Pharmacological properties of dibenzo[a,c]cyclooctene derivatives isolated from Fructus Schizandrae chinensis. I. Interaction with rat liver cytochrome P-450 and inhibition of xenobiotic metabolism and mutagenicity.
Seven compounds isolated from Fructus Schizandrae chinensis, a traditional Chinese tonic, which is also able to increase liver lesions by hepatoxic chemicals, are named Schizandrin (Sin) A, B and C, Schizandrol (Sol) A and B and Schizandrer (Ser) A and B. They are dibenzo[a,c]cyclooctene derivatives. Dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxy-biphenyl-2,2'-dicarboxylate (DDB) is an intermediate for synthesizing Sin C. The interactions of these compounds with rat liver microsomes in vitro have been investigated. Sol A and Sol B gave type I difference spectrum, the other six compounds gave 'reverse type I' difference spectrum. When Schizandrins or DDB were incubated with NADPH-reduced microsomes, Sin B, Sin C, Sol B, Ser A and Ser B generated dual Soret peaks of 455--460 nm and 425--430 nm, the other three compounds caused a difference spectrum without 455 nm peak. All these compounds more or less inhibit liver microsomal hydroxylation of benzo[a]pyrene (BP) demethylation of aminopyrine. Sin B, Sol B and DDB decreased mutagenicity of BP in Ames test.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D034242:Cyclooctanes; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004149:Dioxoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D008516:Medicine, Chinese Traditional; D008518:Medicine, East Asian Traditional; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010946:Plants, Medicinal; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; D009153:Mutagens; D011083:Polycyclic Compounds; C015499:schizandrin B; D009249:NADP; C033585:schizandrol B; C082090:schisantherin B; C034734:schizandrin A; C034557:schizandrer A; D003577:Cytochrome P-450 Enzyme System; C031409:schizandrin C; D001189:Aryl Hydrocarbon Hydroxylases; C011105:schizandrin