammatory drugs (NSAIDs) is associated with the reduced incidence of colonand 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 inductionin response to chemical carcinogens. It has been suggested that COX-2 overexpression may lead to increased angiogenesis and inflammatory reaction.Therefore the inhibition of COX-2 might have a general cancer preventive effectvia anti-inflammatory activity and decrease angiogenesis. In this study, the selectivityof COX-2 inhibition of Noni versus COX-1 in vitro was investigated. The discoveryof the selective COX-2 inhibition of Noni is very significant since Noni is a naturalfruit juice without side effects. This is the first scientific evidence for a strong anti-inflammatory activity in Noni, which may also be one mechanism of cancerprevention.

Cancer Preventive Effect of Morinda citrifolia (Noni)

The hypothesis that Morinda citrifolia ,L possesses a cancer preventive effect atthe initiation stage of carcinogenesis was studied. One preliminary data indicatedthat 10% Noni Juice made from Morinda citrifolia fruit in drinking water for oneweek was able to prevent DMBA-DNA adduct formation. The levels of DMBA-DNAadducts were reduced by 30% in the heart, 41% in the lung, 42% in the liver, and80% in the kidney of female SD rats. Even more dramatic results were obtained inmale C57 BL-6 mice: 10% noni was able to reduce DMBA-DNA adduct formationby 60% in the heart, 50% in the lung, 70% in the liver, and 90% in the kidney. Inorder 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 Tetrazoliumnitroblue (TNB) assays. The results suggest that prevention of carcinogen-DNAadduct formation and the antioxidant activity of noni may contribute to the cancerpreventive effect of Morinda citrifolia L.

Conclusions

Ancient folk healers used M citrifolia as one of their primary medicinal plants. Asfolk traditions have been blended with introduced cash economies, modifiedmedicinal systems have evolved. These systems are based upon bothcommercialized healers and commercialized plant-based remedies. Elements thathave contributed to the commercialization of M.citrifolia ,L., includes., keypublications and technological introductions from other cultures, and shifts fromindications with existing over-the-counter commercial products (eg, topicalantibiotics) to indications with few satisfactory over-the counter commercialproducts (eg, internal treatment of cancer, diabetes, hypertension, etc). In modernsociety, which is dominated by a bioscience paradigm, claims of efficacy need tobe linked to specific chemical causes and mechanisms of action. Without thesesupporting “scientific” findings, M citrifolia,L fruit products would probably nothave developed as rapidly as they have. It is interesting that although the rationalefor turning to natural products is to avoid perceived harshness, reduction, and“unnatural” attributes of synthetic medicinal products, people still have a desireto know why a natural product works and expect that rationale to include abioscience explanation of activity. This research may initially follow the impliedindications of the culture that developed the plant’s use. Other leads may be followedas they arise from the research process. Although there do not seem to betraditional indications for its use in lifestyle disease , M.citrifolia is offering promisein this area.

References

Zhu YP, Woerdenbag HJ . Traditional Chinese herbal medicine. Pharm World Sci1995; 17: 103-12.

Whistler WA. Traditional and herbal medicine in the cook islands. J Ethnopharm1985; 13: 239-80.

Singh Y, Ikahihifo T, Panuve M, Slatter C. Folk medicine in Tonga. A study on theuse of herbal medicines for obstetric and gynacological conditions and disorders.J Ethnopharm 1984; 12: 305-25.

Tabrah FL, Eveleth BM. Evaluation of the effectiveness of ancient Hawaiian medicine.Hawaii Med J 1966; 25: 223-30.

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


Krauss B. Plants in Hawaiian culture. Honolulu: University of Hawaii Press; 1993.p103, p252.

Whistler W. Tongan herbal medicine. Isle Botanica, Honolulu, Hawaii, 1992. p 89-90.

Bruggnecate JT. Native plants can heal your wounds. Honolulu Star-Bulletin LocalNews 1992 Feb 2.

Neal M. Gardens of Hawaii. Honolulu, Hawaii: Bishop Museum Press; 1965. p804.

Cheeseman TF. The flora of raratonga, the chief island of the cook group. v 6.London: Linnean Soc;1903. p 261-313.

Seemann B. Flora V. A des cription of the plants of the Viti or Fiji is lands with anaccount of their history, us es , and properties. London: L Reeve and Co; 1866. p1865-73.

Maiden JH. Useful native plants of Australia including Tasmania. Sydney: Tunerand Henderson Publisher; 1889. p 45.

Morton JF. The ocean-going Noni, or Indian mulberry (Morinda citrifolia,Rubiaceae) and some of its ‘colorful’ relatives. Economic Botany 1992; 46: 241-56.

Merrill ED. Noni (Morinda citrifolia) as an edible plant. In: Technical manual:emergency food plants and poisonous plants of the islands of the pacific.Washington DC: US Government Printing Office; 1943.

Abbott IA. La’au Hawaii’ traditional Hawaiian uses of plants. v 3. Honolulu, Hawaii:Bishop Museum Press; 1992. p 97-100.

Swanholm CE, St John H, Scheuer PJ. A survey of alkaloids in Hawaiian plants.Pacific Science 1959; 13: 295-305.

Solomon N. The tropical fruit with 101 medicinal uses, NONI juice. 2nd ed.Woodland Publishing; 1999.

Allen WH, London C. Some information on the ethnobotanical properties of Noni(Morinda citrifolia). In: The useful plants of india; 1873.

Abbott IA. The geographic origin of the plants most commonly used for medicineby Hawaiians. J Ethnopharmacol 1985; 14: 213-22.

Bushnell OA, Fukuda M, Makinodian T. The antibacterial properties of someplants found in Hawaii. Pacific Science 1950; 4: 167-83.

Pride Publishing, Noni: Polynesia’s natural pharmacy. 1997. p 13.

Levand O, Larson HO. Some chemical cons tituents of Morinda citrifolia. PlantaMed 1979; 36: 186-7.

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


Farine JP, Legal L, Moreteau B, Le Quere JL. Volatile components of ripe fruits ofMor inda citr ifolia and their effects on Drosophila. Phytochemistry 1996; 41:433-8.

Higa I, Fuyama Y. Genetics of food preference in Drosophila sechellia. 1. Responsesto food attractants. Genetica 1993; 88: 129-36.

Peerzada N, Renaud S, Ryan P. Vitamin C and elemental compos ition of somebushfruits. J Plant Nutrition 1990; 13:787-93.

Budavari S, O’Neil MJ, Smith A, Heckelman PE. In: The Merck Index. Anencyclopedia of chemicals, drugs , and biologicals. 11th ed. Merck & Co Inc,Rathway, New Jersey, 1989.

Moorthy NK, Reddy GS. Preliminary phytochemical and pharmacological study ofMorinda citrifolia, Linn. Antiseptic 1970; 67: 167-71.

Daulatabad CD, Mulla GM, Mirajikar AM. Riconoleic acid in Morinda citrifoliaseed oil. Oil Technologists’ Association of India 1989; 21: 26-7.

Balakrishna S, Seshadri TR, Venkataramani B. Special chemical component ofcommercial woods and related plant materials: Part X-Heartwood of Morindacitrifolia Linn. J Sci Industrial Res 1961; 20B: 331-3.

Legal L, David JR, Jallon JM. Molecular basis of Morinda citrifolia (L.): toxicity onDrosophila. J Chem Ecolog 1994; 20: 1931-43.

Singh J, Tiwari RD. Flavone glycosides from the flowers of Morinda citrifolia. JIndian Chem Soc 1976; 53: 424.

Simonsen JL. Note on the constituents of Morinda citrifolia. J Chem Soc 1920;117: 561-4.

