Ethanol extract of Polygonatum cyrtonema Hua mitigates non-alcoholic steatohepatitis in mice

BackgroundPolygonum cyrtonema Hua is a kind of traditional Chinese botanic drug. Modern pharmacological research has confirmed that Polygonum cyrtonema Hua is able to alleviate nonalcoholic fatty liver disease, but the precise mechanism requires further investigation. This study investigated the pro...

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Main Authors: Dongliang Chen, Yue Shen, Fang Huang, Bo Huang, Shangfu Xu, Lisheng Li, Jie Liu, Zheng Li, Xia Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1487738/full
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author Dongliang Chen
Yue Shen
Yue Shen
Fang Huang
Bo Huang
Shangfu Xu
Shangfu Xu
Lisheng Li
Lisheng Li
Jie Liu
Zheng Li
Xia Li
author_facet Dongliang Chen
Yue Shen
Yue Shen
Fang Huang
Bo Huang
Shangfu Xu
Shangfu Xu
Lisheng Li
Lisheng Li
Jie Liu
Zheng Li
Xia Li
author_sort Dongliang Chen
collection DOAJ
description BackgroundPolygonum cyrtonema Hua is a kind of traditional Chinese botanic drug. Modern pharmacological research has confirmed that Polygonum cyrtonema Hua is able to alleviate nonalcoholic fatty liver disease, but the precise mechanism requires further investigation. This study investigated the protective effects and underlying mechanisms of Polygonatum cyrtonema ethanol extract (PCE) against Non-alcoholic steatohepatitis (NASH) in mice.MethodsUHPLC-MS/MS was utilized to analyze the metabolites of PCE. The NASH mouse model was establishment in C57BL/6J mice via high-fat diet (HFD) feeding for 12 weeks, and from the 9th week, mice were gavaged with PCE (100, 300, and 900 mg/kg/day), simvastatin (4 mg/kg) or saline. One hand, liver injury was assessed by serum enzymes, biochemistry, and histopathology; On the other hand, RNA-seq, qPCR, and Western blot were employed to investigate the related molecular mechanisms.Results211 metabolites were identified through UHPLC-MS/MS analysis. PCE ameliorated HFD induced liver injury and improved hepatocellular degeneration and steatosis in a dose-dependent way. PCE restored the expression of AMPK, SIRT1, SREBP1 and PPAR-α both in mRNA and protein levels. RNAseq identified unique gene expression profiles in response to high-fat diet (HFD) compared to the PCE treatments. HFD-induced DEGs were attenuated or abolished following PCE treatments. Ingenuity pathway analysis of RNA-seq data revealed key canonical pathways and upstream molecules regulated by PCE.ConclusionOur findings confirm the ability of PCE in alleviating NASH and underscores AMPK/SIRT1 pathway as a potential theraputic target for NASH treatment.
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publisher Frontiers Media S.A.
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spelling doaj-art-6501de7a216f4e1e99d4276bf296ea1f2025-01-30T06:23:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.14877381487738Ethanol extract of Polygonatum cyrtonema Hua mitigates non-alcoholic steatohepatitis in miceDongliang Chen0Yue Shen1Yue Shen2Fang Huang3Bo Huang4Shangfu Xu5Shangfu Xu6Lisheng Li7Lisheng Li8Jie Liu9Zheng Li10Xia Li11Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, ChinaDepartment of Pharmacy, Bijie City Qixingguan District Hospital of Traditional Chinese Medicine, Bijie, Guizhou, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, ChinaKey Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, ChinaDepartment of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, ChinaBackgroundPolygonum cyrtonema Hua is a kind of traditional Chinese botanic drug. Modern pharmacological research has confirmed that Polygonum cyrtonema Hua is able to alleviate nonalcoholic fatty liver disease, but the precise mechanism requires further investigation. This study investigated the protective effects and underlying mechanisms of Polygonatum cyrtonema ethanol extract (PCE) against Non-alcoholic steatohepatitis (NASH) in mice.MethodsUHPLC-MS/MS was utilized to analyze the metabolites of PCE. The NASH mouse model was establishment in C57BL/6J mice via high-fat diet (HFD) feeding for 12 weeks, and from the 9th week, mice were gavaged with PCE (100, 300, and 900 mg/kg/day), simvastatin (4 mg/kg) or saline. One hand, liver injury was assessed by serum enzymes, biochemistry, and histopathology; On the other hand, RNA-seq, qPCR, and Western blot were employed to investigate the related molecular mechanisms.Results211 metabolites were identified through UHPLC-MS/MS analysis. PCE ameliorated HFD induced liver injury and improved hepatocellular degeneration and steatosis in a dose-dependent way. PCE restored the expression of AMPK, SIRT1, SREBP1 and PPAR-α both in mRNA and protein levels. RNAseq identified unique gene expression profiles in response to high-fat diet (HFD) compared to the PCE treatments. HFD-induced DEGs were attenuated or abolished following PCE treatments. Ingenuity pathway analysis of RNA-seq data revealed key canonical pathways and upstream molecules regulated by PCE.ConclusionOur findings confirm the ability of PCE in alleviating NASH and underscores AMPK/SIRT1 pathway as a potential theraputic target for NASH treatment.https://www.frontiersin.org/articles/10.3389/fphar.2024.1487738/fullPolygonatum cyrtonema HuaNASHAMPKSIRT1NF-κ BPPAR-α
spellingShingle Dongliang Chen
Yue Shen
Yue Shen
Fang Huang
Bo Huang
Shangfu Xu
Shangfu Xu
Lisheng Li
Lisheng Li
Jie Liu
Zheng Li
Xia Li
Ethanol extract of Polygonatum cyrtonema Hua mitigates non-alcoholic steatohepatitis in mice
Frontiers in Pharmacology
Polygonatum cyrtonema Hua
NASH
AMPK
SIRT1
NF-κ B
PPAR-α
title Ethanol extract of Polygonatum cyrtonema Hua mitigates non-alcoholic steatohepatitis in mice
title_full Ethanol extract of Polygonatum cyrtonema Hua mitigates non-alcoholic steatohepatitis in mice
title_fullStr Ethanol extract of Polygonatum cyrtonema Hua mitigates non-alcoholic steatohepatitis in mice
title_full_unstemmed Ethanol extract of Polygonatum cyrtonema Hua mitigates non-alcoholic steatohepatitis in mice
title_short Ethanol extract of Polygonatum cyrtonema Hua mitigates non-alcoholic steatohepatitis in mice
title_sort ethanol extract of polygonatum cyrtonema hua mitigates non alcoholic steatohepatitis in mice
topic Polygonatum cyrtonema Hua
NASH
AMPK
SIRT1
NF-κ B
PPAR-α
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1487738/full
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