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 X. 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 (intraperitoneally) i.p. transplanted in the 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 5 × 50 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 μg/ml, CC50 = 212.5 μg/ml, SI = 889.1) and photogedunin (IC50 = 0.213 μg/ml, CC50 = 262.3 μg/ml, SI = 1231.4) at 5 × 100 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 microfilaricidalo action on the day of autopsy. The findings reveal that the extract from the fruit X. 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.
Similar content being viewed by others
References
Alam MA, Sarder M, Awal MA, Sikder MMH, Daulla KA (2006) Antibacterial activity of the crude ethanolic extract of Xylocarpus granatum stem barks. Bangl J Vet Med 4(1):69–72
Alvi KA, Crews P, Aalbersberg B, Prasad R (1991) Limonoids from the Fijian medicinal plant dabi (Xylocarpus). Tetrahedron 47:8943–8948
Bandaranayake WM (2002) Bioactivities, bioactive compounds and chemical constituents of mangrove plants. [Review article]. Wetlands Ecology and Management 10:421–452
Chopra RN, Nayar SL, Chopra IC (1956) Glossary of Indian medicinal plants. CSIR, New Delhi
Chou FY, Hostettmann K, Kubo I, Nakanishi K, Taniguchi M (1977) Isolation of an insect antifeedant N-methylflindersine and several benz[c]phenanthridine alkaloids from East African plants; a comment on chelerythrine. Heterocycles 7(2):969–977
Cui J, Ouyang J, Dengb Z, Lin W (2008) Structure elucidation of an unprecedented alkaloid and a new limonoid from Xylocarpus granatum. Magn Reson Chem 46:894–897
Du SJ, Qin ZH, Wang MA, Zhu W, Han CR, Bi HP (2007) GC-MS analysis of the essential oils from Xylocarpus granatum. J Hainan Normal Univ 20(4):247–250
Du S, Wang M, Zhu W, Qin Z (2009) A new fungicidal lactone from Xylocarpus granatum (Meliaceae). Natural Product Res 23:1316–1321
Dutta A, Sukul NC (1987) Antifilarial effect of Zingiber officinale on Dirofilaria immitis. J Helminthol 61(3):268–270
Hogg RW, Gillian FT (1984) Fatty acids, sterols and hydrocarbons in the leaves from eleven species of mangrove. Phytochemistry 23:93–97
Lakshmi V, Gupta P (2008) An overview of the genus Xylocarpus. Nat Prod Res 22(14):1197–1224
Lakshmi V, Srivastava S, Mishra SK, Misra S, Verma M, Misra-Bhattacharya S (2009) In vitro and in vivo antifilarial potential of marine sponge, Haliclona exigua (Kirkpatrick), against human lymphatic filarial parasite Brugia malayi. Parasitol Res 105:1295–1301
Lakshmi V, Singh N, Shrivastva S, Mishra SK, Dhamani P, Mishra V, Palit G (2010) Gedunin and photogedunin of Xylocarpus granatum show significant anti-secretory effects and protect the gastric mucosa of peptic ulcer in rats. Phytomedicine 17:569–574
McCall JW, Malove JB, Hyong-Sun A, Thompson PE (1973) Mongolian jirds (Meriones unguiculatus) infected with Brugia malayi by the intraperitoneal route. A rich source of developing larvae, adult filariae and mf. J Parasitol 59(3):436
Misra S, Chatterjee RK, Sen AB (1984) The response of Litomosoides carinii to antifilarial agents in cotton rat Sigmodon hispidus and multimammate rat (Mastomys natalensis). Indian J Med Res 7:749–752
Misra-Bhattacharya S, Katiyar D, Bajpai P, Tripathi RP, Saxena JK (2004) 4-Methyl-7-(tetradecanoyl)-2 H-1-benzopyran-2-one a novel DNA topoisomerase II inhibitor with adulticidal and embryostatic activity against sub-periodic Brugia malayi. Parasitol Res 92:177–182
Mukherjee M, Misra S, Chatterjee RK (1998) Development of in vitro screening system for assessment of antifilarial activity of compounds. Acta Trop 70(3):251–255
Mulholland DA, Taylor DAH (1992) Limonoids from Australian members of Meliaceae. Phytochem 31:4163–4166.