Heinicke R. The pharmacologically active ingredient of Noni. Bulletin of theNational Tropical Botanical Garden, 1985.

Wang M, Kikuzaki H, Csiszar K, Boyd CD, Maunakea A, Fong SF, et al. Noveltrisaccharide fatty acid ester identified from the fruits of Morinda citrifolia (Noni).J Agric Food Chem 1999; 47: 4880-2.

Sang S, He K, Liu G, Zhu N, Cheng X, Wang M, et al. A new unusual iridoid withinhibition of activator protein-1 (AP-1) from the leaves of Morinda citrifolia L.Org Lett 2001; 3: 1307-9.

Sang S, Cheng X, Zhu N, Wang M, Jhoo JW, Stark RE, et al. Iridoid glycosides fromthe leaves of Morinda citrifolia. J Nat Prod 2001; 64: 799-800.

Liu G, Bode A, Ma WY, Sang S, Ho CT, Dong Z. Two novel glycos ides from the fruitsof Morinda citrifolia (noni) inhibit AP-1 transactivation and cell trans formationin the mouse epidermal JB6 cell line. Cancer Res 2001; 61: 5749-56.

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


Sang S, Cheng X, Zhu N, Stark RE, Badmaev V, Ghai G, et al. Flavonolglycosidesand novel iridoid glycoside from the leaves of Morinda citrifolia. J Agric FoodChem 2001; 49: 4478-81.

Wang M, Kikuzaki H, Jin Y, Nakatani N, Zhu N, Csiszar K, et al. Novel glycosidesfrom noni (Morinda citrifolia). J Nat Prod 2000; 63: 1182-3.

Duke JA. Handbook of phytochemicals. Boca Raton, FL: CRC Publishing; 1992.

Heinicke R. The Xeronine sys tem: a new cellular mechanism that explains thehealth promoting action of NONI and Bromelian. Direct Source Publishing; 2001.

Atkinson N. Antibacterial substances from flowering plants. 3. Antibacterial activityof dried Australian plants by a rapid direct plate test. Australian J Exper Biol 1956;34: 17-26.

Leach AJ, Leach DN, Leach GJ . Antibacterial activity of some medicinal plants ofPapua New Guinea. Sci New Guinea 1988; 14: 1-7.

Locher CP, Burch MT, Mower HF, Beres tecky J , Davis H, Van Poel B, et al. Anti-microbiol activity and anti-complement activity of extract obtained from s electedHawaiian medicinal plants. J Ethnopharm 1995; 49: 23-32.

Duncan SH, Flint HJ, Stewart CS. Inhibitory activity of gut bacteria against Escherichia coli 0157 mediated by dietary plant metabolites. FEMS Microbiol Lett1998; 164: 283-58.

Umezawa K. Isolation of 1-methoxy-2-foremyl-3-hydroxyanthraquinone from Mcitrifolia and neoplasm inhibitors containing the same. Japan Kokai Tokyo KohoJP 06 87, 736 (94-87, 736) Appl 1992; 92/264, 311 07.

American Chemical Society: Noni plant may yield new drugs to fight tuberculosis. Pressreleas e the 2000 International Chemical Congress of Pacific Basin Societies. 2000.

Author unlis ted. Noni plant may help TB. AIDS patient care STDS 2001; 15: 175.

Hirazumi A, Furusawa E, Chou SC, Hokama Y. Anticancer activity of Morindacitrifolia (noni) on intraperitoneally implanted Lewis lung carcinoma in syngeneicmice. Proc West Pharmacol Soc 1994; 37: 145-6.

Hirazumi A, Furusawa E, Chou SC, Hokama Y. Immunomodulation contributes tothe anticancer activity of Morinda citrifolia (noni) fruit juice. Proc West PharmacolSoc 1996; 39: 7-9.

Hirazumi A, Furus awa E. An immunomodulatory polysaccharide- rich substancefrom the fruit juice of Morinda citrifolia (noni) with antitumour activity. PhytotherRes 1999; 13: 380-7.

Hiramatsu T, Imoto M, Koyano T, Umezawa K. Induction of normal p henotypes inras -trans fo rmed cells by damnacanthal from Morinda citrifolia. Cancer Lett1993; 73: 161-6.

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


Hiwasa T, Arase Y, Chen Z, Kita K, Umezawa K, Ito H, et al. Stimulation of ultraviolet-induced apoptos is of human fibroblast UVr-1 cells by tyrosine kinas e inhibitors.FEBS Lett 1999; 444: 173-6.

Sang S, He K, Liu G, Zhu N, Cheng X, Wang M, et al. A new unusual iridoid withinhibition of activator protein-1 (AP-1) from the leaves of Morinda citrifolia L.Org Lett 2001; 3: 1307-9.

Raj RK. Screening of indigenous plants for anthelmintic action againsthumanAscaris Lumbricoides: Part-II. Indian J Physiol Pharmacol 1975; 19: 47-9.

Younos C, Rolland A, Fleurentin J, Lanhers MC, Miss lin R, Mortier F. Analgesicand behavioural effects of Morinda citrifolia. Planta Med 1990; 56: 430-4.

Youngken HW, Jenkins H J, Butler CL. Studies on Morinda citrifolia L. II. J AmPharm Assoc 1960; 49: 271-3.

Youngken HW. A study of the root of Morinda citrifolia Linn, I. J Am Pharm Assoc1958; 47: 162-5.

Davison C. Hawaiian medicine. The Queen’s Hospital Bulletin with Palama ClinicSection 1927; 4: 2-5.

Asahina AY, Ebesu JSM, Ichinotsubo D, Tongson J, Hokama Y. Effect of okadaicacid (OA) and Noni fruit extraction in the synthesis of tumor necrosis factor-a(TNF-a) by peripheral blood mononuclear (PBN) cells in vitro. The Procedingsof the International Symposium of Ciguatera and Marine Natural Products; 1994.p 197-205.

Hokama Y. The effect of Noni fruit extract (Morinda citrifolia, Indian mulberry)on thymocytes of BALB/c mouse. FASEB J 1993; 7: A866.

Langford J , Doughty A, Wang MY, Clayton L, Babich M. Effects of Morinda citrifoliaon auditory function and quality of life in patients with decreas ed bone mineraldensity and auditory function. J Complementary & Alternative Med Submitted,2002.

Acute oral toxicity s tudy in rats -limit test: TAHITIAN NONI® Juice. 1999 Oct 6.Product Safety Labs (Eurofins Scientific, Inc). East Brunswick, New Jersey, USA.

Kaaber K. TAHITIAN NONI® Juice: active systemic anaphylaxis test in the guineapig. 2000 Feb 18 . Scantox Biologisk Laboratorium A/S, DK-426, Lille Skensved,Denmark.

Guinea pig antigenicity study. TAHITIAN NONI® juice. 2000 Feb 29. ProductSafety Labs (Eurofins Scientific, Inc). East Brunswick, New Jersey, USA.

Glerup P. TAHITIAN TNJ: A 13-week oral (gavage) toxicity study in rats. 2001 May.Scantox Biologisk Laboratorium A/S, DK-426. Lille Skensved, Denmark.

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


Degener O. In: Plants of Hawaii national park illustrative of plants and cus toms ofthe 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.Sturtevant’s notes on edible plants (Hedrick U.P, editor). Albany, New York: JBLyon 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, NewZealand. 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. Nature’s amazing healer, Noni. Pleas ant Grove, Utah: WoodlandPublishing; 1998.

