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Clinical Trial
. 2004 Dec;10(12):1344-51.
doi: 10.1038/nm1135. Epub 2004 Nov 7.

Berberine Is a Novel Cholesterol-Lowering Drug Working Through a Unique Mechanism Distinct From Statins

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Clinical Trial

Berberine Is a Novel Cholesterol-Lowering Drug Working Through a Unique Mechanism Distinct From Statins

Weijia Kong et al. Nat Med. .

Abstract

We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients for 3 months reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. Treatment of hyperlipidemic hamsters with BBR reduced serum cholesterol by 40% and LDL-cholesterol by 42%, with a 3.5-fold increase in hepatic LDLR mRNA and a 2.6-fold increase in hepatic LDLR protein. Using human hepatoma cells, we show that BBR upregulates LDLR expression independent of sterol regulatory element binding proteins, but dependent on ERK activation. BBR elevates LDLR expression through a post-transcriptional mechanism that stabilizes the mRNA. Using a heterologous system with luciferase as a reporter, we further identify the 5' proximal section of the LDLR mRNA 3' untranslated region responsible for the regulatory effect of BBR. These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs.

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