Abstract
ObjectiveTo explore the mechanistic effects of Yajieshaba (YJSB) on enhanced liver detoxification. MethodsThe effects of YJSB on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed in five acute chemical liver injury models [carbon tetrachloride (CCl4), D-galactosamine (D-Glan), 4-acetamidophenol (AAP), thioacetamide (TAA) and 1-naphthyl isothiocyanate (ANIT)]. Sleep latency and sleep time of pentobarbital sodium were tested in control mice and CCl4 model miceafter oral YJSB administration. The effects of YJSB on drug metabolism enzymes of liver microsomes were tested in control rats and CCl4 model rats. The levels of cytochrome P450 (CYP450) and Cyt b5 in liver microsomes were assayed using the method by Omura and Sato, and activities of erythromycin N-demethylase (ERD) and aminopyrine N-demethyl (ADM) were evaluated by Nash colorimetry. Probe substrate-based high performance liquid chromatography (HPLC) methods were established for CYP3A4 and CYP1A2. ResultsThe level of serum ALT was reduced by YJSB at 3.51 g/kg in the five models as follows: CCl4 > D-Glan, AAP, ANIT > TAA. YJSB treatment did not reduce the level of serum AST. YJSB at 3.51 g/kg prolonged the sleep latency in control mice and shortened the sleep time of control mice and CCl4 model mice. For control rats, YJSB at 2.43 g/kg increased the levels of CYP450 and Cyt b5 and induced the activities of ERD and ADM; for liver injuries induced by CCl4 in rats, YJSB at 2.43 g/kg increasedthe levels of CYP450 and Cyt b5. These results suggest that YJSB at 2.43 g/kg induces CYP3A4 and CYP1A2. ConclusionThese results suggest that YJSB enhanced liver detoxification and the mechanisms may be partially related to CYP3A4 and CYP1A2 induction.
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