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Chem Biol Interact. 2018 Oct 1;294:151-157. doi: 10.1016/j.cbi.2018.08.025. Epub 2018 Aug 24.

Deoxypodophyllotoxin in Anthriscus sylvestris alleviates fat accumulation in the liver via AMP-activated protein kinase, impeding SREBP-1c signal.

Author information

1
Korean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu, 41062, South Korea.
2
Medical Research Center, Daegu Haany University, Gyeongsan, 38610, South Korea.
3
Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06510, USA.
4
Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, 50612, South Korea.
5
Department of Biomedical Laboratory Science, Daekyeung College, Gyeongsan, 38547, South Korea.
6
Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, 50612, South Korea. Electronic address: ahnsc@pusan.ac.kr.
7
Medical Research Center, Daegu Haany University, Gyeongsan, 38610, South Korea. Electronic address: ywkim@dhu.ac.kr.

Abstract

Deoxypodophyllotoxin (DPT) is a naturally occurring flavolignan in Anthriscus sylvestris known as cow parsley or wild chervil, and has been reported to have inhibitory effects against several pathological processes including cancer, inflammation and infection. Here, we report the effects of DPT in the fatty liver induced by high fat diet in vivo as well as its regulatory mechanism related with the transcription factor for lipogenic genes such as sterol regulatory element binding protein-1c (SREBP-1c) in vitro. C57BL/6 mice were fed high fat diet for 10 weeks and also orally administrated with DPT for additional 4 weeks. 5 and 10 mg/kg of DPT decreased lipid accumulation in the liver induced by high fat diet, as indicated by histological parameters such as Oil Red O staining and hematoxylin & eosin as well as the contents of hepatic triglyceride and cholesterol. In hepatocytes, DPT inhibited the liver X receptor α-mediated SREBP-1c induction and expression of the lipogenic genes, including fatty acid synthase, acetyl-CoA carboxylase and stearoyl-CoA desaturase-1. Moreover, DPT induced AMP-activated protein kinase (AMPK) activation, which has been known to inhibit the expression of SREBP-1c in hepatocyte. Also this compound restored the dysregulation of AMPK and SREBP-1c induced by high fat diet in mice. In conclusion, we demonstrated that DPT significantly inhibited fatty liver by adjusting lipid metabolism coordinated with AMPK activation and SREBP-1c inhibition.

KEYWORDS:

AMPK; Deoxypodophyllotoxin; Hepatic steatosis; High fat diet; SREBP-1c

PMID:
30148990
DOI:
10.1016/j.cbi.2018.08.025
[Indexed for MEDLINE]

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