title: Saponins from Platycodon grandiflorum inhibit hepatic lipogenesis through induction of SIRT1 and activation of AMP-activated protein kinase in high-glucose-induced HepG2 cells.
abstract: Saponins from the roots of Platycodon grandiflorum (Changkil saponins, CKS) have antioxidant and hepatoprotective properties. This study investigated the effects of CKS on AMP-activated protein kinase (AMPK) activation and hepatic lipogenesis in HepG2 cells. CKS suppressed high-glucose-induced lipid accumulation and inhibited high-glucose-induced fatty acid synthase (FAS) and sterol regulatory element binding protein-1c (SREBP-1c) expression in HepG2 cells. Moreover, the use of a pharmacological AMPK inhibitor revealed that AMPK is essential for the suppression of SREBP-1c expression in CKS-treated cells. Finally, the activation of calcium/calmodulin-dependent kinase kinase β (CaMKKβ) and SIRT1 was necessary for CKS-enhanced activation of AMPK. These results indicate that CKS prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through SIRT1 and CaMKKβ/AMPK activation. Using CKS to target AMPK activation may provide a promising approach for the prevention lipogenesis.
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Hwang
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.forename: Hyun-Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Chung
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D031238:Platycodon / Q000737:chemistry*; D012503:Saponins / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C491901:FAS protein, human; D010936:Plant Extracts; D012503:Saponins; D019014:fas Receptor; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005947:Glucose