Solomon N. The Noni phenomenon. Discover the powerful tropical healer thatfights cancer, lowers high blood pres sure and relieves chronic pain. Direct SourcePublishing; 1999.

Solomon N. TAHITIAN NONI Juice: How much, how often, for what. Direct SourcePublishing; 2000.

Solomon N. TAHITIAN NONI® Juice—The pain fighter (arthritis/pain). DirectSource Publishing; 2001.

Sharps J. NONI juice, A pres cription for the good health. Integrated Health Service;2000.

Veith I. Translated “Yellow Emperor’s Classic of Internal Medicine” (2500 BC); 2002.

Du B, You S. Present situation in preventing and treating liver fibrosis with TCMdrugs. 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 ofcohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000 343:78-85.

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


Perera P. Molecular epidemiology and prevention of cancer. Environ HealthPerspect 1995; 103 (Suppl 8): 2336.

American Ins titute for Cancer Research: 11th Annual Research Conference onDiet, Nutrition and Cancer. Washington DC. 2001.

Rus so J , Russo IH. Experimentally induced mammary tumors in rats . BreastCancer Res Treat 1996; 39: 7-20.

elSisie AE, Hall P, Sim WL, Earnest DL., Sipes IG. Characterization of vitamin Apotentiation of carbon tetrachlorideinduced liver injury. Toxicol Appl Pharmacol1993; 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: biomarkersfor cohort selection and modifiable endpoint in chemoprevention trials. J CellBiochem Suppl 1996; 25: 85-91.

Rabes HM. DNA adducts and cell cycle. J Cancer Res Clin Oncol 1986; 112: 189-95.

Hemminki K. DNA adducts , mutations and cancer. Carinogenesis 1993; 14: 2007-12.

Poirier MC, Weston A. Human DNA adduct measurements: state of the art. EnvironHealth Perspect 1996; 104 Suppl 5:883-93.

Slaga TJ. Multistage skin carcinogenesis: an useful model for the s tudy of thechemopreventionn of cancer. Acta Pharmacol Toxicol 1984; 55 Suppl 2: 107-24.

Wang MY, Anderson G, Nowicki D. Preventive effect of Morinda citrifolia (Noni) atthe initiation s tage of mammary breas t cancer induced by 7,12-dimethylbenz(a)-anthracen (DMBA) in female Sprague-Dawley rats. The Proceedings of theFrontiers in cancer prevention research, AACR, Boston, 2002 Oct 17.

Wang MY, Nowicki D, Anderson, G. Protective effect of Mor inda citr ifolia onhepatic injury induced by a liver carcinogen. The Proceedings of 93rd AnnualMeeting of American Association for Cancer Research 2002; 43: 477.

Wang MY, Su C, Nowicki D, Jensen J, Anderson G. Morinda citrifolia and cancerprevention. J Nutrition 2001; 131 (11S):3151S.

Pryor WA. Cigarette smoke radicals and the role of free radicals in chemicalcarcinogenicity. Environ Health Perspect 1997; 105 Suppl 4: 875-82.

Bartsch H, Nair J . New DNA-das ed biomarkers for oxidative stress and cancerchemoprevention studies. Eur J Cancer 2000; 36:1229-34.

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


Wang MY, Lieher, JG. Induction by estrogens of lipid peroxidation and lipidperoxide derived malondialdehyde- DNA adducts in male Syrian hams ters : roleof l ipid peroxidat ion in estrogen-induced kidney carcinogenesis.Carcinogenesis1995; 16: 1941-5.

Diplock AT, Charleux JL, Crozier-Willi G, Rice-Evans C, Roberfroid M, Stahi W, etal. Functional food science and defense against reactive oxidative species. Br JNutr 1998; 80 Suppl 1: S77-112.

Weisburger JH, Rivenson A, Garr K, Aliaga C. Tea, or tea and milk, inhibit mammarygland and colon carcinogenesis in rats . Cancer Lett 1997; 114: 323-7.

Nishikimi M, Rao NA, Yagi K. The occurrence of superoxide anion in the reactionof reduced phenazine methosulfate and molecular oxygen. Biochem Biophys ResCommun 1972;46: 849-54.

Auerbach BJ , Kiely JS, Cornicell JA. A spectrophotometric microtiter-based assayfor 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 NYAcad Sci 2001; 952: 161-8.

Wang MY, Su C. Cancer preventive effect of Morinda citrifolia. The proceedings ofthe Strang International Cancer Prevention Conference. 2000 Nov 10-11, NewYork.

Wang MY, Su C, Nowicki D, Jensen J, Anderson G. Protective effect of Morindacitrifolia in carbontetrachloride-induced liver injury model: A light and electronmicroscopic s tudy. The Proceedings of the Eicosanoids and other Bioactive Lipidsin Cancer, Inflammatory and Related Diseas es, the 7th Annual Conference, 2001Oct 16. Loews Vanderbilt Plaza, Nashville, Tennessee, USA.

Burns DM. Cigarette smoking among the elderly: disease consequences and thebenefits of cess ation. Am J Health Promot 2000; 14: 357-61.

Meerson FZ, Kagon VE, Kozolov YP, Belkina IM, Penko A. The role of lipidperoxidation in pathogenes is of ischemic damage and the antioxidant protectionof the heart. Basic Res Cardiol 1982; 77: 465-85.

Chow CK. Cigarette smoking and oxidative damage in the lung. Ann NY Acad Sci1993; 686: 289-98.

US Department of Health and Human Services. Reducing the health consequencesof 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.

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


Hemminki K, Kumar R, Bykov VJ, louhelainen J, Vodicka P. Future researchdirections 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 peroxdation-induced putative malondialdehyde- DNA adducts in human breast tissues. CancerEpidemology, 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 theAmerican Institute for Cancer Research, 1997.

Fontham ET. Protective dietary factors and lung cancer. Int J Epidemiol 1990;19Suppl 1:S32-42.

Wang MY, Nowicki D, Anderson G, Su C, Jensen J. Protective effects of Morinda citrifoliaon plasma superoxides (SAR) and lipid peroxides (LPO) in current smokers. TheProceedings of XIth Biennial Meeting of the Society for Free Radical ResearchInternational. July 16-20, 2002. Ren’e Des cartes University. Paris, France. in press.

Natarajan K, Mori N, Artemov D, Bhujwalla ZM. Exposure of human breast cancercells to the anti-inflammatory agent indomethacin alters choline phospholipidmetabolites and Nm23 expression. Neoplasia 2002; 4:409-16.

Yao M, Song DH, Rana B, Wolfe MM. COX-2 selective inhibition revers es thetrophic 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 COX-2 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-inflammatorydrugs on overall risk of common cancer: case-control study in general practiceresearch databas e. BMJ 2000; 320: 1642-6.

Decensi A, Cos ta A. Recent advances in cancer chemoprevention, with emphasison breast and colorectal cancer. Eur J Cancer 2000; 36: 694-709.

Schreinemachers DM, Everson RB. Aspirin use and lung, colon, and breast cancerincidence 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 Sci2002; 323: 181-8.

Dermond O, Ruegg C. Inhibition of tumor angiogenesis by non-steroidal anti-inflammatory drugs : emerging mechanisms and therapeutic perspective. DrugResist Updat 2001; 4: 314-21.

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


Marrogi AJ, Travis WD, Welsh JA, Khan MA, Rahim H, Tazelaar H, et al. Nitric oxidesynthase, cyclooxygenase 2, and vascular endothelial growth factor in theangiogenesis 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 watchthis this space. Stroke 2002; 33: 2139-40.

