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01-01-2020 | Fatty Liver | Original Paper

Cynandione A from Cynanchum wilfordii inhibits hepatic de novo lipogenesis by activating the LKB1/AMPK pathway in HepG2 cells

Authors: Sunggun Kim, Yeo Yeong Yoon, Ye Won Park, Wan-Kyunn Whang, So-Young Park, Kwang Woo Hwang

Published in: Journal of Natural Medicines | Issue 1/2020

Abstract

Cynandione A (CA), isolated from ethyl acetate extract of Cynanchum wilfordii (CW), is a bioactive phytochemical that has been found to be beneficial for the treatment of several diseases. Hepatic de novo lipogenesis is one of the main causes of non-alcoholic fatty liver disease (NAFLD), which is thought to be a hepatic manifestation of certain metabolic syndromes. However, it has not yet been reported if CA has any therapeutic value in these diseases. Here, we investigated whether CA can inhibit hepatic lipogenesis induced by liver X receptor α (LXRα) using an in vitro model. We found that the extract and ethyl acetated layer of CW decreased the mRNA levels of sterol regulatory element-binding protein-1c (SREBP-1c), which plays a crucial role in hepatic lipogenesis. Additionally, we observed that CA could suppress the level of SREBP-1c, which was increased using two commercial LXRα agonists, GW3954 and T0901317. Moreover, the enzymes that act downstream of SREBP-1c were also inhibited by CA treatment. To understand the mechanism underlying this effect, the levels of phosphorylated AMP kinase (pAMPK) were measured after CA treatment. Therefore, CA might increase the pAMPK level by inducing phosphorylation of liver kinase B1 (LKB1), which can then convert AMPK to pAMPK. Taken together, we conclude that CA has an alleviative effect on hepatic lipogenesis through the stimulation of the LKB1/AMPK pathway.

Graphical abstract

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Title: Cynandione A from Cynanchum wilfordii inhibits hepatic de novo lipogenesis by activating the LKB1/AMPK pathway in HepG2 cells
Authors: Sunggun Kim
Yeo Yeong Yoon
Ye Won Park
Wan-Kyunn Whang
So-Young Park
Kwang Woo Hwang
Publication date: 01-01-2020
Publisher: Springer Singapore
Keyword: Fatty Liver
Published in: Journal of Natural Medicines / Issue 1/2020
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-019-01356-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Cynandione A from Cynanchum wilfordii inhibits hepatic de novo lipogenesis by activating the LKB1/AMPK pathway in HepG2 cells

Abstract

Graphical abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Graphical abstract

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