title: Geniposide Suppresses Hepatic Glucose Production via AMPK in HepG2 Cells.
abstract: Geniposide is one of the main compounds in Gardenia jasminoides ELLIS and has many pharmacological activities, but its anti-hyperglycemic activity has not yet been fully explored. This study was designed to determine, for the first time, how geniposide from G. jasminoides regulates hepatic glucose production, and the underlying mechanisms. During in vitro study, we found the inhibitory effect of geniposide on the hepatic glucose production is partly through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Geniposide significantly inhibited hepatic glucose production in a dose-dependent manner. AMPK, acetyl coenzyme A synthetase (ACC) and forkhead box class O1 (FoxO1) phosphorylation were stimulated by different concentrations of geniposide. In addition, the enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were all significantly suppressed. What is important is that these effects were partly reversed by (1) inhibition of AMPK activity by compound C, a selective AMPK inhibitor, and by (2) suppression of AMPKα expression by small interfering RNA (siRNA). In summary, geniposide potentially ameliorates hyperglycemia through inhibition of hepatic gluconeogenesis by modulation of the AMPK-FoxO1 signaling pathway. Geniposide or geniposide-containing medicinal plants could represent a promising therapeutic agent to prevent type 2 diabetes on gluconeogenesis.
authors.affiliation: Chongqing Key Lab of Catalysis & Functional Organic Molecules, Chongqing Technology and Business University.
authors.forename: Lixia
authors.initials: L
authors.lastname: Guo
authors.forename: Xuxu
authors.initials: X
authors.lastname: Zheng
authors.forename: Jianhui
authors.initials: J
authors.lastname: Liu
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Yin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D000071161:Forkhead Box Protein O1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D039823:Iridoids / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D007004:Hypoglycemic Agents; D039823:Iridoids; D034741:RNA, Small Interfering; C007835:geniposide; D055372:AMP-Activated Protein Kinases; D005947:Glucose