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Effects of Poria cocos extract on metabolic dysfunction-associated fatty liver disease via the FXR/PPARα-SREBPs pathway

Despite the increase in the global prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD), no approved drug currently exists for the disease. Poria cocos (Schw.) Wolf (P. cocos) is a medicinal mushroom belonging to a family of polyporaceae widely used in TCM clinics to protect th...

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Autores principales: He, Jinbiao, Yang, Yu, Zhang, Fan, Li, Yanjuan, Li, Xiaosi, Pu, Xuemei, He, Xudong, Zhang, Mei, Yang, Xinxing, Yu, Qiuman, Qi, Yan, Li, Xuefang, Yu, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581278/
https://www.ncbi.nlm.nih.gov/pubmed/36278226
http://dx.doi.org/10.3389/fphar.2022.1007274
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author He, Jinbiao
Yang, Yu
Zhang, Fan
Li, Yanjuan
Li, Xiaosi
Pu, Xuemei
He, Xudong
Zhang, Mei
Yang, Xinxing
Yu, Qiuman
Qi, Yan
Li, Xuefang
Yu, Jie
author_facet He, Jinbiao
Yang, Yu
Zhang, Fan
Li, Yanjuan
Li, Xiaosi
Pu, Xuemei
He, Xudong
Zhang, Mei
Yang, Xinxing
Yu, Qiuman
Qi, Yan
Li, Xuefang
Yu, Jie
author_sort He, Jinbiao
collection PubMed
description Despite the increase in the global prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD), no approved drug currently exists for the disease. Poria cocos (Schw.) Wolf (P. cocos) is a medicinal mushroom belonging to a family of polyporaceae widely used in TCM clinics to protect the liver and treat obesity. However, its efficacy, practical components, and underlying mechanism against MAFLD are yet to be determined. In this study, we evaluated the effects of Poria cocos (P. cocos) ethanol extract (EPC) on hepatic dyslipidemia, steatosis, and inflammation by both bioinformatics analysis and MAFLD rats induced by HFD feeding. We found EPC treatment dramatically reduced lipid accumulation, inflammatory cell infiltration, and liver injury. EPC reduced serum TC, TG levels, and hepatic TG, TBA, and NEFA contents. UHPLC Q-Trap/MS examination of BA profiles in serum and feces showed that EPC increased fecal conjugated BAs, decreased free BAs, and improved BA metabolism in HFD-fed rats. Western blot and RT-qPCR analysis showed that EPC could activate hepatic FXR and PPARα expression and reduce CYP7A1 and SREBP-1c expression. Systemic pharmacology combined with molecular docking suggested that poricoic acid B and polyporenic acid C, the major active compounds in EPC, could ameliorate lipid homeostasis by activating the nuclear receptor PPARα. We further confirmed their inhibition effects of lipid droplet deposition in steatized L-02 hepatocytes. In summary, EPC alleviated HFD-induced MAFLD by regulating lipid homeostasis and BA metabolism via the FXR/PPARα-SREBPs signaling pathway. P. cocos triterpenes, such as poricoic acid B and polyporenic acid C, were the characteristic substances of P. cocos for the treatment of MAFLD.
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spelling pubmed-95812782022-10-20 Effects of Poria cocos extract on metabolic dysfunction-associated fatty liver disease via the FXR/PPARα-SREBPs pathway He, Jinbiao Yang, Yu Zhang, Fan Li, Yanjuan Li, Xiaosi Pu, Xuemei He, Xudong Zhang, Mei Yang, Xinxing Yu, Qiuman Qi, Yan Li, Xuefang Yu, Jie Front Pharmacol Pharmacology Despite the increase in the global prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD), no approved drug currently exists for the disease. Poria cocos (Schw.) Wolf (P. cocos) is a medicinal mushroom belonging to a family of polyporaceae widely used in TCM clinics to protect the liver and treat obesity. However, its efficacy, practical components, and underlying mechanism against MAFLD are yet to be determined. In this study, we evaluated the effects of Poria cocos (P. cocos) ethanol extract (EPC) on hepatic dyslipidemia, steatosis, and inflammation by both bioinformatics analysis and MAFLD rats induced by HFD feeding. We found EPC treatment dramatically reduced lipid accumulation, inflammatory cell infiltration, and liver injury. EPC reduced serum TC, TG levels, and hepatic TG, TBA, and NEFA contents. UHPLC Q-Trap/MS examination of BA profiles in serum and feces showed that EPC increased fecal conjugated BAs, decreased free BAs, and improved BA metabolism in HFD-fed rats. Western blot and RT-qPCR analysis showed that EPC could activate hepatic FXR and PPARα expression and reduce CYP7A1 and SREBP-1c expression. Systemic pharmacology combined with molecular docking suggested that poricoic acid B and polyporenic acid C, the major active compounds in EPC, could ameliorate lipid homeostasis by activating the nuclear receptor PPARα. We further confirmed their inhibition effects of lipid droplet deposition in steatized L-02 hepatocytes. In summary, EPC alleviated HFD-induced MAFLD by regulating lipid homeostasis and BA metabolism via the FXR/PPARα-SREBPs signaling pathway. P. cocos triterpenes, such as poricoic acid B and polyporenic acid C, were the characteristic substances of P. cocos for the treatment of MAFLD. Frontiers Media S.A. 2022-10-05 /pmc/articles/PMC9581278/ /pubmed/36278226 http://dx.doi.org/10.3389/fphar.2022.1007274 Text en Copyright © 2022 He, Yang, Zhang, Li, Li, Pu, He, Zhang, Yang, Yu, Qi, Li 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
He, Jinbiao
Yang, Yu
Zhang, Fan
Li, Yanjuan
Li, Xiaosi
Pu, Xuemei
He, Xudong
Zhang, Mei
Yang, Xinxing
Yu, Qiuman
Qi, Yan
Li, Xuefang
Yu, Jie
Effects of Poria cocos extract on metabolic dysfunction-associated fatty liver disease via the FXR/PPARα-SREBPs pathway
title Effects of Poria cocos extract on metabolic dysfunction-associated fatty liver disease via the FXR/PPARα-SREBPs pathway
title_full Effects of Poria cocos extract on metabolic dysfunction-associated fatty liver disease via the FXR/PPARα-SREBPs pathway
title_fullStr Effects of Poria cocos extract on metabolic dysfunction-associated fatty liver disease via the FXR/PPARα-SREBPs pathway
title_full_unstemmed Effects of Poria cocos extract on metabolic dysfunction-associated fatty liver disease via the FXR/PPARα-SREBPs pathway
title_short Effects of Poria cocos extract on metabolic dysfunction-associated fatty liver disease via the FXR/PPARα-SREBPs pathway
title_sort effects of poria cocos extract on metabolic dysfunction-associated fatty liver disease via the fxr/pparα-srebps pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581278/
https://www.ncbi.nlm.nih.gov/pubmed/36278226
http://dx.doi.org/10.3389/fphar.2022.1007274
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