Komoike Y, Takeeda M, Tanaka A, Kato S, Takeuchi K.. Prevention by parenteralaspirin of indomethacin-induced gastric lesions in rats: mediation by salicylicacid. Dig Dis Sci 2002; 47: 1538-45.

Koki AT, Masferrer JL. Celecoxib: a specific COX-2 inhibitor with anticancerproperties. Cancer Control 2002; 9 (2 Suppl): 28-35.

Horton JK, Williams AS, Smith-Phillips Z, Martin RC, O’Beirne G. Intracellularmeasurement of prostaglandin E2: effect of anti-inflammatory drugs on cyclooxygenase activity and prostanoid expression. Anal Biochem 1999; 271:18-28.

Su C, Wang MY, Nowicki D, Jensen J, Anderson G. Selective COX-2 inhibition ofMorinda citrifolia (Noni) in vitro. The proceedings of the Eicosanoids and otherbioactive lipids in cancer, inflammation and related disease. The 7th AnnualConference, 2001 Oct 14-17. Loews Vanderbilt Plaza, Nashville, Tennessee, USA.

Zhang LD, Zhang YL, Xu SH, Zhou G, Jin SB. Traditional Chinese medicine typingof affective disorders and treatment. Am J Chin Med 1994; 22: 321-7.

Chang IM. Anti-aging and health-promoting constituents derived from traditionaloriental herbal remedies: information retrieval using the TradiMed 2000 DB. AnnNY 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 traditionalChinese medicine. Nutrition Rev 1996; 54: S11-6.

Cheng TO. Hippocrates , cardiology, Confucius and the yellow emperor. Int JCardiol 2001; 81: 219-33.

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


The effect of Noni (Morinda citrifolia L.)in Type 2 diabetes mellitus ininadequately controlled patients


G. Sathish KumarJehovah Raphah’sDiabetic Centre,41/B, Vasavi Nagar,Kharkhana, Secunderabad,Andhra Pradesh, India - 500 015.

Abstract : The proper management of diabetes mellitus has assumedgreat importance in recent years in view of the steady increase in itsprevalence all over the world including the USA and India. Apart fromthe suffering it causes to the individual in terms of morbidity,mortality, and decrease in quality of life, the economic costs oftreating diabetes and the losses caused by decrease in productivity area major source of worry to society and organizations concerned withpublic health. Both genetic and environmental factors are implicated inthe causation of Type 2 diabetes. Among environmental factors; overeating decreased physical activity and obesity, cigarette smoking, increasedoxidant stress, and inflammatory processes have been associated, eitheras a cause, or an effect of the developing diabetic state. Patientsdiagnosed with Type 2 diabetes milletus for at least 5 years, who arecurrently on insulin and not adequately controlled with current treatment,with HbA 1c> 8%. Present study highlights how patients inadequatelycontrolled with an existing insulin treatment and Oral HypoglasmicAgents (OHS). By adding Noni as a food supplement significantimprovement in HbA 1c and FBG is observed after 6 months follow-up.

Keywords : Diabetes mellitus, Noni food supplement

G. Sathish Kumar

Correspondence to :

G. Sathish KumarJehovah Raphah’sDiabetic Centre,41/B, Vasavi Nagar,Kharkhana, Secunderabad,Andhra Pradesh, India - 500 015.

Introduction

World Health Organization states that India and Asia Pacific regions continue tobe at the forefront of diabetes mellitus epidemic, with consequences to healthwhich threaten to be devastating. Younger members of our communities are notspared from the disease, with a significant problem emerging in the urbanizedyoung in the most affluent parts of our country. Lifestyle changes and urbanizationappear to be the underlying causes of this problem, the current number of peoplewith diabetes in South East Asia is estimated to be 40 million, and this number willincrease to at least 81.5 million by 2025.

However, there is irrefutable evidence that diabetes can be prevented or delayedin people at high risk and that the progression of many of the complicationsassociated with diabetes can be halted. Appropriate diet and physical activity,

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

maintaining a healthy body weight, refraining from tobacco smoking, and propercontrol of diabetes and blood pressure in people with diabetes will help preventdiabetes and reduce its complications. Each country needs to develop appropriateguidelines for the prevention and control of diabetes, and set up systems to ensurethat these guidelines are adhered to. There is a need to establish the diagnosticcriteria and classification, followed by target treatment of diabetes.

The United Kingdom prospective diabetes study (UKPDS) showed that intensivetreatment can decrease the morbidity and mortality of the disease by decreasingits chronic complications. However, the majority of patients with a longer durationof diabetes remain poorly controlled with oral agents, and the use of insulin,which could improve glyceamic control, is often long delayed and not aggressiveenough. There is also limited information regarding next step therapy options forpatients with diabetes who fail to achieve or maintain adequate glyceamic controlwith current treatment.

Materials and Methods

The study was done using randomized design with double blind (OHA’s + Insulin/OHA’s + Noni) and Control - (only OHA’s) for 24 weeks.

A total of 305 patients attending the diabetic clinic for treatment were enrolled forthis study. After a running in period of 3 months, the patients were randomizedeither to the control or to the study groups and followed up for next 6 monthsfrom 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 insulinsensitivity improve C-peptide levels and improvement in fasting blood lipids, wereobserved (Heinicke 2001; Schecter S 1999)

G. Sathish Kumar The effect of Noni (Morinda citrifolia L.) in Type 2 diabetes mellitus in inadequately controlled patients

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

PinkGreen

Yellow

Red

Good 34.30%

Poor 0.90%

Excellent55.90%

Fair 8.70%

Table. 1 Investigations and blood parameters.

Outcome Contro (OHA’S) OHA’S + Insulin OHA’S + Noni

Fasting Plasma Glucose (mg/dl)

Baseline 223.2 223.2 230.4

Week 4 248.4 201.6 190.8

Week 16 248.4 183.6 165.6

Week 24 237.6 172.8 111.6

HDL Cholestrol(mg/dl)

Baseline 35.20 35.5 30.80

Week 8 37.10 40.6 40.80

Week 16 37.10 40.8 40.0

Week 24 37.10 46.8 50.0

LDL Cholestrol(mg/dl)

Baseline 125.2 121.6 125.4

Week 8 125.2 118.8 120.4

Week 16 125.2 116.0 109.0

Week 24 120.0 112.0 97.0

OHAS : Oral Hypo Glyceamic Agents

Fig. 1. Investigators over all Openion on Noni Treatment


Noni Cli. Res. J. 2007, 1(1-2) 22

Table 2. Investigator’s over all opinion on Noni Treatment

Opinion N (%)

Excellent 55.90%

Good 34.30%

Fair 08.70%

Poor 0.90%

Fig. 2 Percentage of Patients showed 1% or higher A1C reduction.

OHA’s and Noni are effective in achieving glycemic goal.

Discussions : The study group showed a statistically significant better compliancethan the control group on all parameters, Indian Noni, in patients with type 2diabetes showed that, when used as a combination therapy (noni), this agentslowers fasting and postprandial glucose in patients with type 2 diabetes. The authorsfound Noni to be safe and well tolerated. Indian Noni proves definitely improvesthe quality living of the patients.

Xeronine, the alkaloid of Noni in the presence of insulin activates the peripheralcell 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 tobalance blood glucose levels.

Noni modifies the body immune system to keep the sensitivity of beta cells intactand body develops resistance to many diseases.

Noni helps in reducing anxiety, lessens the stress, response to some extent byelevating serotonin levels in blood.

50

45

40

35

30

25

20

15

10

5

0OHA + Insulin Placebo OHA + Noni

%


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

In this research on diabetic practice, it was learnt that several micronutrients arenormally deficient in patients with full blown diabetes.

