Cargando…
(+)-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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1784609336139448320 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8640464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT xiyiyuan dehydrovomifoliolalleviatesoleicacidinducedlipidaccumulationinhepg2cellsviathepparafgf21pathway AT zhengjujia dehydrovomifoliolalleviatesoleicacidinducedlipidaccumulationinhepg2cellsviathepparafgf21pathway AT xiewei dehydrovomifoliolalleviatesoleicacidinducedlipidaccumulationinhepg2cellsviathepparafgf21pathway AT xuxiangwei dehydrovomifoliolalleviatesoleicacidinducedlipidaccumulationinhepg2cellsviathepparafgf21pathway AT chonamki dehydrovomifoliolalleviatesoleicacidinducedlipidaccumulationinhepg2cellsviathepparafgf21pathway AT zhouxudong dehydrovomifoliolalleviatesoleicacidinducedlipidaccumulationinhepg2cellsviathepparafgf21pathway AT yuxiaomin dehydrovomifoliolalleviatesoleicacidinducedlipidaccumulationinhepg2cellsviathepparafgf21pathway |