O’Brien J, Wilson I, Orton T, Pognan F (2000) Investigation of the alamar blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem 267(17):5421–5426
Omar S, Godard K, Ingham A (2003) Antimalarial activities of gedunin and 7-methoxygedunin and synergistic activity with dillapiol. Ann Appl Biol 143:135–141
Ottesen EA (2000) The global programme to eliminate lymphatic filariasis. Trop Med Int Hlth 5:591–594
Petranyi G, Mieth H, Leitner I (1975) Mastomys natalensis as an experimental host for Brugia malayi subperiodic. Trop Med Publ Hlth 6(3):328–337
Ramirez B, Bickle Q, Yousif F, Fakorede F, Mouries M, Nwaka S (2007) Schistosomes: challenges in compound screening. Expert Opin Drug Discov 2(suppl 1):S53–S61
Rouf R, Uddina SJ, Shilpi JA, Alamgir M (2007) Assessment of antidiarrhoeal activity of the methanol extract of Xylocarpus granatum bark in mice model. J Ethanopharmacol 109:539–542
Shinoda Y, Ogisu M, Iwata S, Tajima T (1985) Chemical composition of mangroves II. Gifu Daigaku Nogakubu Kenkyu Hokoku 50:155–165
Singh VK, Ram ER (1988) Filaria and its herbal cure. New Botanist 15:201–205
Singh U, Misra S, Murthy PK, Katiyar JC, Agarwal A, Sircar AR (1997) Immunoreactive molecules of Brugia malayi and their diagnostic potential.Serodiag Immunother. Infect Dis 8:207–212
Taylor DAH (1974) 13C Nuclear Magnetic Resonance spectra of some limonoids. Part-1. The structure of Procerin, an extractive from Carapa procera. J Chem Soc Pt 1:437–441
Titanji VPK, Evehe MS, Ayafor JF, Kimbu SF (1990) Novel Onchocerca volvulus filaricides from Carapa procera, Polyalthia suaveolens and Pachypodanthium staudtii. Acta Leidensia 59:377–382
Uddin SJ, Nahar L, Shilpi JA, Shoeb M, Borkowski T, Gibbons S, Middleton M, Byres M, Sarker SD (2007) Gedunin a Limonoid from Xylocarpus granatum, Inhibits the Growth of CaCo-2 Colon Cancer Cell Line In Vitro. Phytother Res 21:757–761
Wu J, Xiao Q, Zhang S, Li X, Xiao Z, Ding H, Lia Q (2005) Xyloccensins Q-V, six new 8,9,30-phragmalin ortho ester antifeedants from the Chinese mangrove Xylocarpus granatum. Tetrahedron 61:8382–8389
Yin S, Wang X-N, Fan C-Q, Lin L-P, Ding J, Yue J-M (2007) Limonoids from the seeds of the marine mangrove Xylocarpus granatum. J Nat Prod 70(4):682–685
Yusuf M, Chowdhury JU, Wahab MA, Begum J (1994) Medicinal plants of Bangladesh. BCSIR Laboratories, Chittagong, Bangladesh p, 263
Zaridah MZ, Idid SZ, Wan-Omar A, Khozirah S (2001) In vitro antifilarial effects of three plant species against adult worms of sub periodic Brugia malayi. J Ethnopharmacol 78:79–84
Acknowledgements
The study was supported by Department of Ocean Development, New Delhi, India. We thank Mr. A. K. Roy and Mr. R. N. Lal for providing technical assistance. The financial assistance in the form of fellowship to S.M. by Council of Scientific and Industrial Research, New Delhi, India and to M.V. by World Health Organization, Geneva under CDRI-WHO collaborative project (A70112) is gratefully acknowledged. This manuscript bears CDRI communication number 8034.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Misra, S., Verma, M., Mishra, S.K. et al. Gedunin and photogedunin of Xylocarpus granatum possess antifilarial activity against human lymphatic filarial parasite Brugia malayi in experimental rodent host. Parasitol Res 109, 1351–1360 (2011). https://doi.org/10.1007/s00436-011-2380-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-011-2380-x