Noni, rich in antioxidants and micronutrients which are essential for all the diabeticpatients. (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 formedicine by Hawaiians. J. Ethnopharmacol 14 : 213-22.

Annonymous., 1990. WHO Study Group Diet, Nutrition and Prevention of ChronicDiseases, Geneva : World Health Organisation.

Heinicke., R. 2001. The Xeronine system a new cellular mechanism that explainsthe 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-Nature’s True Adaptogen from the South Pacific, TotalHealth, Vol 21.2

Shaprs., J. 2000. Noni Juice, A prescription for the good health. Integrated HealthService, 2000.

Solomon., N. 1999. The tropical fruit with 101 medicinal uses, Noni Juice. 2nded. Woodland Publishing US 1999.


Noni Cli. Res. J. 2007, 1(1-2) 24

Studies of Comparative Anti-HIV Activity andcytotoxicity of Morinda citrifolia L.


Periyasamy SelvamNarayanan MurugeshMyriam WitvrouwArulmigu Kalasalingam College ofPharmacy, Krishnankoil, 626 190,IndiaInstitute of Pharmacology, MaduraiMedical College, Madurai-625 020,IndiaMolecular Medicine, KatholiekeUniversiteit-Leuven and IRCKULAK,Kapucijnenvoer 33, B-3000Leuven, Flanders, Belgium.

Abstract : Fruit juice and ethanol, methanolic extract of fruit powderof Morinda citrifolia (MC) have been studied against the replication ofHIV-1(IIIB) in MT-4 cells. Fruit juice of Morinda citrifolia (MC)exhibited a maximum protection of 18% of the cells against thecytopathic effect of HIV-1(IIIB) strain and displayed marked cytotoxicactivity in lymphocyte (MT-4) cells (CC50: 0.19 mg/ml). However theethanol (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 µg/ml, respectively.

Keywords : Anti-HIV Activity, cytotoxicity and Morinda citrifolia

Periyasamy SelvamNarayanan MurugeshMyriam Witvrouw

Correspondence to :

Periyasamy SelvamArulmigu Kalasalingam College ofPharmacy, Krishnankoil, 626 190,IndiaEmail :[email protected]

Introduction

Acquired immuno deficiency syndrome (AIDS) is a life threatening and debilitatingdisease state caused by retrovirus infection, and the etiologic agent is now widelyknown as the human immunodeficiency virus type 1. Many compounds of plantorigin have been identified that inhibit different stages in the replication cycle ofHIV (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 Polynesiansfor 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 al2002). The present study is designed to determine the antiviral activity of fruitjuice and ethanolic (EMC) and methanolic (MMC) extract of Morinda citrifolia(MC) against the replication of HIV-1(III

B) in MT-4 cells and Cytotoxicity in mock-

infected 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 subjectedto hot continuous percolation using methanol and ethanol. The methanol (MMC)and ethanol (EMC) extract of Morinda citrifolia were concentrated by distillationand used for screening.

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

Anti-HIV Assay. Morinda citrifolia was tested for its inhibitory effects against thereplication of HIV-1(III

B) in MT-4 cells (Pauwels et al, 1988; Witvrouw et al,

2004). The MT-4 cells were grown and maintained in RPMI 1640 DM Mediumsupplemented with 10% (v/v) heat-inactivated Fetal Calf Serum (FCS), 2 mM-glutamine, 0.1% Sodium bicarbonate and 20mg/ml gentamicin (culture medium).Inhibitory effect of MC on HIV-1 replication was monitored by inhibition of virus-induced 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 extractsof MCT. MT-4 cells were added at a final concentration of 6x105 cells/ml. After 5days of incubation at 37°C, 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 MTTmethod.


The anti-HIV data are presented in Table 1.

Table1. Anti-HIV (IIIB) Activity and Cytotoxicity of Morinda citrifolia

in MT-4 cells

Compound EC50

a (µg/ml) CC50

b (µg/ml) Maximum % Protection

MC >0.19 0.19 18

EMC >72.34 72.34 0

MMC >220 220 0

AZT (STD) 0.0062 65.65 106

a 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 beenevaluated 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 maximumprotection of 18% of the MT-4 cells against the cytopathic effect of HIV-1(III

B)

after acute infection. Morinda citrifolia displayed marked cytotoxic activity inlymphocyte (MT-4) cells (CC

50: 0.19 mg/ml). Both ethanol (EMC) and methanol

extracts (MMC) displayed cytotoxic activity (CC50

) in lymphocyte (MT-4) cells at72.34 and 220 µg/ml respectively.

Periyasamy Selvam et al. Studies of Comparative Anti-HIV Activity and cytotoxicity of Morinda citrifolia L.

Noni Cli. Res. J. 2007, 1(1-2) 26

Acknowledgement

We acknowledge A. Nijs and B. Van Remoortel for excellent technical assistance.We thank the NIH AIDS Research and Reference Reagent Programme, Division ofAIDS, NIAID for providing the HIV-1(III

B) strain and MT-4 cells. Work at KULeuven

is supported by the European Commission (CSHB-CT-2005-505480).World NoniResearch foundation for financial support. Author is grateful to Dept of Scienceand Technology for award of BOYSCAST fellowship for this research work.

References

Hans R. 1994. Studies on the anti-leukemia activity of Indigofera tinctoria. Stemcell, 12: 53-63.

Hu K, Kobayashi H, Dong A, Iwasaki S, Yao X. 2000. Antifungal, antimitotic andanti-HIV-1 agents from the roots of Wikstroemia indica. Planta Med. 66:564-7.

Muruganandhan AV, Battacharya SK, Ghosal S. 2000. Indole and flavanoidconstituents of Wrightia tinctoria. Indian J Chem, 39B, 125-131.

Pauwels R, Balzarini J. Baba M, Snoeck R, Schols D, Herdewijn P, Desmyter J, DeClercq E. 988. Rapid and automated tetrazolium-based colorimeteric assay fordetection 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 fromGlycyrrhiza lepidota Phytochemistry. 58:153-7.

Shahidul Alam M, Quader MA, Rashid MA. 2000. HIV-inhibitory diterpenoid fromAnisomeles 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: implicationsfor treatment and postexposure prophylaxis. Antiviral Therapy, 9: 57-65.

Wu PL, Lin FW, Wu TS, Kuoh CS, Lee KH, Lee SJ. 2004. Cytotoxic andanti-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 Noniresearch. Acta Pharmacol Sin. 2002 Dec;23(12):1127-41.

Periyasamy Selvam et al. Studies of Comparative Anti-HIV Activity and cytotoxicity of Morinda citrifolia L.

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

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


Dr. Rangadhar SatapathyMIG – II, 6/2, BDA colony,Chandrasekharpur,Bhubaneswar, Orissa, India

Abstract : Breast cancer is the fifth most common cause of cancerdeath (after lung cancer, stomach cancer, liver cancer, and coloncancer). In 2005, breast cancer caused 502,000 deaths (7% of cancerdeaths; almost 1% of all deaths) worldwide. Among women, breastcancer is the most common cause of cancer death. The mainstay ofbreast cancer treatment is surgery when the tumor is localized, withpossible adjuvant chemotherapy, and/or radiotherapy. Depending onclinical criteria (age, type of cancer, size, metastasis) patients areroughly divided in to high risk and low risk cases, with each riskcategory following different rules for therapy. Treatment possibilitiesinclude radiation therapy, chemotherapy, hormone therapy, and immunetherapy. Nothing guarantees that you won’t develop breast cancer. Thereare lots of side effects of chemotherapy and radiotherapy that makesthe patient worse than cancer itself. Indian Noni helps to overcomemaximum side effects of all cancer cases including the breast cancerby its immune enhancing and nutritive supplementing property. It alsocontains many bio anti carcinogenic ingredients that helps by enhancingthe efficacy of the cancer treatment too. It acts as a tool for primaryprevention, secondary prevention and as an adjuvant immune enhancingsupplement with the common line of cancer treatment.

