Abstract
Aim:
To discover the active compound on AMP-activated protein kinase (AMPK) activation and investigate the effects of the active compound 1,8-dihydroxyanthraquinone (danthron) from the traditional Chinese medicine rhubarb on AMPK-mediated lipid and glucose metabolism in vitro.
Methods:
HepG2 and C2C12 cells were used. Cell viability was determined using MTT assay. Real-time PCR was performed to measure the gene expression. Western blotting assay was applied to investigate the protein phosphorylation level. Enzymatic assay kits were used to detect the total cholesterol (TC), triglyceride (TG) and glucose contents.
Results:
Danthron (0.1, 1, and 10 μmol/L) dose-dependently promoted the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) in both HepG2 and C2C12 cells. Meanwhile, danthron treatment significantly reduced the lipid synthesis related sterol regulatory element-binding protein 1c (SREBP1c) and fatty acid synthetase (FAS) gene expressions, and the TC and TG levels. In addition, danthron treatment efficiently increased glucose consumption. The actions of danthron on lipid and glucose metabolism were abolished or reversed by co-treatment with the AMPK inhibitor compound C.
Conclusion:
Danthron effectively reduces intracellular lipid contents and enhanced glucose consumption in vitro via activation of AMPK signaling pathway.
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Acknowledgements
This work was supported by the National Science and Technology Major Project (grants 2012ZX09301001-004 and 2012ZX09103101-18), the National Natural Science Foundation of China (grants 81173105 and 91213306), the Foundation of Chinese Academy of Sciences (grant KSCX2-EW-Q-3), the National Marine 863 Programme (grant 2011AA09070102) and the Science Foundation of Shanghai (grant 11XD1406100).
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Zhou, R., Wang, L., Xu, X. et al. Danthron activates AMP-activated protein kinase and regulates lipid and glucose metabolism in vitro. Acta Pharmacol Sin 34, 1061–1069 (2013). https://doi.org/10.1038/aps.2013.39
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DOI: https://doi.org/10.1038/aps.2013.39
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