title: Diarylheptanoid compounds from Alnus nepalensis express in vitro and in vivo antifilarial activity.
abstract: A large number of medicinal plants remain to be explored for antifilarial compounds. In the present study a crude methanolic extract of leaves of Alnus nepalensis, chloroform- and n-butanol-partitioned fractions from the crude extract and 6 bioactivity-guided isolated compounds including two new diarylheptanoid from the fractions were assayed for microfilaricidal, macrofilaricidal and female worm sterilizing activity using the lymphatic filariid Brugia malayi in in vitro and in vivo systems. In vitro, the crude methanolic extract exerted better microfilaricidal (LC100: 15.63μg/ml, IC50: 6.00μg/ml) than macrofilaricidal (LC100: >250; IC50: 88μg/ml) activity whereas chloroform and n-butanol fractions were more macrofilaricidal (LC100: 125 and 31.25μg/ml; IC50: 13.14 and 11.84, respectively) than microfilaricidal (LC100: 250-500μg/ml, IC50: 44.16μg/ml). In addition, n-butanol fraction also caused 74% inhibition in MTT reduction potential of the adult worms. In vivo (doses: crude: 100-200mg/kg; fractions: 100mg/kg, i.p.×5 days) the chloroform fraction exerted >50% macrofilaricidal activity whereas methanolic extract and n-butanol fraction produced 38-40% macrofilaricidal action along with some female sterilizing efficacy. Of the 5 diarylheptanoid compounds isolated, alnus dimer, and (5S)-5-hydroxy-1-(4-hydroxyphenyl)-7-(3,4-dihydroxyphenyl)-3-heptanone were found to show the most potent with both macrofilaricidal (LC100: 15.63μg/ml, IC50: 6.57-10.31μg/ml) and microfilaricidal (LC100: 31.25-62.5μg/ml, IC50: 11.05-22.10μg/ml) activity in vitro. These findings indicate that the active diarylheptanoid compounds may provide valuable lead for design and development of new antifilarial agent(s).
authors.affiliation: Analytical Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Yadav
authors.forename: Vikas
authors.initials: V
authors.lastname: Kushwaha
authors.forename: Kirti
authors.initials: K
authors.lastname: Saxena
authors.forename: Richa
authors.initials: R
authors.lastname: Verma
authors.forename: P Kalpana
authors.initials: PK
authors.lastname: Murthy
authors.forename: Madan M
authors.initials: MM
authors.lastname: Gupta
mesh_terms: D029661:Alnus / Q000737:chemistry*; D000818:Animals; D017178:Brugia malayi / Q000187:drug effects*; D036381:Diarylheptanoids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005368:Filariasis / Q000188:drug therapy / Q000469:parasitology; D005369:Filaricides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D005849:Gerbillinae; D020128:Inhibitory Concentration 50; D008297:Male; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D036381:Diarylheptanoids; D005369:Filaricides; D010936:Plant Extracts
keywords: Alnus nepalensis; Anti-filarial; Diarylheptanoids