Berberine is a potent agonist of peroxisome proliferator activated receptor alpha.
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.
Department of Pharmacology, Chongqing Medical University, Chongqing, China and Research Center of Neuroscience, Chongqing Medical University, Chongqing, China.
Huarong
H
Yu
Department of Pharmacology, Chongqing Medical University, Chongqing, China.
Changqing
C
Li
Department of Pharmacology, Chongqing Medical University, Chongqing, China.
Junqing
J
Yang
Department of Pharmacology, Chongqing Medical University, Chongqing, China.
Tao
T
Zhang
Department of Pharmacology, Chongqing Medical University, Chongqing, China, 1426374720@qq.com.
Qixin
Q
Zhou
D000818:Animals; D001599:Berberine / Q000493:pharmacokinetics / Q000494:pharmacology*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D000960:Hypolipidemic Agents; D047493:PPAR alpha; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D001599:Berberine; D002334:Carnitine O-Palmitoyltransferase; C583748:carnitine palmitoyltransferase-1a, rat