Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cells

Abstract Background Crocin (CRO), chlorogenic acid (CGA), geniposide (GEN), and quercetin (QUE) are all natural compounds with anti-obesity properties, in particular, hypolipidemic effects, which have been widely used for the treatment of obesity-related metabolic diseases. However, it is not yet kn...

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Main Authors: Ennian Leng, Yuan Xiao, Zhentao Mo, Yiqi Li, Yueyue Zhang, Xiaosi Deng, Min Zhou, Chaochao Zhou, Zengxuan He, Jingyi He, Lu Xiao, Junming Li, Wenna Li
Format: Article
Language:English
Published: BioMed Central 2018-04-01
Series:BMC Complementary and Alternative Medicine
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12906-018-2189-6
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spelling doaj-art-d04ed4853c7c4c09982d451313d6cab42018-08-16T01:31:54ZengBioMed CentralBMC Complementary and Alternative Medicine1472-68822018-04-0118111010.1186/s12906-018-2189-6Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cellsEnnian Leng0Yuan Xiao1Zhentao Mo2Yiqi Li3Yueyue Zhang4Xiaosi Deng5Min Zhou6Chaochao Zhou7Zengxuan He8Jingyi He9Lu Xiao10Junming Li11Wenna Li12Zhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityZhuhai Campus, Zunyi Medical UniversityAbstract Background Crocin (CRO), chlorogenic acid (CGA), geniposide (GEN), and quercetin (QUE) are all natural compounds with anti-obesity properties, in particular, hypolipidemic effects, which have been widely used for the treatment of obesity-related metabolic diseases. However, it is not yet known whether these compounds interact synergistically. Here, we investigated the effects and molecular mechanisms of CRO, CGA, GEN, QUE, and a combination of all four compounds (CCGQ), on lipid accumulation in human hepatoma (HepG2 cells). Methods The optimal concentration of CRO, CGA, GEN, QUE to stimulate HepG2 cells proliferation was determined using MTT assay. HepG2 cells were pretreated with 10 μmol/L simvastatin, 1 μmol/L CRO, 30 μmol/L CGA, 10 μmol/L GEN, 10 μmol/L QUE, and CCGQ (a combination of 1 μmol/L CRO, 30 μmol/L CGA, 10 μmol/L GEN, and 10 μmol/L QUE) for 24 or 48 h. Oil red O staining and extracellular TC and TG levels were detected. The RT-PCR was used to observe on cholesterol metabolism-related gene expression. Immunocytochemistry and western-blot assayed the 3-hydroxy-3-methylglutaryl-coenzyme (HMGCR) protein expression in HepG2 cells. Results Compared to those of control, we demonstrated that treating HepG2 cells for 48 h with CCGQ resulted in a strong synergistic effect, causing a marked decrease in lipid deposition in comparison to individual treatments, in both triglyceride and total cholesterol (CRO, 5.74- and 1.49-folds; CGA, 3.38- and 1.12-folds; GEN, 4.04- and 1.44-folds; QUE, 3.36- and 1.24-folds; simvastatin, 5.49- and 1.83-folds; and CCGQ, 7.75- and 2.20-folds), and Oil red O staining assays. In addition, CCGQ treatment increased ATP-binding cassette transporter (ABCA1), cholesterol 7α-hydroxylase (CYP7A1), and AMP-activated protein kinase 2α (AMPKα2) mRNA expression, while decreasing sterol regulatory element binding protein 2 (SREBP2), and liver X receptor alpha (LXRα) mRNA expression. Notably, CCGQ was more effective in decreasing HMGCR expression than the individual treatments. Conclusion The CCGQ combination has potential, both as a complementary therapy for hyperlipemia, and in preventing further obesity-related complications.http://link.springer.com/article/10.1186/s12906-018-2189-6CrocinChlorogenic acidGeniposideQuercetinSynergistic interactionLipid accumulation
institution Open Data Bank
collection Open Access Journals
