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(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway

An overload of hepatic fatty acids, such as oleic acid is a key trigger of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether Artemisia frigida, a valuable traditional medicine used to treat various diseases, could mitigate OA-induced lipid accumulation in HepG2 cells. Then, to...

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Autores principales: Xi, Yiyuan, Zheng, Jujia, Xie, Wei, Xu, Xiangwei, Cho, Namki, Zhou, Xudong, Yu, Xiaomin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640464/
https://www.ncbi.nlm.nih.gov/pubmed/34867358
http://dx.doi.org/10.3389/fphar.2021.750147
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author Xi, Yiyuan
Zheng, Jujia
Xie, Wei
Xu, Xiangwei
Cho, Namki
Zhou, Xudong
Yu, Xiaomin
author_facet Xi, Yiyuan
Zheng, Jujia
Xie, Wei
Xu, Xiangwei
Cho, Namki
Zhou, Xudong
Yu, Xiaomin
author_sort Xi, Yiyuan
collection PubMed
description An overload of hepatic fatty acids, such as oleic acid is a key trigger of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether Artemisia frigida, a valuable traditional medicine used to treat various diseases, could mitigate OA-induced lipid accumulation in HepG2 cells. Then, to identify the active substances in A. frigida, a phytochemistry investigation was conducted using a bioassay-guided isolation method. Consequently, one terpene (1) and one flavone (2) were identified. Compound 1 ((+)-dehydrovomifoliol) exhibited potent effects against lipid accumulation in OA-induced HepG2 cells, without causing cyto-toxicity. Notably, treatment with (+)-dehydrovomifoliol decreased the expression levels of three genes related to lipogenesis (SREBP1, ACC, and FASN) and increased those of three genes related to fatty acid oxidation (PPARα, ACOX1, and FGF21). In addition, similar results were observed for SREBP1, PPARα, and FGF21 protein levels. The effects of (+)-dehydrovomifoliol were partially reversed by treatment with the PPARα antagonist GW6471, indicating the important role of the PPARα–FGF21 axis in the effects of (+)-dehydrovomifoliol. Based on its effects on hepatic lipogenesis and fatty acid oxidation signaling via the PPARα–FGF21 axis, (+)-dehydrovomifoliol isolated from A. frigida could be a useful early lead compound for developing new drugs for NAFLD prevention.
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spelling pubmed-86404642021-12-04 (+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway Xi, Yiyuan Zheng, Jujia Xie, Wei Xu, Xiangwei Cho, Namki Zhou, Xudong Yu, Xiaomin Front Pharmacol Pharmacology An overload of hepatic fatty acids, such as oleic acid is a key trigger of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether Artemisia frigida, a valuable traditional medicine used to treat various diseases, could mitigate OA-induced lipid accumulation in HepG2 cells. Then, to identify the active substances in A. frigida, a phytochemistry investigation was conducted using a bioassay-guided isolation method. Consequently, one terpene (1) and one flavone (2) were identified. Compound 1 ((+)-dehydrovomifoliol) exhibited potent effects against lipid accumulation in OA-induced HepG2 cells, without causing cyto-toxicity. Notably, treatment with (+)-dehydrovomifoliol decreased the expression levels of three genes related to lipogenesis (SREBP1, ACC, and FASN) and increased those of three genes related to fatty acid oxidation (PPARα, ACOX1, and FGF21). In addition, similar results were observed for SREBP1, PPARα, and FGF21 protein levels. The effects of (+)-dehydrovomifoliol were partially reversed by treatment with the PPARα antagonist GW6471, indicating the important role of the PPARα–FGF21 axis in the effects of (+)-dehydrovomifoliol. Based on its effects on hepatic lipogenesis and fatty acid oxidation signaling via the PPARα–FGF21 axis, (+)-dehydrovomifoliol isolated from A. frigida could be a useful early lead compound for developing new drugs for NAFLD prevention. Frontiers Media S.A. 2021-11-19 /pmc/articles/PMC8640464/ /pubmed/34867358 http://dx.doi.org/10.3389/fphar.2021.750147 Text en Copyright © 2021 Xi, Zheng, Xie, Xu, Cho, Zhou and Yu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Xi, Yiyuan
Zheng, Jujia
Xie, Wei
Xu, Xiangwei
Cho, Namki
Zhou, Xudong
Yu, Xiaomin
(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway
title (+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway
title_full (+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway
title_fullStr (+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway
title_full_unstemmed (+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway
title_short (+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway
title_sort (+)-dehydrovomifoliol alleviates oleic acid-induced lipid accumulation in hepg2 cells via the pparα–fgf21 pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640464/
https://www.ncbi.nlm.nih.gov/pubmed/34867358
http://dx.doi.org/10.3389/fphar.2021.750147
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