Keywords : Carcinoma, Morinda citrifolia anticarcinogenic agents.


Correspondence to :


Introduction

Breast cancer, the second-leading cause of cancer deaths in India, is thedisease women fear most. Breast cancer can also occur in men. Today, radicalmastectomy is rarely performed. Most breast lumps aren’t cancerous. Yet themost common sign of breast cancer for both men and women is a lump orthickening in the breast. Often, the lump is painless. In breast cancer, some ofthe cells in the breast begin growing abnormally. These cells divide morerapidly 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 ofbreast cancer begins in the milk-producing ducts, but cancer may also beginin the lobules or in other breast tissue. In most cases, it isn’t clear what causes

Noni Cli. Res. J. 2007, 1(1-2) 28

normal breast cells to become cancerous. Doctors do know that only 5 percentto 10 percent of breast cancers are inherited. Treatments exist for every typeand 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 dependmainly on the type and extent of the treatment. Side effects of breast cancerradiation therapy —including uncommon side effects that may involve theheart, lungs, and ribs. One of the common side effects of breast cancer radiationtreatment is fatigue, especially in the later weeks of treatment and for sometimeafterward. The side effects of chemotherapy depend mainly on the drugs thepatient receives. As with other types of breast cancer treatment, side effects varyfrom person to person. In general, anticancer drugs affect rapidly dividingcells. 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 byanticancer drugs, patients are more likely to get infections, bruise or bleedeasily, 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 otherside effects, such as loss of appetite, nausea, vomiting, diarrhea, or mouthsores.

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 usedas a chemo-immunotherapy agent to treat cancer. NONI-ppt present in NONIdevelops an anti-tumor response by stimulating the release of various cytokinesmediator 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 andmutation of the malignant cells

Dr. Rangadhar Satapathy Effects of Noni (Morinda citrifolia) on Carcinoma of Breast

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

Pretreatment with Noni followed by ultraviolet irradiation increased the levelsof phosphorylated extra cellular signal-regulated kinases (ERK) and stress-activated protein kinases (SAPK) enzymes in the body. Activation of SARK andERKs plays an important role in triggering apoptosis. Thus their activationproves the stimulatory effect of Noni on ultraviolet-induced apoptosis. ThusNoni can be used as an immune supplemental therapeutic agent with anycancer therapy.

Noni exhibits antiangiogenesis effects on the malignant cells.

The cancer tumor has the ability to develop its own blood vessels around it toget 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 antiangiogenesiseffect on the malignant cells thus inhibiting the growth and mutations of thesecells and induces program cell death or apoptosis..

Epigallocatechin gallate (EGCg)- EGCg is a polyphenolic flavonoid antioxidantthat 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 reactwith oxygen to generate reactive oxygen species (ROS), the free radical formsof oxygen that damage the DNA of cell.

The ROS is involved in mutations and tissue damage in diseases such as cancerand rheumatoid arthritis. Normal amounts of NOX production are important toregulate the cell growth. It is generally inactive during the normal cell divisionprocess, in response to growth hormone stimulation but it is active in cancerouscells and responsible for the cancerous cell proliferation, cell motility, invasionand 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. Morre’s experimental studies it is found that EGCg in Noniinhibits NOX carcinogenesis activity but does not inhibit the NOX activity ofhealthy cells.

Noni prevents the carcinogen DNA adduct formation on cell

Noni Prevents DNA adduct formation, and hence protects the cell from convertingto cancer. Hence Noni can be used for primary and secondary prevention ofcancer.

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 cellwill be responsible for mutation and consequent cancer development. Thereforepreventing carcinogen-DNA adduct formation is a key step for primary preventionin cancer at the initiation of carcinogenesis.

Noni helps to check the carcinogen DNA adduct formation. Hence it mayprevent 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 excessivefree radicals are allowed to exist near the nucleus of cell, significant damageto the DNA of cell can result. Free radicals can also wreck damage on thegenetic 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 newlydeveloped cell. When there is further oxidative stress to this mutated DNA ofthe 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 truecancer.

Oxidative stress is indeed the cause of cancer and antioxidants used to bringfree radical back into balance would lower the risk of cancer. Therefore thebet strategy is to maximize your own body’s immune system and antioxidantdefense and this begins by eating a healthy natural suppliment that rich withantioxidants. Noni is the rich source of antioxidants. The high anti oxidantproperty of Noni helps to prevent the formation of carcinogen-DNA adducts. Itwas hypothesized that the antioxidants in Noni may have cancer protectiveeffects by scavenging reactive oxygen free radicals and quenching lipid peroxides.In vitro study shows that the Damnacanthal, one phytochemical present in Nonihave 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 liverand small bowel, thereby decreasing the damaging effects of carcinogens.Animal studies demonstrated that dietary limonene present in Noni reducedmammary tumor growth.

Noni inhibits Matrix metalloproteinases (MMPs) enzyme

Matrix metalloproteinases (MMPs), the enzyme have been identified as keyplayers in tumor invasion and metastasis. Excessive MMPs secretion has beenregarded 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 thatstabilize connective tissue by inhibiting the enzymatic digestion of collagenfibers. Vitamin C is essential for production of collagen and acts as a powerfulantioxidant by scavenging free radicals and thereby protects cells from damage.Epigallocatechin gallate (EGCG) has antioxidant and anticancerogenicproperties. It prevent cancer cell invasion by inhibiting MMPs. The naturalamino acid lysine, especially in combination with vitamin C and other selectedcellular nutrients, is capable of blocking this ‘collagen digestion’. Noni containsthe above two amino acids lysine and proline. Noni is rich with vitamin C. Nonicontain the phytochemical Epigallocatehin gallate (EGCG). Hence Noni shouldhelp to prevent the cancer tumor invasion and metastasis.

Limonene, the phytochemical present in Noni increases the levels of liverenzymes involved in detoxifying carcinogens.

Many recent studies have shown that elevation of phase II enzymes, such asNAD(P) H : quinone reductase (QR) and GST, correlates with protection againstchemical - induced carcinogenesis in animal models, in the stage of promotionas well as initiation. Noni fruits contain an extremely potent quinone reductaseinducer, 2 - methoxy - 1,b,6 - trihydroxyanthraquinone. This new anthraquinonewas nearly 40 times more potent than any other quinone.

Noni contain many glycosides

Noni contains many glycosides. Asperuloside is a glycoside. Traditionally, thisglycoside has been used for diurises. Research has indicated that it is also ananticlastogenic (that is, prevents the breakage of chromosomes). As a result,it is anti-mutagenic or resists mutation within the cell’s 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 fromcarcinoma of breast. Her condition was pretty worse before 4 months. Thewhole right breast and axillary portion had severe swelling with radiating painfrom breast to axial and back. There was a big nodular hard mass inside theright breast. Her treating physician sent her for the FNAC report of that portionand it was detected cancer of breast. She was advised for the operation as thecancer 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 takingNoni for three months her hard nodular mass softened and gradually reducedin 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 nowcontinuing Noni internally as well as applying Noni externally.

