Autophagy modulation in ulcerative colitis with traditional Chinese medicine: A review

Ulcerative colitis (UC) is a diffuse inflammatory disease that affects the rectum and colon. Management predominantly relies on pharmacotherapy, but challenges related to the side effects, hormone dependence, and drug resistance remain unresolved. Recent studies have identified autophagy as a promising therapeutic target in UC. Accumulating evidence indicates that Traditional Chinese Medicine (TCM) exerts therapeutic effects through the modulation of autophagy-related pathways. However, the underlying mechanisms remain fragmented and have not been systematically integrated. Therefore, a comprehensive review of the role of autophagy in TCM-mediated UC treatment is timely and warranted.

Autophagy, a critical mechanism for maintaining cellular homeostasis, plays a significant role in intestinal mucosal integrity, inflammation, and immune regulation. Dysregulated autophagy can lead to intestinal barrier damage and immune imbalance, thereby aggravating UC. TCM alleviates UC by modulating autophagy to restore intestinal environmental homeostasis. Evidence indicates that autophagy interacts with endoplasmic reticulum (ER) stress, gut microbiota, oxidative stress, inflammation, and associated signaling pathways, collectively influencing the pathogenesis of UC. TCM possesses the potential to exert therapeutic effects on UC by modulating autophagy through various interventions, including herbal formulations, active ingredients, plant-derived nanovesicles (PDNVs), acupuncture, and tuina. These interventions modulate the autophagy related signaling pathways such as AMPK/mTOR, PI3K/AKT, NLRP3, and Nrf2/HO-1, while regulating mitochondrial function, ER stress, and gut microbial balance.

The review summarizes current evidence regarding the molecular mechanisms by which TCM regulates autophagy in UC and highlights emerging therapeutic strategies and research trends. By integrating these findings in the field, it provides a theoretical foundation for optimizing TCM-based interventions and identifies future directions for the development of novel multitarget therapies targeting autophagy in UC.