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.