Conclusion

Current treatment protocols with chemotherapy and / or radiation althoughbeneficial, is toxic and has the potential to destroy healthy cells as well. Ourapproach has been to develop strategies to inhibit cancer development,progression and metastasis using naturally occurring nutrients, which arerelatively non-toxic. Indian Noni is one among them. It contains the entiremajor 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 protocolit will cover maximum side effects of chemotherapy or radio therapy; acts asan immune supplemental adjuvant to the current therapy; as it prevents theDNA adduct formation it help in primary prevention and secondary preventionfor all cancer patient or those with family history of cancer treatment.

References

Su BN, Pawlus AD, Jung HA, Keller WJ, McLaughlin JL, Kinghorn AD. Potentantioxidants found in Noni. Source: Program for Collaborative Research in thePharmaceutical Sciences, Department of Medicinal Chemistry andPharmacognosy, 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 2002Acta Pharmacol Sin Dec; 23 (12): 1127-1141. Morinda citrifolia (Noni): Aliterature review and recent advances in Noni research. WANG Mian-Ying, BrettJ WEST, C Jarakae JENSEN, Diane NOWICKI, SU Chen, Afa K PALU, GaryANDERSON. University of Illinois College of Medicine, Department of Pathology,1601 Parkview Avenue, Rockford, IL 61107, USA; Department of R & D, MorindaInc, Provo, Utah 84606, USA.


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

Effect of Noni on Filarial WormInfestation In Vitro Study

Abstract : Lymphatic Filariasis is a parasitic and infectious tropicaldisease, caused by the thread-like parasitic filarial worms, Wuchereriabancrofti, Brugia malayi, and Brugia timori, all transmitted bymosquitoes. The most spectacular symptom of lymphatic filariasis iselephantiasis (thickening of the skin and underlying tissues), whichwas the first disease discovered to be transmitted by insects. Elephantiasisis caused when the parasites lodge in the lymphatic system. Elephantiasisaffects mainly the lower extremities, whereas ears, mucus membranes,and amputation stumps are rarely affected; however, it depends on thespecies of filaria. W. bancrofti can affect the legs, arms, vulva, breasts,while Brugia timori rarely affects the genitals. One vitro study showedthat the adult parasite of Wuchereria bancrofti died within 20 hoursin the culture media mixed with Noni in comparison to the controlgroup which survived for 60 hours without adding Noni. Similarlyextract of Noni induces paralysis and death of parasitic nematode wormof the human Ascaris Lumbricoides, within a day. A botanist viaMorton, botanist reported that Noni has been used in the Philippinesand Hawaii as an effective insecticide. Hence it can be suggested toprescribe Noni along with other medication of the filariasis.

Keywords : Noni higher concentration and filarial worm.

Introduction

It has been shown that Noni has anti helminthic effect on Round worm (Ascarisumbricoids). Noni has been used in the Philippines and Hawaii as an effectiveanti-parasitic. On that basis an invitro study of the effects of Noni juice on bothadult and microfilaria of cattle parasite Setaria digitata has been conducted.Lymphatic Filariasis is a parasitic and infectious tropical disease, caused by threethread-like parasitic filarial worms, Wuchereria bancrofti, Brugia malayi, andBrugia timori, all transmitted by mosquitoes

The signs and symptoms: lymph adenoma, massive leg swelling, elephantiasis,lymphangitis, fever, pain epididymitis, orchitis, eosinophilia, etc.




Correspondence to :


Noni Cli. Res. J. 2007, 1(1-2) 34

With the objective to evaluate the effect of Noni on different stages of filarial parasitesa 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 filarialparasites were collected from the local slaughter house.

2. Collection of Microfilaria: Adult parasites were cut into different pieces in theISCOV medium and kept at 37° C for an hour. Microfilaria were harvested aftercentrifuging at 10‘000 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 37°C in ISCOVmedium 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 werefiltered through 25 micron filter before adding to the culture medium.

Control group of parasites were cultured in the medium without Noni that isnamed C

1. Effects of Noni on adult parasite was studied an in vitro in 3 groups of medium.

Medium and groups

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.4. 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.

Dr. Rangadhar Satapathy Effect of Noni on Filarial Worm Infestation In Vitro Study

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

At day 3 (after 48 hrs) some parasite of Gr-1 and Gr-2 were dead and the rest ofthem 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-2were found dead without any movement.

At day four (after 72 hrs) the microfilaria in both the Gr-1 and Gr-2 were founddead 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 higherconcentrations within 48 hours.

Dr. Rangadhar Satapathy Effect of Noni on Filarial Worm Infestation In Vitro Study

Noni Cli. Res. J. 2007, 1(1-2) 36

Anti-fibrotic effect of Noni (Morindacitrifolia. L) on carbon tetrachlorideinduced liver fibrosis


N. MurugeshA.J.M. ChristinaN. ChidambaranathanInstitute 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.

Abstract : A study was carried out to investigate the effect of Noniagainst carbon tetrachloride (CCl4), induced liver fibrosis. Liver fibrosiswas 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 liverfibrosis was assessed by the content of hydroxyproline in liver, serumlevel of asparate transaminase (AST), alanine transaminase (ALT),alkaline phosphatase (ALP) and bilirubin. Treatment with Noni reducedthe hydroxyproline content of liver, serum enzyme levels and totalbilirubin. These observations confirm the antifibrotic effect of extract.

Keywords : Morinda citrifolia L. , Antifibrolic effect liver

N. MurugeshA.J.M. ChristinaN. Chidambaranathan

Correspondence to :

N. MurugeshInstitute for Pharmacology,Madurai Medical College, Madurai,Tamil Nadu, India.

Introduction

Fibrosis is seen as a scar formation in liver (Borchers et. al., 2000). Hepaticfibrosis 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 liverfibrosis. Numerous chemicals and drugs can harm the liver (Chojkier and Brenner,2003). In many experimental fibrotic models, CCl4 was used to induce hepaticinjury (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 inthe pathogenesis of liver fibrosis (George, et. al., 2004). Likewise, bile duct ligationtechnique was used by many workers to induce fibrosis (Kountouras, J., et. al.,1984; Turkacaper, N., et. al., 2003).

In this study CCl4 induced liver fibrosis was used as a model to evaluate theantifibrotic effect of Noni.


Animals

Male albino Wistar rats (150 –200 g) were purchased from Chellamuthu Trust,Madurai. They were housed in groups of 3 to 4/cage, maintained at 25 + 20Cunder 12 hour light -dark cycle. They were fed with standard pellet diet and waterad libitum.

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

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 bodyweight mixed with an equal volume of corn oil (Bickel, et. al., 1991). Three daysafter the last dose, rats were sacrificed under light anesthesia and blood and liversamples 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 28days. For comparison a group of normal rats was used throughout. The bodyweight 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 wascollected by cardiac puncture. A part of it was used for biochemical estimationand centrifuged at 3000 rpm to obtain serum. The levels of asparate transaminase(AST), alananine transaminase (ALT), alkaline phosphatase (ALP) and totalbillirubin were estimated by standard procedures.

Determination of Hydroxyproline content in liver

The hydroxyproline content of liver was determined by the method suggested byJamall, et. al., (1981). The specimens of liver were weighed and hydrolysedcompletely in 6 M HCl. A fraction of the sample was derivatised using ChloramineT solution and Erhlich’s reagent. The density was measured at 558 nm.

