ANTIPYRETIC ACTIVITY OF AQUEOUS AND ALCOHOLIC EXTRACTS OF NONI ON YEAST INDUCED PYREXIA IN RATS

ANTIPYRETIC ACTIVITY OF AQUEOUS AND ALCOHOLIC EXTRACTS OF NONI ON YEAST INDUCED PYREXIA IN RATS

Bharti Jethani ¹, R. K. Sharma*², M. Raipuria ¹, Hemlata Jain ³

Department of Pharmacology and Toxicology, College of Veterinary Science and Animal Husbandry ¹, Mhow, Madhya Pradesh, India

Department of Pharmacology and Toxicology, College of Veterinary Science and Animal Husbandry ², Jabalpur, Madhya Pradesh, India

Animal Biotechnology Centre, Madhya Pradesh Pashu Chikitsa Vigyan University, Jabalpur ³, Madhya Pradesh, India

ABSTRACT

Numerous herbal agents have been claimed to having antipyretic property. One up-coming botanical fruit of Morinda citrifolia, whose Polynesian name is Noni, is unique in view of the large number of medical indications that characterize claims for its efficacy. Researchers at an independent research facility found that Noni was a selective inhibitor of COX-2 enzyme. The analgesic efficacy of the Noni extract is 75 % as strong as morphine. Thus the present study was planned to study the antipyretic activity of aqueous & alcoholic extracts of Noni on yeast induced pyrexia, a model for experimentally induced pyrexia in albino rats. The alcoholic extract of Noni has been found to produce more significant antipyretic activity after 2^nd, 3^rd and 4^th hours of administration.

Alcoholic Extract

INTRODUCTION: Over the past few years natural products have become increasingly popular and the field of natural herbal remedies has flourished to a great extent. One up-coming botanical fruit of Morinda citrifolia, whose Polynesian name is Noni, is currently the subject of much science, myth, and marketing hype. Noni, as it is called in the Hawaiian language, is also called the great morinda and Indian mulberry.

The fruit has a pungent aroma when ripening and is often called “cheese fruit” or “vomit fruit”. It is hoped that scientific evaluation of many potential medicinal plant extracts may provide safe and broad spectrum herbal formulations. As a result of adverse effects of NSAID, the use of these drugs as anti-inflammatory and antipyretic agents has not been successful in all cases.

Morinda citrifolia, a small tree grows predominantly along the tropical coasts. It have already been reported that Noni have antibacterial, antiviral, antifungal, antitumor, antidiabetes, analgesic, anti-inflammatory and immune enhancing activities ^{1, 2}. Morinda citrifolia was extensively used in folk medicine by the Polynesians for over 2000 years ³. The fruit of Noni is claimed to prevent and cure several diseases ⁴. Noni is the best source of anti oxidant. It is the best nutritional supplement & works at cellular level.

It improves efficacy of medicines & supports immune system, circulatory system, digestive system & metabolic system. A number of major components have been identified in the Noni plant such as potassium, vitamin C, anthraquinones, β-sitosterol, carotene, vitamin A, flavone glycosides, linoleic acid, caproic acid, ursolic acid and rutin. Researchers at an independent research facility found that Noni was a selective inhibitor of COX-2 enzyme ⁵. The analgesic efficacy of the Noni extract is 75 % as strong as morphine, yet non-addictive and side effect free ⁶. It has been reported to possess anti-inflammatory, analgesic and anti-ulcerogenic properties.

In the present study an indigenous medicinal plant Morinda citrifolia (Noni) was evaluated to its antipyretic activities. The study conducted to explore with aqueous and alcoholic extracts of Noni on experimentally induced pyrexia in rats.

MATERIALS AND METHODS: The experiment was conducted on 36 healthy adult albino rats of either sex, weighing between 120-150g. The rats were procured from small animal section of Vet. College HISSAR and maintained in polypropylene cages and housed in the lab animal section of the department under standard managemental conditions. Rats were fed standard ration ad libtum and free access to clean water. De-worming was done before the start of experiment by praziquantel @ 1 tablet per 10 kg body weight, single dose.

Treatment groups: Before experimentation rats were fasted overnight but water was given ad libitum. The experiment was conducted in six groups of rats consisting of six rats in each group. The rats were administered the aqueous and alcoholic extracts of Noni orally in graded doses of 250, 500, 1000 mg/kg body weight. In pyretic rats, aqueous and alcoholic extracts of Noni was administered orally, the model of experiment was as follows-

Group I- Aqueous extract of Noni (250 mg /kg bwt. orally)

Group II- Aqueous extract of Noni (500 mg/kg bwt. orally)

Group III- Aqueous extract of Noni (1000 mg/kg bwt. orally)

Group IV- Alcoholic extract of Noni (250 mg /kg bwt. orally)

Group V- Alcoholic extract of Noni (500 mg/kg bwt. orally)

Group VI- Alcoholic extract of Noni (1000 mg/kg bwt. orally)

Induction of pyrexia: The rats were individually caged in a room maintained at the constant temperature of 25 °C. Normal rectal temperature was recorded by a Telethermometer and its hourly variation was noted over a period of 4 hours at the beginning of the experiment. The pyrexia was produced according to the method of Gujral et al. ⁷. A suspension of 15 percent dried Brewers yeast and 2 percent gum acacia in normal saline was injected subcutaneously. The volume injected was 1.0 ml of suspension per 100 gm of body weight. A stabilized temperature was recorded in 18 hours.

