Biol. Pharm. Bull. 30(9) 1702—1706 (2007)

has been prescribed to improve health and longevity in the traditional Chinese medicine, and it was used for the treatment of neurasthenia, hypertension, hepatopathy and carcinoma for thousands of years. More than one hundred species of bioactive components have been isolated from G. lucidum, such as polysaccharides, triterpenoids and alkaloids, in which that Ganoderma lucidum polysaccharide (GLPS) is one of the major active components. Its multiple pharmacological effects, such as antitumor, antioxidation, immunomodulation and especially hepatoprotection against chemical or immune hepatic damage, have been demonstrated in many animal models in vivo and in vitro. However, the accurate protective mechanism of GLPS on the liver damage is still unknown. Cytochrome P450 (P450) monooxygenase superfamily is the most important phase I metabolic enzyme system in liver. P450 is not only responsible for the oxidative metabolism of numerous exogenous compounds and endogenous hormones, but also plays a critical role involving in the activation of various chemical toxicant and procarcinogen. There are researches which have confirmed that the expressions and activities of some P450 isoenzymes may be down-regulated under the inflammatory or infecting condition, and then resulting in change of the metabolic capability of the enzymes. However, whether P450 down-regulation is a homeostatic mechanism or a pathophysiological phenomenon has not been elucidated. On the other hand, because G. lucidum is currently popularly used as self-medication in East Asia, thus, it is needed to be investigated that whether GLPS influences P450 metabolic activity. Bacillus Calmette Guérin (BCG), a live attenuated Mycobacterium bovis, is clinically used as a preventing vaccine for tuberculosis or therapeutic regimens for bladder cancer. On the other hand, some cases of disseminated BCG infection have been proven to induce granulomatous hepatitis, sepsis and multiple organ failure in these patients. Several animal experiments have confirmed that BCG infection could induce the immune hepatic injury and production of inflammatory cytokines, active free radicals and nitric oxide (NO). Moreover, it was reported that microsomal P450 content and activity were suppressed by NO from inducible nitric oxide synthase (iNOS) during BCG infection in rodent liver. Therefore, the pharmacokinetics of P450 metabolized substrates may be changed by BCG in clinical patients, leading to enhancement of the therapeutic or adverse effects of drugs. In our previous experiment, it has been observed that GLPS inhibits iNOS expression or NO production, and mitigates immune liver injury induced by BCG in mice in vivo and in vitro. The purpose of the present study was to investigate the effect of GLPS on the metabolic activities of three P450 isoenzymes including CYP2E1, CYP1A2 and CYP3A, which are abundantly expressed in liver, and further to evaluate whether GLPS modulating P450 activity involved in the hepatoprotective mechanism under the similar damaged condition with our previous study in rats.