Paeoniflorin as a Promising Therapeutic Candidate in Intestinal Diseases: Experimental Evidence, Mechanistic Insights, and Translational Perspectives.

Intestinal diseases, including inflammatory bowel disease, functional bowel disorders, stress-related enteropathy, colorectal cancer, and colitis-associated colorectal cancer, share overlapping pathological processes such as epithelial barrier disruption, immune dysregulation, microbiota imbalance, oxidative stress, and inflammation-driven tissue injury. Paeoniflorin, a major monoterpene glycoside derived from Paeonia species, has attracted increasing attention because of its anti-inflammatory, antioxidant, immunomodulatory, anti-apoptotic, and barrier-protective properties. This review summarizes experimental evidence and mechanistic findings regarding the therapeutic potential of paeoniflorin in intestinal diseases. Current preclinical studies suggest that paeoniflorin can alleviate colitis, improve epithelial barrier integrity, promote mucosal repair, modulate microbiota-metabolite interactions, reduce visceral hypersensitivity, and suppress inflammation-associated colorectal tumorigenesis. Mechanistically, these effects involve coordinated regulation of inflammatory signaling, immune-cell balance, epithelial regeneration, gut-brain axis-related pathways, and oncogenic inflammatory cascades. Recent advances in colon-targeted delivery, pharmacokinetic modulation, compatibility-dependent exposure, and derivative development further support its translational potential. However, existing evidence remains largely based on in vitro and animal studies, with limited clinical data, heterogeneous models and dosing regimens, insufficient PK/PD validation, and unresolved druggability challenges. Future research should integrate mechanistic validation, optimized delivery systems, exposure-response evaluation, and clinically relevant disease stratification to support its progression from a bioactive natural compound to a viable intestinal therapeutic candidate.