The research of the hepatotoxicity of polygonum multiflorum on the basic of the inhibition of the UGT1A1 enzyme in vivo and in vitro / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the hepatotoxicity of Polygonum multiflorum on the basic of the bilirubin metabolism mediated by glucuronidation of UGT1A1 enzyme. METHODS: Inspected the enzyme kinetic parameters after giving the rats Polygonum multiflorum extract orally(in vivo), and added the Polygonum multiflorum extract into the human liver microsome(rat liver microsome; human recombinant UGT1A1 enzyme) to test the hepatotoxicity using the bilirubin as UGT1A1 enzyme substrate, investigating the inhibition of the UGT1A1 enzyme(in vitro). Apparent inhibition constant Ki and enzyme kinetic parameters were used to evaluate the hepatotoxicity. RESULTS: Polygonum multiflorum extract has a strong inhibiton to the UGT1A1 enzyme in all the three systems in vitro. All the type of inhibition is the competitive inhibition. While Polygonum multiflorum extract has a strong inhibiton to the UGT1A1 enzyme in vivo, but the type of inhibition is the uncompetitive inhibition. CONCLUSION: The method we had established in our study provides a new idea and a new method to evaluate the hepatotoxicity and the safety of Chinese herbs.