首页|Huatan Qushi formula alleviates non-alcoholic fatty liver disease via PI3K/Akt signaling and gut microbiota modulation

Huatan Qushi formula alleviates non-alcoholic fatty liver disease via PI3K/Akt signaling and gut microbiota modulation

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
Objective:To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula(HTQS for-mula),for the health management and treatment of non-alcoholic fatty liver disease(NAFLD).Methods:A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula.In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC-MS/MS combined with network pharmacology.The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot.Finally,16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids(SCFAs)and bile acids to determine the impact of the HTQS formula on gut microbiota.Results:The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol(TC),triglycerides,blood glucose,and insulin resistance(IR)without causing liver or kidney injury.We detected 28 components using UPLC-MS/MS and identified 439 shared targets be-tween NAFLD and the HTQS formula.Primarily,we focused on the PI3K/Akt signaling pathway based on protein-protein interaction network analysis.We validated that the HTQS formula inhibited liver stea-tosis and inflammation by increasing the phosphorylation levels of PI3K,AKT,P27,GSK3β in the PI3K/Akt signaling pathway.16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_ⅩⅢ_AD3011_group,which was positively correlated with IR and taurodeoxycholic acid.In addition,Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids,which could be essential to the therapeutic effect of the HTQS formula against NAFLD.Conclusions:The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury.Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Non-alcoholic fatty liver diseaseHuatan Qushi formulaNetwork pharmacologyPl3K/Akt signaling pathway16S rRNA sequencingGut microbiota

Xiuping Zhang、Linghui Zhu、Jinchen Ma、Yi Zheng、Xuejing Yang、Lingling Yang、Yang Dong、Yan Zhang、Baoxing Liu、Lingru Li

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Department of Gynecology,Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing,100029,China

School of Traditional Chinese Medicine.Beijing University of Chinese Medicine,Beijing 102488,China

School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China

Memorial Sloan Kettering Cancer Center,1275 York Avenue,New York,NY 10065,USA

Department of Hepatobiliary,Spleen,and Stomach Diseases,Henan Province Hospital of TCM,Zhengzhou,450002,China

Monitoring and Statistical Research Center,National Administration of Traditional Chinese Medicine,Beijing 100027,China

National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Diseases,Beijing University of Chinese Medicine,Beijing 100029,China

Department of Andrology,China-Japan Friendship Hospital,Beijing,100029,China

National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Diseases,Beijing University of Chinese Medicine,Beijing,100029,China

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2024

10.1016/j.jtcms.2024.08.004

中医科学杂志(英文)
北京中医药大学,清华大学出版社有限公司

中医科学杂志(英文)

ISSN：2095-7548
年,卷(期)：2024.11(4)