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中药对胃肠动力障碍中Cajal间质细胞自噬与凋亡相互作用调控的研究进展

Research progress on the regulation of interstitial cell of Cajal autophagy and apoptosis crosstalk by traditional Chinese medicine in gastrointestinal motility disorders.

作者信息

Zhang Lumei, Song Zhongyang, Huang Xixi, Jiang Bing, Shen Yanyun, Li Xinyu, Jiang Xiaoxue, Wan Jiayi, Xu Qian, Liu Qian, He Zhaxicao, Zhao Bing, Li Jingwei, Yan Jingnan, Zhang Zhiming, Wang Zhigang

机构信息

Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, China; Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu, 730000, China.

Gansu University of Traditional Chinese Medicine Affiliated Hospital, Lanzhou, Gansu, 730000, China; Gansu Research Institute of Cardiovascular Diseases, Lanzhou, Gansu, 730000, China.

出版信息

J Ethnopharmacol. 2025 Jun 11;351:120128. doi: 10.1016/j.jep.2025.120128.


DOI:10.1016/j.jep.2025.120128
PMID:40513924
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrointestinal motility disorders (GMD) severely impact quality of life, with rising global prevalence linked to modern dietary and lifestyle changes. Traditional Chinese medicine (TCM), rooted in the "holistic regulation" philosophy and centuries of empirical application, demonstrates unique advantages in restoring gastrointestinal homeostasis. Historical records and modern clinical practices validate the efficacy of herbal compounds, bioactive phytochemicals, and external therapies in modulating intestinal pacemaker systems. AIM OF THE STUDY: This study aims to systematically review the pathogenesis of GMD mediated by autophagy-apoptosis imbalance in interstitial cells of Cajal (ICCs), examine the therapeutic application of traditional Chinese medicine (TCM) interventions, and identify the bioactive components and molecular mechanisms underlying TCM's regulatory effects on ICCs homeostasis. METHODS: Utilize PubMed and NCBI databases to conduct a comprehensive search on GMD, focusing on diseases such as slow transit constipation (STC), functional dyspepsia (FD), diabetic gastroparesis (DGP), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), functional constipation (FC) and opioid-induced constipation (OIC). Additionally, explore the underlying mechanisms involving autophagy, apoptosis, molecular crosstalk, and ICC dynamics. Investigate the potential therapeutic effects of herbal medicine, TCM compounds, bioactive phytocompounds, and external TCM therapeutic modalities on these GMD. RESULTS: The study systematically identified 24 TCM compound formulations, 3 bioactive herbal extracts, and 10 specific active components, along with external therapeutic modalities including electroacupuncture (EA) and acupuncture. These therapeutic agents demonstrated multi-pathway regulatory effects by modulating autophagy-apoptosis dynamics in ICCs, with mechanistic analyses revealing their capacity to coordinate multiple signaling pathways for restoring gastrointestinal (GI) motility homeostasis. CONCLUSION: TCM and external therapies demonstrate significant therapeutic efficacy in ameliorating GMD. The underlying molecular mechanisms may involve the coordinated modulation of a multi-target regulatory network that restores autophagy-apoptosis homeostasis in ICCs. Given the specificity and adaptability of this mechanistic framework, future research should prioritize the development of active constituents and their corresponding molecular targets as novel therapeutic agents and intervention points. These findings provide both a theoretical foundation and translational directions for advancing precision-targeted strategies in GI motility regulation.

摘要

民族药理学相关性:胃肠动力障碍(GMD)严重影响生活质量,全球患病率上升与现代饮食和生活方式的改变有关。传统中医(TCM)植根于“整体调节”理念和数百年的经验应用,在恢复胃肠内环境稳态方面具有独特优势。历史记录和现代临床实践证实了草药化合物、生物活性植物化学物质及外部疗法在调节肠道起搏器系统方面的功效。 研究目的:本研究旨在系统综述由Cajal间质细胞(ICC)自噬 - 凋亡失衡介导的GMD发病机制,研究中医干预措施的治疗应用,并确定中药对ICC内环境稳态调节作用的生物活性成分及分子机制。 方法:利用PubMed和NCBI数据库对GMD进行全面检索,重点关注慢传输型便秘(STC)、功能性消化不良(FD)、糖尿病胃轻瘫(DGP)、胃食管反流病(GERD)、肠易激综合征(IBS)、功能性便秘(FC)和阿片类药物所致便秘(OIC)等疾病。此外,探讨涉及自噬、凋亡、分子串扰和ICC动态变化的潜在机制。研究草药、中药复方、生物活性植物化合物及中医外部治疗方式对这些GMD的潜在治疗作用。 结果:该研究系统鉴定出24种中药复方制剂、3种生物活性草药提取物和10种特定活性成分,以及包括电针(EA)和针刺在内的外部治疗方式。这些治疗药物通过调节ICC中的自噬 - 凋亡动态发挥多途径调节作用,机制分析表明它们有能力协调多种信号通路以恢复胃肠(GI)动力稳态。 结论:中医及外部疗法在改善GMD方面显示出显著的治疗效果。潜在的分子机制可能涉及协调调节多靶点调控网络,从而恢复ICC中的自噬 - 凋亡稳态。鉴于这一机制框架的特异性和适应性,未来研究应优先开发活性成分及其相应的分子靶点,作为新型治疗药物和干预点。这些发现为推进胃肠动力调节的精准靶向策略提供了理论基础和转化方向。

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