(+)-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:	Yiyuan Xi, Jujia Zheng, Wei Xie, Xiangwei Xu, Namki Cho, Xudong Zhou, Xiaomin Yu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	artemisia frigida non-alcoholic fatty liver disease peroxisome proliferator-activated receptorα lipid accumulation terpene Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/58940ecce84449039262013dc40af79d
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spelling	oai:doaj.org-article:58940ecce84449039262013dc40af79d2021-11-19T07:46:12Z(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway1663-981210.3389/fphar.2021.750147https://doaj.org/article/58940ecce84449039262013dc40af79d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.750147/fullhttps://doaj.org/toc/1663-9812An 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.Yiyuan XiYiyuan XiJujia ZhengWei XieXiangwei XuNamki ChoXudong ZhouXiaomin YuFrontiers Media S.A.articleartemisia frigidanon-alcoholic fatty liver diseaseperoxisome proliferator-activated receptorαlipid accumulationterpeneTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	artemisia frigida non-alcoholic fatty liver disease peroxisome proliferator-activated receptorα lipid accumulation terpene Therapeutics. Pharmacology RM1-950
spellingShingle	artemisia frigida non-alcoholic fatty liver disease peroxisome proliferator-activated receptorα lipid accumulation terpene Therapeutics. Pharmacology RM1-950 Yiyuan Xi Yiyuan Xi Jujia Zheng Wei Xie Xiangwei Xu Namki Cho Xudong Zhou Xiaomin Yu (+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway
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.
format	article
author	Yiyuan Xi Yiyuan Xi Jujia Zheng Wei Xie Xiangwei Xu Namki Cho Xudong Zhou Xiaomin Yu
author_facet	Yiyuan Xi Yiyuan Xi Jujia Zheng Wei Xie Xiangwei Xu Namki Cho Xudong Zhou Xiaomin Yu
author_sort	Yiyuan Xi
title	(+)-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_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_sort	(+)-dehydrovomifoliol alleviates oleic acid-induced lipid accumulation in hepg2 cells via the pparα–fgf21 pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/58940ecce84449039262013dc40af79d
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(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway

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