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

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 autophagyapoptosis 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.