Shosaikoto (a Kampo medicine) modulates changes in cytochrome P450 caused by Mycobacteriumbutyricum injection

A large number of infectious or inflammatory agents are well known to reduce cytochrome P450-catalyzed drug metabolism in the liver. Changes in the levels of hepatic P450s in infectious or inflammatory diseases can lead to alteration in physiology, therapeutic failure, and disease development. This study was therefore designed to examine the effect of shosaikoto, a Kampo medicine used for treatment of chronic hepatitis and acute flu, on the changes in P450 activity and protein levels following intravenous injection of Mycobacterium butyricum. Intravenous injection of M. butyricum into rats reduced hepatic P450: CYP1A1, 1A2, 2B, and 3A activities and CYP2E1 and 3A2 protein levels. When administered orally to rats for 2 weeks since 1 week before M. butyricum injection, shosaikoto prevented the reduction in CYP1A1, 1A2, 2B, and 3A activities dose dependently and further abrogated the repression of CYP3A2 protein but not CYP2E1 protein. Serum C-reactive protein levels in this rat model were not highly elevated, and neither were significantly influenced by shosaikoto treatment. Taken together, these results suggest that shosaikoto would be capable of modulating the change in hepatic P450 caused by M. butyricum injection and the effect, which might not be brought about by its anti-inflammatory activity but by translational or posttranslational regulation, appears to differ in each P450 isoform.