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

doi:10.3390/molecules24030493

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Title:	The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Cajanus cajan (L.) Millsp.) Leaves on Regulating LDLR and PCSK9 Expression in HepG2 Cells
Authors:	Chang, Heng-Yuan Wu, Jia-Ru Gao, Wan-Yun Lin, Huei-Ru Chen, Pei-Yi Chen, Chen-I Ming-Jiuan Wu(吳明娟) Yen, Jui-Hung
Contributors:	Tzu Chi Univ, Sch Postbaccalaureate Chinese Med Tzu Chi Univ, Dept Mol Biol & Human Genet Tzu Chi Univ, Dept Lab Med & Biotechnol Buddhist Tzu Chi Gen Hosp, Ctr Med Genet Taitung Dist Agr Res & Extens Stn, Crop Improvement Dept Chia Nan Univ Pharm & Sci, Dept Biotechnol
Keywords:	Cajanus cajan (L.) Millsp. LDLR PCSK9 HNF-1 alpha cajaninstilbene acid
Date:	2019-02
Issue Date:	2020-07-29 13:48:37 (UTC+8)
Publisher:	MDPI
Abstract:	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-) in HepG2 cells. Furthermore, we demonstrated that MECC down-regulated the PCSK9 gene expression through reducing the amount of nuclear hepatocyte nuclear factor-1 (HNF-1), 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.
Relation:	Molecules, v.24, n.3, 493
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles

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