Triterpenes from Alisma orientalis act as farnesoid X receptor agonists.
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.
Department of Chemistry, College of Science, National Kaohsiung Normal University, No. 62, Shenjhong Rd., Yanchao District, Kaohsiung City 82446, Taiwan, ROC. t3136@nknucc.nknu.edu.tw
Hsiang-Ru
HR
Lin
D034902:Alisma / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D014315:Triterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000099150:Receptor, Farnesoid X-Activated
D018160:Receptors, Cytoplasmic and Nuclear; D014315:Triterpenes; D000099150:Receptor, Farnesoid X-Activated