IMR Press / FBL / Volume 21 / Issue 5 / DOI: 10.2741/4440

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Berberine is a potent agonist of peroxisome proliferator activated receptor alpha

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1 Department of Pharmacology, Chongqing Medical University, Chongqing, China
2 Research Center of Neuroscience, Chongqing Medical University, Chongqing, China
Academic Editor:Zhongjie Sun
Front. Biosci. (Landmark Ed) 2016, 21(5), 1052–1060; https://doi.org/10.2741/4440
Published: 1 June 2016
(This article belongs to the Special Issue Molecular basis of metabolic syndrome in cardiovascular disease)
Abstract

Although berberine has hypolipidemic effects with a high affinity to nuclear proteins, the underlying molecular mechanism for this effect remains unclear. Here, we determine whether berberine is an agonist of peroxisome proliferator-activated receptor alpha (PPARalpha), with a lipid-lowering effect. The cell-based reporter gene analysis showed that berberine selectively activates PPARalpha (EC50 =0.58 mM, Emax =102.4). The radioligand binding assay shows that berberine binds directly to the ligand-binding domain of PPARalpha (Ki=0.73 mM) with similar affinity to fenofibrate. The mRNA and protein levels of CPT-Ialpha gene from HepG2 cells and hyperlipidemic rat liver are remarkably up-regulated by berberine, and this effect can be blocked by MK886, a non-competitive antagonist of PPARalpha. A comparison assay in which berberine and fenofibrate were used to treat hyperlipidaemic rats for three months shows that these drugs produce similar lipid-lowering effects, except that berberine increases high-density lipoprotein cholesterol more effectively than fenofibrate. These findings provide the first evidence that berberine is a potent agonist of PPARalpha and seems to be superior to fenofibrate for treating hyperlipidemia.

Keywords
Berberine
hPPARalpha
Agonist
CPT-Ialpha
Fenofibrate
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