Parasitology Research 2011, 109(5), 1351-1360 Gedunin and Photogedunin of Xylocarpus granatum possess antifilarial activity against human lymphatic filarial parasite Brugia malayi in experimental rodent host a Sweta Misra, a Meenakshi Verma, b Sunil Kumar Mishra, b Shishir Srivastava, b Vijai Lakshmi and a Shailja Misra-Bhattacharya * Divisions of Parasitology a and Medicinal and Process Chemistry b , Central Drug Research Institute, M. G. Marg, Lucknow (U.P.) 226001, India * Corresponding author: Dr. Shailja Misra-Bhattacharya FAX: +91-522-2623405/2623938/2629504, phone: +91-522-2612411-18 PABX 4221/4224, E mail: shailja_cdri@rediffmail.com/shailjacdri@yahoo.com Abstract The present study is aimed to evaluate antifilarial activity of Xylocarpus granatum (fruit from Andaman) against human lymphatic filarial parasite Brugia malayi in vivo. The in vitro antifilarial activity has already been reported earlier for this mangrove plant which has traditionally been used against several ailments. Aqueous ethanolic crude extract, four fractions (Ethyl acetate fraction, n-butanol fraction, water soluble fraction and water insoluble fraction) and pure molecule/s of Xylocarpus granatum (fruit) were tested in vitro on adult worms and microfilariae (mf) of B. malayi and the active samples were further evaluated in vivo in B. malayi i.p. transplanted jird model (Meriones unguiculatus) and Mastomys coucha subcutaneously infected with infective larvae (L3). The crude aqueous ethanolic extract was active in vitro (IC50: adult=15.46 µg/ml; mf=13.17 µg/ml) and demonstrated 52.8% and 62.7% adulticidal and embryostatic effect on B. malayi respectively in mastomys at a dose of 5x250 mg/kg by oral route. The antifilarial activity was primarily localized in the ethyl acetate soluble fraction which revealed IC50 of 8.5 and 6.9 µg/ml in adult and mf respectively. This fraction possessed moderate adulticidal and embryostatic action in vivo in mastomys. Out of eight pure molecules isolated from the active fraction, two compounds Gedunin (IC50=0.239, CC50=212.5, SI=889.1) and Photogedunin (IC50=0.213, CC50=262.3, SI=1231.4) at 5x100 mg/kg by subcutaneous route revealed excellent adulticidal efficacy resulting in to the death of 80 % and 70 % transplanted adult B. malayi in the peritoneal cavity of jirds respectively in addition to noticeable microfilaricidal action on the day of autopsy. The findings reveal that the extract from the fruit Xylocarpus granatum contains promising in vitro and in vivo antifilarial activity against human lymphatic filarial parasite B. malayi which could be attributed to the presence of two pure compounds Gedunin and Photogedunin. Key words: Brugia malayi, mastomys, jird, Gedunin, Photogedunin, Xylocarpus granatum, antifilarial, macrofilaricidal. Introduction Human lymphatic filariasis a vector-borne disease mainly caused by Wuchereria bancrofti, Brugia malayi and Brugia timori continues to cripple population in the tropical and subtropical countries. Wuchereria bancrofti, the predominant filarial parasite, affects more than 90% of lymphatic filarial patients, causing acute and chronic morbidity (Ottesen 2000). The activity of mainstay antifilarial drugs Diethylcarbamazine and ivermectin in combination with albendazole or alone is largely restricted to microfilaricidal activity. Threat of resistance to mainstay drugs is worrisome as the evidence is already revealed in various veterinary infections. Hence there is an urgent need of new and potent drug which may either kill the adult parasite or adversely affect the reproductive potential of adult worms in addition to killing of microfilariae. The traditional systems of medicine provide an extremely vast body of source material for the development of new drugs and therefore have attracted researchers. Several natural products had earlier proved themselves against many species of filarial infections e.g. Andrographis paniculata caused 100% mortality of Dipetalonema reconditum microfilariae, rhizome of Zingiber officinale (Zingiberaceae) reduced Dirofilaria immitis microfilariae load (Dutta and Sukul 1987), extract from the bark of Streblus asper was effective on chronic stages of filarial infection (Singh and Ram 1988), extracts prepared from Carapa procera, Polyalthia suaveolens and Pachypodanthium staudtii exhibited microfilaricidal activity on