Data collection and Statistical analysis: The antipyretic activity of aqueous and alcoholic extracts of Noni was studied after administering the drugs, orally to a group of rats in graded doses of 250,500 and1000 mg/kg body weight .The antipyretic effect was studied on yeast induced pyrexia in rats. In pyretic rats, the rectal temperature was recorded at hourly interval for a period of 4 hours after administration of the drug. The data obtained during study were analyzed, employing Completely Randomized Design (CRD) as described by Snedecor and Cocharan ⁸.

RESULTS AND DISCUSSION: A phyto-therapeutic approach to modern drug development can provide many invaluable drugs from traditional medicinal plants. It is hoped that scientific evaluation of many potential medicinal plant extracts may provide safe and broad spectrum herbal formulations. The adverse effects of NSAIDS such as induced by opiates, the use of these drugs as antipyretic and analgesic agents have not been successful in all cases.

This stimulated the search for new compound possessing potent antipyretic activity with least toxic effect. The efforts in the present study have been concentrated to find out the effect of Morinda citrifolia (Noni) an indigenous medicinal plant to explore the antipyretic properties.

Pyrexia occurs due to the imbalance between the heat production and loss. The bacterial endotoxins and other pyrogens, like yeast, act by inducing the enzyme cyclooxygenase which ultimately leads to the biosynthesis and release of endogenous pyrogens by neutrophils and other cells. The endogenous pyrogen, which is known to be prostaglandin E, acts upon the hypothalamic thermoregulatory centre to set the thermostat at a higher point, with the result the rate of heat production increases and heat loss decreases leading to pyrexia. The role of prostaglandins in pyrexia was reported by Feldberg and Myres ⁹.

The antipyretic activity of aqueous and alcoholic extracts of Noni on yeast induced pyrexia in rats was studied.  The drug was administered orally to a group of rats in graded doses of 250,500 and1000 mg/kg body weight. Both aqueous and alcoholic extracts of Noni at doses 250 mg/kg did not showed any significant antipyretic activity. However aqueous extracts of Noni at doses 500 mg/kg showed a significant decrease in pyretic temperature, the decrease being from 102.73°F ± 0.09 to 101.21°F ± 0.02, 100.13°F ± 0.01 and 100.06°F ± 0.02 in 2^nd, 3^rd and 4^th hours of treatment respectively. Aqueous extracts of Noni at doses 1000 mg / kg also showed a significant decrease in pyretic temperature, the decrease being from 102.82 °F ±0.05 to 100.47°F ± 0.09 and 100.07°F ± 0.01 in 2^nd and 3^rd hours of treatment respectively (Table 1).

TABLE 1: ANTIPYRETIC ACTIVITY OF ORALLY ADMINISTERED AQUEOUS AND ALCOHOLIC EXTRACTS OF NONI ON YEAST INDUCED PYREXIA

Each treatment consists of six rats; Means in a particular class (row) with different superscripts differ significantly from each other; Means of a particular class (row) with at least one alphabet as common superscripts do not differ significantly from each other

Alcoholic extracts of Noni at doses 500 mg / kg also showed a significant decrease in pyretic temperature, the decrease being from 102.70°F ± 0.09 to 100.38°F ± 0.04 and 100.03°F ± 0.01 in 2^nd and 3 ^rd hours of treatment respectively. Alcoholic extracts of Noni at doses 1000 mg / kg showed a significant decrease in pyretic temperature from first hour onwards, the decrease being from 102.76°F ±0.09 to 101.14°F ± 0.02, 100.06°F ± 0.02 and 100.01°F ± 0.25 in 2^nd, 3^rd and 4^th hours of treatment respectively (Figure- 1). The analysis of variance revealed that there was significant (P< 0.01) difference in antipyretic activity at different time intervals in different treatment (Table-2). Alcoholic and aqueous extracts of Noni at graded doses showed significant antipyretic action.

