Triterpenes from Alisma orientalis act as farnesoid X receptor agonists

Abstract

Alisma orientalis is a well-known traditional medicine exerting pharmacological effects including antidiabetes, antihepatitis, and antidiuretics, but the respective molecular mechanism is not completely clear. Farnesoid X receptor (FXR) is a member of nuclear receptor superfamily and viewed as one of the essential target proteins to develop antidiabetic treatments. In this study, the triterpenes, alisol M 23-acetate and alisol A 23-acetate, were isolated from A. orientalis and further evaluated for their activity against FXR. In the mammalian one-hybrid and transient transfection reporter assays, both triterpenes transactivated FXR to modulate promoter action including GAL4, SHP, CYP7A1, and PLTP promoters in dose-dependent manner, while they exhibited similar agonistic activity as chenodeoxycholic acid (CDCA), an endogenous FXR agonist. These results highly indicated that alisol M 23-acetate and alisol A 23-acetate acted as FXR agonists so A. orientalis might exert therapeutic effect including antihyperglycemic effect through FXR pathway.