Planta Med 2010; 76 - P346
DOI: 10.1055/s-0030-1264644

In vitro hepatic biotransformation of cepharanthine, a bisbenzylisoquinoline alkaloid

S Bory 1, S Koeut 1, S Bun 1, B Baghdikian 1, R Elias 1, H Bun 2, E Ollivier 1
  • 1Faculty of Pharmacy, Laboratory of Pharmacognosy and Ethnopharmacology, UMR-MD3, 27 Bd Jean Moulin, 13385 Marseille cedex 5, France
  • 2Faculty of Pharmacy, Laboratory of Toxicokinetics and Pharmacokinetics, UMR-MD3, 27 bd Jean Moulin, 13385 cedex 5 Marseille, France

Cepharanthine is a major biscoclaurine (bisbenzylisoquinoline) alkaloid isolated from the tuber of Stephania rotunda Lour., a Cambodian creeper belonging to the family of Menispermaceae [1]. Cepharanthine exerts various biological effects including antiplasmodial [1], cytotoxic [2] and antioxidant [3] activies, but the metabolism of this compound has not been elucidated to date. The aim of the present investigation was to study in vitro phase I metabolism of cepharanthine using liver microsomes from different species. Incubation of cepharanthine with human liver microsomes led to the formation of one major metabolite, detected by HPLC-DAD. Enzyme kinetics were investigated with pooled human liver microsomes. The apparent Michaelis-Menten constants for the human major metabolite were Km=37.7µM and Vm=22.7 nmol/mg/h. We conducted inter-individual variability study using 20 different human liver microsomes. Results showed marked inter-individual differences in human cepharanthine metabolism. In addition, the biotransformation of this alkaloid was investigated using liver microsomes from different animal species (rats, mice, rabbits, guinea-pigs). Experiments showed important inter-species variability of cepharanthine metabolism


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3. Gülçin, I. et al. (2010)J. Enzyme Inhib. Med. Chem. 25:44–53.