Recent Advances in Natural Products for Colitis: Mechanisms and Translational Perspectives

Colitis is a chronic relapsing inflammatory disorder characterized by persistent mucosal inflammation, epithelial barrier disruption, oxidative stress, immune dysregulation, and gut microbiota imbalance. Although current therapies have improved disease management, their long-term use is still limited by incomplete response, relapse, adverse effects, and high cost. Natural products have attracted increasing attention as promising candidates for colitis intervention because of their structural diversity, broad bioactivity, and multitarget regulatory potential. In veterinary medicine, colitis and colitis-related intestinal inflammatory disorders are also clinically relevant in companion animals, horses, and food-producing animals, where they contribute to diarrhea, impaired intestinal barrier function, reduced performance, treatment costs, and antimicrobial-use concerns. Therefore, natural products may have additional value as adjunctive, nutritional, or microbiota-modulating strategies in veterinary and comparative gastroenterology. This review summarizes the major categories of natural products investigated for colitis, including flavonoids, polyphenols, alkaloids, terpenoids, saponins, polysaccharides, plant extracts, and traditional herbal formulas, and discusses their principal mechanisms of action, such as anti-inflammatory activity, attenuation of oxidative stress, restoration of intestinal barrier integrity, modulation of immune responses, regulation of gut microbiota, and control of programmed cell death. We also highlight the major limitations of current research, including overreliance on preclinical models, insufficient target validation, poor bioavailability, and limited clinical evidence. Overall, natural products represent an important source of therapeutic candidates for colitis, but their clinical translation will require deeper mechanistic studies, standardized evaluation, and well-designed clinical investigations. Importantly, future studies should distinguish phenotype-associated changes from causal mechanisms by integrating direct target engagement, functional rescue experiments, microbiota-causality validation, and standardized pharmacokinetic and safety assessment.