Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins.
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.
Kong
Weijia
W
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, 100050, China.
Wei
Jing
J
Abidi
Parveen
P
Lin
Meihong
M
Inaba
Satoru
S
Li
Cong
C
Wang
Yanling
Y
Wang
Zizheng
Z
Si
Shuyi
S
Pan
Huaining
H
Wang
Shukui
S
Wu
Jingdan
J
Wang
Yue
Y
Li
Zhuorong
Z
Liu
Jingwen
J
Jiang
Jian-Dong
JD
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001599:Berberine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015152:Blotting, Northern; D002681:China; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D006224:Cricetinae; D017931:DNA Primers; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008099:Liver / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood; D014407:Tumor Cells, Cultured
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D017931:DNA Primers; D011973:Receptors, LDL; D014280:Triglycerides; D001599:Berberine; D002784:Cholesterol