Cargando…
The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Cajanus cajan (L.) Millsp.) Leaves on Regulating LDLR and PCSK9 Expression in HepG2 Cells
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 ca...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385019/ https://www.ncbi.nlm.nih.gov/pubmed/30704067 http://dx.doi.org/10.3390/molecules24030493 |
_version_ | 1783397112427315200 |
---|---|
author | Chang, Heng-Yuan Wu, Jia-Ru Gao, Wan-Yun Lin, Huei-Ru Chen, Pei-Yi Chen, Chen-I Wu, Ming-Jiuan Yen, Jui-Hung |
author_facet | Chang, Heng-Yuan Wu, Jia-Ru Gao, Wan-Yun Lin, Huei-Ru Chen, Pei-Yi Chen, Chen-I Wu, Ming-Jiuan Yen, Jui-Hung |
author_sort | Chang, Heng-Yuan |
collection | PubMed |
description | 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-α (LXR-α) in HepG2 cells. Furthermore, we demonstrated that MECC down-regulated the PCSK9 gene expression through reducing the amount of nuclear hepatocyte nuclear factor-1α (HNF-1α), 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. |
format | Online Article Text |
id | pubmed-6385019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63850192019-02-23 The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Cajanus cajan (L.) Millsp.) Leaves on Regulating LDLR and PCSK9 Expression in HepG2 Cells Chang, Heng-Yuan Wu, Jia-Ru Gao, Wan-Yun Lin, Huei-Ru Chen, Pei-Yi Chen, Chen-I Wu, Ming-Jiuan Yen, Jui-Hung Molecules Article 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-α (LXR-α) in HepG2 cells. Furthermore, we demonstrated that MECC down-regulated the PCSK9 gene expression through reducing the amount of nuclear hepatocyte nuclear factor-1α (HNF-1α), 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. MDPI 2019-01-30 /pmc/articles/PMC6385019/ /pubmed/30704067 http://dx.doi.org/10.3390/molecules24030493 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chang, Heng-Yuan Wu, Jia-Ru Gao, Wan-Yun Lin, Huei-Ru Chen, Pei-Yi Chen, Chen-I Wu, Ming-Jiuan Yen, Jui-Hung The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Cajanus cajan (L.) Millsp.) Leaves on Regulating LDLR and PCSK9 Expression in HepG2 Cells |
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 |
title_full | The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Cajanus cajan (L.) Millsp.) Leaves on Regulating LDLR and PCSK9 Expression in HepG2 Cells |
title_fullStr | The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Cajanus cajan (L.) Millsp.) Leaves on Regulating LDLR and PCSK9 Expression in HepG2 Cells |
title_full_unstemmed | The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Cajanus cajan (L.) Millsp.) Leaves on Regulating LDLR and PCSK9 Expression in HepG2 Cells |
title_short | The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Cajanus cajan (L.) Millsp.) Leaves on Regulating LDLR and PCSK9 Expression in HepG2 Cells |
title_sort | cholesterol-modulating effect of methanol extract of pigeon pea (cajanus cajan (l.) millsp.) leaves on regulating ldlr and pcsk9 expression in hepg2 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385019/ https://www.ncbi.nlm.nih.gov/pubmed/30704067 http://dx.doi.org/10.3390/molecules24030493 |
work_keys_str_mv | AT changhengyuan thecholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT wujiaru thecholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT gaowanyun thecholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT linhueiru thecholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT chenpeiyi thecholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT chencheni thecholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT wumingjiuan thecholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT yenjuihung thecholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT changhengyuan cholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT wujiaru cholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT gaowanyun cholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT linhueiru cholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT chenpeiyi cholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT chencheni cholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT wumingjiuan cholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells AT yenjuihung cholesterolmodulatingeffectofmethanolextractofpigeonpeacajanuscajanlmillspleavesonregulatingldlrandpcsk9expressioninhepg2cells |