Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 58, Issue 11, Pages 2133-2145Publisher
WILEY-BLACKWELL
DOI: 10.1002/mnfr.201400366
Keywords
Curcumin; HNF-1 alpha; Hypercholesterolemia; LDLR; PCSK9
Categories
Funding
- National Science Council [NSC-102-2313-B-320-001-MY3, NSC-102-2320-B-041-003-MY3]
- Buddhist Tzu Chi General Hospital, Taiwan [TCRD-103-17]
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Scope: Curcumin has been demonstrated as having numerous desirable characteristics, such as antioxidant, anti-inflammatory, and antiatherogenic activities. We report the hypocholesterolemic effect and molecular mechanism of curcumin. Methods and results: We found that curcumin enhanced LDL receptor (LDLR) level on the cell surface, as well as LDLR activity; however, LDLR transcription and mRNA stability were not affected. Furthermore, we found that proprotein convertase subtilisin/kexin type 9 (PCSK9) gene was downregulated at the transcriptional level by curcumin, leading to an increase in LDL uptake in HepG2 cells. The curcumin-responsive element of the PCSK9 promoter, a binding site for hepatocyte nuclear factor 1 alpha (HNF-1 alpha), was also identified. We demonstrated that curcumin reduced the nuclear abundance of hepatocyte nuclear factor 1 alpha, resulting in its attenuated interaction with the PCSK9 promoter and leading to a downregulation of PCSK9 expression. Finally, we showed that curcumin decreased the statin-induced PCSK9 expression and potentially synergized with statin administration. Conclusion: Current results indicate that curcumin suppression of PCSK9 expression is associated with increases in cell-surface LDLR and LDLR activity in hepatic cells and it acts in a molecular mechanism that is distinct from the statins. Curcumin exhibits hypolipidemic activity and may serve as a useful supplement to statin treatment for hypercholesterolemia.
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