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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. - Highlights: ► CKS attenuated fat accumulation in HFD-fed rats and in steatotic HepG2 cells. ► CKS and its major component, platycodin D, inhibited the levels ofmore » SREBP-1 and FAS. ► CKS and platycodin D increased the phosphorylation of AMPK and ACC. ► Platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells.« less

Authors:
 [1]; ; ; ;  [1];  [2];  [3]; ;  [4]
  1. Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764 (Korea, Republic of)
  2. College of Agriculture and Life Sciences, Chungnam National University, Daejeon (Korea, Republic of)
  3. Molecular Cancer Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of)
  4. Division of Food Science, International University of Korea, Jinju (Korea, Republic of)
Publication Date:
OSTI Identifier:
22285251
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 267; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMP; BLOOD; CARBOXYLASE; CARBOXYLIC ACIDS; DIET; FATS; GLUCOSE; LIVER; METABOLISM; PHOSPHORYLATION; RATS; SAPONINS; STEROLS

Citation Formats

Hwang, Yong Pil, Department of Pharmaceutical Engineering, International University of Korea, Jinju, Choi, Jae Ho, Kim, Hyung Gyun, Khanal, Tilak, Song, Gye Young, Nam, Myoung Soo, Lee, Hyun-Sun, Chung, Young Chul, Lee, Young Chun, and Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr. Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2013.01.001.
Hwang, Yong Pil, Department of Pharmaceutical Engineering, International University of Korea, Jinju, Choi, Jae Ho, Kim, Hyung Gyun, Khanal, Tilak, Song, Gye Young, Nam, Myoung Soo, Lee, Hyun-Sun, Chung, Young Chul, Lee, Young Chun, & Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr. Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells. United States. https://doi.org/10.1016/J.TAAP.2013.01.001
Hwang, Yong Pil, Department of Pharmaceutical Engineering, International University of Korea, Jinju, Choi, Jae Ho, Kim, Hyung Gyun, Khanal, Tilak, Song, Gye Young, Nam, Myoung Soo, Lee, Hyun-Sun, Chung, Young Chul, Lee, Young Chun, and Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr. 2013. "Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells". United States. https://doi.org/10.1016/J.TAAP.2013.01.001.
@article{osti_22285251,
title = {Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells},
author = {Hwang, Yong Pil and Department of Pharmaceutical Engineering, International University of Korea, Jinju and Choi, Jae Ho and Kim, Hyung Gyun and Khanal, Tilak and Song, Gye Young and Nam, Myoung Soo and Lee, Hyun-Sun and Chung, Young Chul and Lee, Young Chun and Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr},
abstractNote = {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. - Highlights: ► CKS attenuated fat accumulation in HFD-fed rats and in steatotic HepG2 cells. ► CKS and its major component, platycodin D, inhibited the levels of SREBP-1 and FAS. ► CKS and platycodin D increased the phosphorylation of AMPK and ACC. ► Platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells.},
doi = {10.1016/J.TAAP.2013.01.001},
url = {https://www.osti.gov/biblio/22285251}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 267,
place = {United States},
year = {Fri Mar 01 00:00:00 EST 2013},
month = {Fri Mar 01 00:00:00 EST 2013}
}