title: Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells.
abstract: AMP-activated protein kinase (AMPK) plays a central role in controlling hepatic lipid metabolism through modulating the downstream acetyl CoA carboxylase (ACC) and sterol regulatory element-binding protein-1c (SREBP-1c) pathway. Saponins, particularly platycodin D, from the roots of Platycodon grandiflorum (Changkil saponins, CKS) have a variety of pharmacological properties, including antioxidant and hepatoprotective properties. The aim of this study was to investigate the effects of CKS on hepatic lipogenesis and on the expression of genes involved in lipogenesis, and the mechanisms involved. CKS attenuated fat accumulation and the induction of the lipogenic genes encoding SREBP-1c and fatty acid synthase in the livers of HFD-fed rats and in steatotic HepG2 cells. Blood biochemical analyses and histopathological examinations showed that CKS prevented liver injury. CKS and platycodin D each increased the phosphorylation of AMPK and acetyl-CoA carboxylase in HFD-fed rats and HepG2 cells. The use of specific inhibitors showed that platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells. This study demonstrates that CKS or platycodin D alone can regulate hepatic lipogenesis via an AMPK-dependent signalling pathway.
authors: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Yong Pil
authors: YP
authors: Hwang
authors: Jae Ho
authors: JH
authors: Choi
authors: Hyung Gyun
authors: HG
authors: Kim
authors: Tilak
authors: T
authors: Khanal
authors: Gye Young
authors: GY
authors: Song
authors: Myoung Soo
authors: MS
authors: Nam
authors: Hyun-Sun
authors: HS
authors: Lee
authors: Young Chul
authors: YC
authors: Chung
authors: Young Chun
authors: YC
authors: Lee
authors: Hye Gwang
authors: HG
authors: Jeong
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000502:physiology; D059305:Diet, High-Fat; D064429:Fatty Acid Synthases / Q000235:genetics; D005947:Glucose / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D031238:Platycodon / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D012503:Saponins; D051780:Sterol Regulatory Element Binding Protein 1; D014315:Triterpenes; C108953:platycodin D; D064429:Fatty Acid Synthases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005947:Glucose