title: Sesquiterpenoids from Atractylodes macrocephala act as farnesoid X receptor and progesterone receptor modulators.
abstract: Two sesquiterpenoids, atractylenolide II and III, were isolated and identified from Atractylodes macrocephala (Asteraceae) to be subsequently evaluated for their activity against farnesoid X receptor (FXR) and progesterone receptor (PR) by transient transfection reporter assays. These sesquiterpenoids did not exert significant agonistic effect but antagonized the activity of chenodeoxycholic acid (CDCA), an endogenous FXR agonist, for FXR driven SHP promoter transactivation. Additionally, they transactivated CYP7A1 gene promoter activity by antagonizing FXR. Apart from acting as a FXR antagonist, atractylenolide III also showed agonistic activity against PR. All these results demonstrated that atractylenolide II and III are the active components of Atractylodes macrocephala to exert specific pharmacologic effects.
authors.affiliation: Department of Chemistry, College of Science, National Kaohsiung Normal University, Yanchao District, Kaohsiung City, Taiwan, ROC.
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Tsai
authors.forename: Jui-Wei
authors.initials: JW
authors.lastname: Liang
authors.forename: Hsiang-Ru
authors.initials: HR
authors.lastname: Lin
mesh_terms: D031174:Atractylodes / Q000737:chemistry*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D006470:Hemorrhage / Q000188:drug therapy / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D010936:Plant Extracts / Q000737:chemistry; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D015533:Transcriptional Activation; D014162:Transfection; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D002790:Cholesterol 7-alpha-Hydroxylase; D000960:Hypolipidemic Agents; D008156:Luciferases; D010936:Plant Extracts; D018160:Receptors, Cytoplasmic and Nuclear; D011980:Receptors, Progesterone; D012717:Sesquiterpenes; D000099150:Receptor, Farnesoid X-Activated; C553219:CYP7A1 protein, human