{"title":"Integrative Investigation on the Mechanisms of Modified Zuojin Pill (SQQT) in Ameliorating Gastric Metaplasia.","authors":"Xuefei Yang, Jiaqi Zhang, Jing Ma, Jinke Huang, Ping Wang, Fengyun Wang, Xudong Tang","doi":"10.1016/j.jep.2025.119643","DOIUrl":null,"url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Zuojin pill is a well-known traditional Chinese medicine (TCM) for treating gastric disorders. The modified Zuojin pill (SQQT) has been used in the treatment of gastric metaplasia (GM) in China for decades. However, the mechanisms of SQQT treat GM remain unclear.</p><p><strong>Aim of the study: </strong>Our goals are to evaluate the effect of SQQT on GM and to investigate its potential mechanisms.</p><p><strong>Methods: </strong>An animal model of metaplasia was established to study the mechanism of SQQT. RNA-seq was employed to analyze the pathogenesis of GM. Network pharmacological approaches and molecular docking were used to elucidate the mechanisms of SQQT. Common targets of the SQQT and GM mechanism pathways are defined as the key mechanisms of SQQT's treatment in GM. The key mechanisms were validated through in vivo and in vitro experiments.</p><p><strong>Results: </strong>RNA-seq analysis of GM animals and network pharmacology of SQQT indicated that SQQT might treat GM via 20 pathways, including the PPAR pathway. Among the 3 core targets of the PPAR pathway, only PPARG is related to GM progression. Besides, the core components of SQQT have a lower affinity for binding to PPARG. The main mechanism of SQQT ameliorated GM is related to PPARG. In animal experiments, SQQT ameliorated GM through ROS decreasing, mitochondrial damage repairing, and protein marker rectification. In cell experiments, SQQT notably decreased the levels of ferroptosis and metaplasia markers including GPX4, PPARG, MUC6, and ACSL4.</p><p><strong>Conclusion: </strong>SQQT ameliorated gastric metaplasia by inhibiting the PPARG/ferroptosis pathway.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119643"},"PeriodicalIF":4.8000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2025.119643","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Ethnopharmacological relevance: Zuojin pill is a well-known traditional Chinese medicine (TCM) for treating gastric disorders. The modified Zuojin pill (SQQT) has been used in the treatment of gastric metaplasia (GM) in China for decades. However, the mechanisms of SQQT treat GM remain unclear.
Aim of the study: Our goals are to evaluate the effect of SQQT on GM and to investigate its potential mechanisms.
Methods: An animal model of metaplasia was established to study the mechanism of SQQT. RNA-seq was employed to analyze the pathogenesis of GM. Network pharmacological approaches and molecular docking were used to elucidate the mechanisms of SQQT. Common targets of the SQQT and GM mechanism pathways are defined as the key mechanisms of SQQT's treatment in GM. The key mechanisms were validated through in vivo and in vitro experiments.
Results: RNA-seq analysis of GM animals and network pharmacology of SQQT indicated that SQQT might treat GM via 20 pathways, including the PPAR pathway. Among the 3 core targets of the PPAR pathway, only PPARG is related to GM progression. Besides, the core components of SQQT have a lower affinity for binding to PPARG. The main mechanism of SQQT ameliorated GM is related to PPARG. In animal experiments, SQQT ameliorated GM through ROS decreasing, mitochondrial damage repairing, and protein marker rectification. In cell experiments, SQQT notably decreased the levels of ferroptosis and metaplasia markers including GPX4, PPARG, MUC6, and ACSL4.
Conclusion: SQQT ameliorated gastric metaplasia by inhibiting the PPARG/ferroptosis pathway.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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