The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Cajanus cajan (L.) Millsp.) Leaves on Regulating LDLR and PCSK9 Expression in HepG2 Cells

Autor: Huei-Ru Lin, Chen-I Chen, Chen Pei-Yi, Ming-Jiuan Wu, Jia-Ru Wu, Jui-Hung Yen, Wan-Yun Gao, Heng-Yuan Chang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Pharmaceutical Science
HNF-1α
030204 cardiovascular system & hematology
Reductase
Cajanus cajan (L.) Millsp
Analytical Chemistry
PCSK9
Cajanus
chemistry.chemical_compound
0302 clinical medicine
Genes
Reporter
Drug Discovery
Promoter Regions
Genetic
0303 health sciences
biology
food and beverages
cajaninstilbene acid
Hep G2 Cells
Fatty acid synthase
medicine.anatomical_structure
Cholesterol
Biochemistry
Chemistry (miscellaneous)
Hepatocyte
Molecular Medicine
Kexin
lipids (amino acids
peptides
and proteins)
Proprotein Convertase 9
Transcriptional Activation
Article
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
medicine
Humans
RNA
Messenger
Physical and Theoretical Chemistry
030304 developmental biology
Plant Extracts
Lipogenesis
Organic Chemistry
Proprotein convertase
biology.organism_classification
Plant Leaves
LDLR
chemistry
Gene Expression Regulation
Receptors
LDL
LDL receptor
biology.protein
Biomarkers
Zdroj: Molecules
Volume 24
Issue 3
Molecules, Vol 24, Iss 3, p 493 (2019)
ISSN: 1420-3049
DOI: 10.3390/molecules24030493
Popis: Pigeon pea (Cajanus cajan (L.) Millsp.) is a legume crop consumed as an indigenous vegetable in the human diet and a traditional medicinal plant with therapeutic properties. The current study highlights the cholesterol-modulating effect and underlying mechanisms of the methanol extract of Cajanus cajan L. leaves (MECC) in HepG2 cells. We found that MECC increased the LDLR expression, the cell-surface LDLR levels and the LDL uptake activity in HepG2 cells. We further demonstrated that MECC suppressed the proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and protein expression, but not affected the expression of other cholesterol or lipid metabolism-related genes including inducible degrader of LDLR (IDOL), HMG-CoA reductase (HMGCR), fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC1), and liver X receptor-&alpha
(LXR-&alpha
) in HepG2 cells. Furthermore, we demonstrated that MECC down-regulated the PCSK9 gene expression through reducing the amount of nuclear hepatocyte nuclear factor-1&alpha
(HNF-1&alpha
), a major transcriptional regulator for activation of PCSK9 promoter, but not that of nuclear sterol-responsive element binding protein-2 (SREBP-2) in HepG2 cells. Finally, we identified the cajaninstilbene acid, a main bioactive stilbene component in MECC, which significantly modulated the LDLR and PCSK9 expression in HepG2 cells. Our current data suggest that the cajaninstilbene acid may contribute to the hypocholesterolemic activity of Cajanus cajan L. leaves. Our findings support that the extract of Cajanus cajan L. leaves may serve as a cholesterol-lowering agent.
Databáze: OpenAIRE
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