Statistical analysis

The values are expressed as mean +SEM. The data were analysed using one wayANOVA followed by Newman Keul’s 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 treatedwith CCl4

Treatments AST IU/L ALT/IU/L ALP IU/L Total Bilirubin mg/dl

Normal rats 159 +6 47+ 2.2 215 + 6.8 0.48 + 0.01

CCL4treated rats 289 +1.1* 102 +5* 396+8* 1.6 + 0.08*

CCL4 + Nonitreated rats 175+ 8*a 61+4*a 235 +13.2*a 0.7 +0.03*a

N. Murugesh et al. Anti-fibrotic effect of Noni (Morinda citrifolia. L) on carbon tetrachloride induced liver fibrosis

Noni Cli. Res. J. 2007, 1(1-2) 38

Data are mean + SEM. n=6, Newman Keul’s 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 followingvarious treatments

Treatment Hydroxyproline Liver weight on day 28Content (mg/g liver)

Normal rats 53 + 3 3.5 + 0.02

CCL4 treated rats 124 +7 4.5 + 0.06

CCL4 + Noni treated rats 77 + 3 *a 3.8 + 0.07 *a

Data are mean + SEM. n = 6, Newman Keul’s multiple test was used (P<0.05)

* significantly different from normal rats.*a significantly different from CCl4 treated rats.

Serum parameters

Treatment with CCl4 altered various tissue and serum parameters and also thearchitecture of liver. In CCl4 treated rats, the serum parameters AST, ALT, and ALPwere significantly elevated. The bilirubin level was also high. However, in CCl4 +Noni treated rats, the serum levels of these enzymes and bilirubin were significantlylow when compared to CCl4 alone treated rats.

Tissue parameters

The main tissue parameters assessed were hydroxyproline content and weight ofliver. Hydroxyproline was elevated following CCl4 treatment. Treatment with theextract reduced this parameter. Liver weight was increased in CCl4 treated ratswhich was reduced by Noni.

Discussion

Large literature states that collagen content in the extracellular matrix is high infibrosis, the extent of which could be assessed by the hydroxyproline content(Muriel and Escobar, 2003). Many earl ier studies have reported highhydroxyproline content in association with liver fibrosis. Present study showed ahigh hydroxyproline content in CCl4 treated rats, indicating the development offibrosis, which was brought down by co-treatment with Noni.

In the present study, CCl4 the toxicant that injures liver is converted totrichloromethyl 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 levelsof serum AST, ALT, ALP and bilirubin in CCl4 treated rats. The rats treated with CCl4

+ Noni showed low levels of AST, ALT, ALP and bilirubin. These observationssuggest that Noni is effective against CCl4 induced liver fibrosis in rats.

Conclusion

This study has indicated the protective effect of Noni against CCl4 induced chronicliver injury. This conclusion was based on the correction of serum as well astissue parameters by Noni.

References

Bickel, M. Baader, E. and Brocks, D.G. 1991. Beneficial effect of inhibitors ofprolyl 4-hydroxylase in CCl4 induced fibrosis of liver in rats. J. Hepatol. 13, 26-33.

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 N-nitroso 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 determinenanogram levels of 4-hydroxyproline in biological tissues . Anal. Biochem. 112,70-75.

Kountouras, J. Billing, B.H. and Seheuer, P.J. 1984 . Prolonged bile ductobstruction. 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 onrat 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 cirrhosisinduced by carbon tetrachloride . J. Appl. Toxicol. 23, 103-108

Turkacaper, N. Bayer. S., Koyuncu, A. and Ceyhan, K. 2003. Octreotide inhiditshepatic fibrosis, bile duct proliferation and bacterial translocation in obstructivejaundice. Hepatogasroenterology. 50, 680 – 683.

Wasmuth, H.E. Lammert, F. and Matern, S. 2003. Genetic risk factors for hepaticfibrosis in chronic liver diseases. Med. Klin. 98, 754 – 762


Noni Cli. Res. J. 2007, 1(1-2) 40

Uricosuric Effect of Indian Noni(Morinda citrifolia. L)

Abstract : Uricosuric effect of the Indian Noni was studied by anindirect method of phenol red elimination and a direct method ofestimating uric acid in serum and urine in Noni fed rats. Plasma levelof phenol red shows an increase in Noni fed rats which is an indirectevidence for its uricosuric effect. Direct estimation of uric acid inserum showed a decrease and that in urine showed an increase. Allthese effects are comparable to that of probenecid, a standard uricosuricagent. These effects are suggestive of a beneficial effect of Indian Noniin gout.

Keywords : Uric acid, gout and Noni

Introduction

Gout is a painful type of arthritis. It attacks large and small joints. Usually it attacksone joint at a t ime. I t 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 touricosuric agents like probenecid and sulphynpyrazone (Tripathi, 2003). Theuse of these drugs involves a variety of drug interactions and adverse effects. Nonihas 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 ascientific validation for this effect has been sought in this investigation by evaluatingthe uricosuric effect of Indian Noni.


Animals

Male albino rats weighing between 150 and 175g were used. The animals weremaintained under standard laboratory conditions with pellet diet and water adlibitum.

Phenol red elimination

Uricosuric agents delay the renal excret ion of phenol red (Phenolsulphonapthalein). So plasma level of phenol red increases which is an indirect



N. Murugesh

Correspondence to :


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

evidence for its uricosuric effect. (Vogel and Vogel, 1997). Two ml of Indian Noniwas 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 byflushing of 2.5ml/kg of saline by the same route. Blood was collected by retro-orbital puncture at 30, 60, 120 and 180 minutes and phenol red concentrationestimated.

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 byoral route for 20 days.

Uric acid in urine

Noni fed animals (2ml daily orally for 20 days) were maintained in a metaboliccage. Urine collected was estimated for uric acid on the 5th, 10th, 15th and 20th day.

All the results were compared with probenecid, a standard uricosuric agentadministered at a dose of 10mg/kg body weight by oral route.


Indian Noni is a wonderful remedy for gout and hence its uricosuric effects hasbeen investigated for the first time in this report. Increase in phenol redconcentration in plasma is an indirect evidence for its uricosuric effect. Noniproduces a significant increase in plasma phenol red concentration (Fig. 1). Theeffect is very much comparable to that of probenecid, a standard uricosuric agent.

Figure. 1. Phenol red concentration on administrationof Noni and Probenecid.

NONI

PROBENECIDTIME IN MINUTES

PHEN

OL

RED

mg/

dl

N. Murugesh Uricosuric Effect of Indian Noni (Morinda citrifolia. L)

Noni Cli. Res. J. 2007, 1(1-2) 42

Direct estimation of serum uric acid shows a decline in Noni fed rats (Fig. 2) andthe decrease is proportional to the days of administration. Again these results aresimilar to those of probenecid. This decrease in serum uric acid concentrationcoincides 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. Thebeneficial effect of Indian Noni in gout is thus evident and it can be safelyrecommended for these patients since it is a natural product devoid of any adverseeffects.

DAYS

UR

IC A

CID

mg/

dl

Figure. 2. Serum uric acid level on administration of Noni andProbenecid

UR

IC A

CID

mg/

dl

DAYS

Figure. 3. Uric acid concentration in urine on administrationof Noni and Probenecid.

NONI

PROBENECID

NONI

PROBENECID

0 5 10 15 20

10

8

6

4

2

0100 5 10 15 20


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

References

Edwards, C.R.W. and Bouchier. I.A.D. 1991. (in) Davidson’s Principles andPractice of Medicine. Sixteenth Edn. ELBS with Churchill Livingstone P. 794.

Tripathi, K.D. 2003. (in) Essentials of Medical Pharmacology Fifth Edn. JaypeeBrothers, 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

Owned and Published by P.I. Peter from 85, First Main Road, Gandhi Nagar, Adyar, Chennai - 600 020. andprinted 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

With the mission of educating the people, the World Noni Research Foundation, a non-

profit 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 Noni’s 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

World Noni Research Foundation

noni clinical research journal - ..:: welcome to noni … issue_1.pdfnoni clinical research journal...

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