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language English
format Article
author Ennian Leng
Yuan Xiao
Zhentao Mo
Yiqi Li
Yueyue Zhang
Xiaosi Deng
Min Zhou
Chaochao Zhou
Zengxuan He
Jingyi He
Lu Xiao
Junming Li
Wenna Li
spellingShingle Ennian Leng
Yuan Xiao
Zhentao Mo
Yiqi Li
Yueyue Zhang
Xiaosi Deng
Min Zhou
Chaochao Zhou
Zengxuan He
Jingyi He
Lu Xiao
Junming Li
Wenna Li
Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cells
BMC Complementary and Alternative Medicine
Crocin
Chlorogenic acid
Geniposide
Quercetin
Synergistic interaction
Lipid accumulation
author_facet Ennian Leng
Yuan Xiao
Zhentao Mo
Yiqi Li
Yueyue Zhang
Xiaosi Deng
Min Zhou
Chaochao Zhou
Zengxuan He
Jingyi He
Lu Xiao
Junming Li
Wenna Li
author_sort Ennian Leng
title Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cells
title_short Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cells
title_full Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cells
title_fullStr Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cells
title_full_unstemmed Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cells
title_sort synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in hepg2 cells
publisher BioMed Central
series BMC Complementary and Alternative Medicine
issn 1472-6882
publishDate 2018-04-01
description Abstract Background Crocin (CRO), chlorogenic acid (CGA), geniposide (GEN), and quercetin (QUE) are all natural compounds with anti-obesity properties, in particular, hypolipidemic effects, which have been widely used for the treatment of obesity-related metabolic diseases. However, it is not yet known whether these compounds interact synergistically. Here, we investigated the effects and molecular mechanisms of CRO, CGA, GEN, QUE, and a combination of all four compounds (CCGQ), on lipid accumulation in human hepatoma (HepG2 cells). Methods The optimal concentration of CRO, CGA, GEN, QUE to stimulate HepG2 cells proliferation was determined using MTT assay. HepG2 cells were pretreated with 10 μmol/L simvastatin, 1 μmol/L CRO, 30 μmol/L CGA, 10 μmol/L GEN, 10 μmol/L QUE, and CCGQ (a combination of 1 μmol/L CRO, 30 μmol/L CGA, 10 μmol/L GEN, and 10 μmol/L QUE) for 24 or 48 h. Oil red O staining and extracellular TC and TG levels were detected. The RT-PCR was used to observe on cholesterol metabolism-related gene expression. Immunocytochemistry and western-blot assayed the 3-hydroxy-3-methylglutaryl-coenzyme (HMGCR) protein expression in HepG2 cells. Results Compared to those of control, we demonstrated that treating HepG2 cells for 48 h with CCGQ resulted in a strong synergistic effect, causing a marked decrease in lipid deposition in comparison to individual treatments, in both triglyceride and total cholesterol (CRO, 5.74- and 1.49-folds; CGA, 3.38- and 1.12-folds; GEN, 4.04- and 1.44-folds; QUE, 3.36- and 1.24-folds; simvastatin, 5.49- and 1.83-folds; and CCGQ, 7.75- and 2.20-folds), and Oil red O staining assays. In addition, CCGQ treatment increased ATP-binding cassette transporter (ABCA1), cholesterol 7α-hydroxylase (CYP7A1), and AMP-activated protein kinase 2α (AMPKα2) mRNA expression, while decreasing sterol regulatory element binding protein 2 (SREBP2), and liver X receptor alpha (LXRα) mRNA expression. Notably, CCGQ was more effective in decreasing HMGCR expression than the individual treatments. Conclusion The CCGQ combination has potential, both as a complementary therapy for hyperlipemia, and in preventing further obesity-related complications.
topic Crocin
Chlorogenic acid
Geniposide
Quercetin
Synergistic interaction
Lipid accumulation
url http://link.springer.com/article/10.1186/s12906-018-2189-6
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