title: Triterpenes from Alisma orientalis act as androgen receptor agonists, progesterone receptor antagonists, and glucocorticoid receptor antagonists.
abstract: Alisma orientalis, a well-known traditional medicine, exerts numerous pharmacological effects including anti-diabetes, anti-hepatitis, and anti-diuretics but its bioactivity is not fully clear. Androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) are three members of nuclear receptor superfamily that has been widely targeted for developing treatments for essential diseases including prostate cancer and breast cancer. In this study, two triterpenes, alisol M 23-acetate and alisol A 23-acetate from Alisma orientalis were determined whether they may act as androgen receptor (AR), progesterone receptor (PR), or glucocorticoid receptor (GR) modulators. Indeed, in the transient transfection reporter assays, alisol M 23-acetate and alisol A 23-acetate transactivated AR in dose-dependent manner, while they transrepressed the transactivation effects exerted by agonist-activated PR and GR. Through molecular modeling docking studies, they were shown to respectively interact with AR, PR, or GR ligand binding pocket fairly well. All these results indicate that alisol M 23-acetate and alisol A 23-acetate from Alisma orientalis might possess therapeutic effects through their modulation of AR, PR, and GR pathways.
authors.affiliation: Department of Chemistry, College of Science, National Kaohsiung Normal University, No. 62, Shenjhong Rd., Yanchao District, Kaohsiung City 82446, Taiwan, Republic of China. Electronic address: t3136@nknucc.nknu.edu.tw.
authors.forename: Hsiang-Ru
authors.initials: HR
authors.lastname: Lin
mesh_terms: D034902:Alisma / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011944:Receptors, Androgen / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D014315:Triterpenes
keywords: Alisol A 23-acetate; Alisol M 23-acetate; Androgen receptor; Glucocorticoid receptor; Natural product; Nuclear receptor; Progesterone receptor