FIG. 1: ANTIPYRETIC ACTIVITY OF ORALLY ADMINISTERED NONI ON YEAST INDUCED PYREXIA

The results indicated that the peak antipyretic effects of aqueous and alcoholic extracts of Noni were produced after 2^nd hours of their administration. Both the extracts showed their dose dependent antipyretic activity. The alcoholic extracts of Noni exhibited maximum antipyretic activity at the dose rate of 1000 mg/kg body weight as compared to equivalent doses of aqueous extract. The appreciable antipyretic effect noticed at 500 mg/kg was comparable to standard drug aspirin. The temperature decreases from 40.1°C in 0 hour to 38.2°C in 1.5^th hour and 37.5°C in 2^nd hour respectively.

TABLE 2: ANALYSIS OF VARIANCE FOR ANTIPYRETIC ACTIVITY OF ORALLY ADMINISTERED AQUEOUS AND ALCOHOLIC EXTRACTS OF NONI ON YEAST INDUCED PYREXIA

NS: non significant; ** = Indicate treatment have significant antipyretic effect at P< 0.01

The dose dependent antipyretic property was observed in another member of family Rubaicae, Benincasa hispida. Its ethanolic extract produced significant (P<0.05) antipyretic effect in dose dependent manner ¹⁰. Similarly, the methanolic extract of C. febrifuga caused a dose-dependent decrease in rectal temperature (25, 50, 100 mg/kg). The effect became significant at 30 and 60 min at the highest dose of 100 mg/kg which was 38.38 in 0 hour to 37.3 in 30 min and 37.6 in 60 min respectively ¹¹. All these findings suggest the huge scope of herbal plant for pyrexia treatment.

CONCLUSION: In the recent years, there is an increasing interest in the search for potential drugs, especially of plant origin, that are capable of masking the untoward side effects of steroidal and non-steroidal drugs. In present study the aqueous and alcoholic extracts of Noni were investigated for their antipyretic activity. This experimental investigation was carried out in albino rats of either sex weighing 120-150 g, to elucidate the mechanism of action of Morinda citrifolia (Noni).

The aqueous and alcoholic extracts of Noni have also shown dose related antipyretic and analgesic activity. Both the aqueous and alcoholic extracts of Noni significantly reduced the yeast induced pyrexia starting from 1 hour post administration and it was completely brought back to normal within 4 hour post administration. The alcoholic extract @ 1000 mg/kg produced better antipyretic action as compared to aqueous extract at the same dose rate up to 3 ^rd hr of administration.

ACKNOWLEDGEMENT: The authors are thankful to the Dean, College of Veterinary Science and Animal husbandry, Mhow for providing research facilities and WNRF, Chennai for financial support and free supply of fruits.

REFERENCES:

1. Surendiran G and Mathivanan N: An over view of the potentials of Morinda citrifolia. In Proceedings of First National Symposium on Noni Research 2006; Scientific Session V. October 7-8.
2. Wang MY, West BJ, Jensen  CJ, Nowicki  D, Su  C, Palu AK and Anderson G:. Morinda citrifolia (Noni): a literature review and recent advances in Noni research. Acta Pharmacologica Sinica 2002; 23:1127-1141.
3. Samy J, Sugumaran M and Lee LW: Herbs of Malaysia: an introduction to the medicinal, culinary, aromatic and cosmetic use of herbs. Federal Publications, Times Ed. 2005; 154-155.
4. Yanine CB, Fabrice VA, Perez M, Reynes M, Brillouet JM and Brat P: The Noni fruit (Morinda citrifolia): A review of agricultural research, nutritional and therapeutic properties. Journal of Food Composit Analysis 2006; 19:645-654.
5. Su C, Wang MY, Nowicki D, Jensen J and 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, Loews Vanderbilt Plaza, Nashville, Tennessee, USA. 2001; Oct 14-17.
6. Younos C, Rolland A, Fleurentin J, Lanhers MC, Misslin R and Mortier F: Analgesic and behavioral effects of Morinda citrifolia. Planta Medica 1990; 56:430-434.
7. Gujral ML, Kohali RP, Bhargava KP and Saxena PN: An experimental study of some drugs on temperature in normal and pyretic rats. Indian Journal of Medical Research 1956; 43:89.
8. Snedecor GW and Cochran WG: Statistical Method. IOWA State College Press, Eighth edition 1994.
9. Feldberg W and RD Myres: Temperature changes produced by amines injected in to the cerebral ventricles during anaesthesia. Journal of Physiology 1964; 175:464.
10. Qadrie ZL, Hawisa N, Khan MWA, Samuel M and Anandan R: Anti nociceptive and antipyretic activity of Benincasa Hispida in wistar albino rats. Pakistan Journal of Pharmaceutical Sciences 2009; 22(3):287-290.
11. Salawu OA, Chindo BA, Tijani AY and Adzu B: Analgesic, anti-inflammatory, antipyretic and antiplasmodial effects of the methanolic extract of Crossopteryx febrifuga. Journal of Medicinal Plants Research 2008; 2(8): 213-218.