Integrative investigation on the mechanisms of modified Zuojin pill (SQQT) in ameliorating gastric metaplasia

IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2025-04-25 Epub Date: 2025-03-18 DOI:10.1016/j.jep.2025.119643
Xuefei Yang , Jiaqi Zhang , Jing Ma , Jinke Huang , Ping Wang , Fengyun Wang , Xudong Tang
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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.

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加减左金丸改善胃化生作用机制的综合研究。
民族药理学相关性:左金丸是治疗胃病的著名中药。经改良的左金丸(SQQT)在中国用于治疗胃化生(GM)已有几十年的历史。然而,SQQT治疗GM的机制尚不清楚。研究目的:我们的目标是评估SQQT对GM的影响,并探讨其潜在机制。方法:建立化生动物模型,研究SQQT的作用机制。采用RNA-seq方法分析GM的发病机制,采用网络药理学方法和分子对接方法阐明SQQT的机制。将SQQT和GM机制通路的共同靶点定义为SQQT治疗GM的关键机制。通过体内和体外实验验证了SQQT治疗GM的关键机制。结果:转基因动物RNA-seq分析和SQQT网络药理学分析表明,SQQT可能通过包括PPAR途径在内的20条通路治疗转基因。在PPAR通路的3个核心靶点中,只有PPAR与GM进展有关。此外,SQQT的核心组件对PPARG的绑定亲和力较低。SQQT改良GM的主要机制与PPARG有关。在动物实验中,SQQT通过降低ROS、修复线粒体损伤和纠正蛋白质标记来改善转基因。在细胞实验中,SQQT显著降低了铁下垂和化生标志物的水平,包括GPX4、ppar、MUC6和ACSL4。结论:SQQT通过抑制PPARG/铁下垂途径改善胃化生。
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来源期刊
Journal of ethnopharmacology
Journal of ethnopharmacology 医学-全科医学与补充医学
CiteScore
10.30
自引率
5.60%
发文量
967
审稿时长
77 days
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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