Changji'an Formula (CJAF) is a Chinese herbal compound, which is effective against irritable bowel syndrome with predominant diarrhea (IBS-D) in clinic. However, the molecular mechanism has not been well defined. In the current study, the potential targets and signaling pathways of CJAF against IBS-D were predicted using network pharmacology analysis. The pharmacological mechanisms of CJAF against IBS-D and the potential mechanism were validated by using an IBS-D mouse model induced by enema with trinitrobenzene-sulfonic acid (TNBS) plus with restraint stress and further intervened with CJAF. A total of 232 active compounds of CJAF were obtained, a total of 397 potential targets for the active ingredients were retrieved and a total of 219 common targets were obtained as the potential targets of CJAF against IBS-D. GO and KEGG enrichment analyses showed that multiple targets were enriched and could be experimentally validated in a mouse model of IBS-D. The mechanisms were mainly converged on the immune and inflammatory pathways, especially the NF-κB, TNF and IL-17 signaling pathway, which were closely involved in the treatment of CJAF against IBS-D. Animal experiment showed that CJAF alleviated visceral hypersensitivity and diarrhea symptom of IBS-D. CJAF also restored the histological and ultrastructure damage of IBS-D. The result of Western blot showed that CJAF upregulated colonic tight junction proteins of ZO-1, Occludin and Claudin-1. Further results demonstrated that CJAF inhibited the protein expression of NF-κB/NLRP3 inflammasome pathway targets and downregulated proinflammatory mediators of IL-1β, IL-18, TNF-α. In conclusion, CJAF could effectively reduce inflammatory response and alleviate visceral hypersensitivity as well as diarrhea symptom of IBS-D by inhibiting the NF-κB/NLRP3 signaling pathway. This study not only reveals the mechanism of CJAF against IBS-D, but also provides a novel therapeutic strategy for IBS-D.

Chinese herbal medicine (CHM) is widely used for ulcerative colitis (UC), but product heterogeneity, variable trial quality, and limited long-term safety data preclude class-level efficacy claims. This critical narrative review therefore evaluates evidence at the level of the defined botanical drug product, formulation, route, dose, and manufacturing process. The review focuses on traditional formulas, processed botanical drugs, and proprietary preparations with documented use in Chinese medical practice. Purified plant metabolites such as curcumin and common flavonoids are not treated as uniquely Chinese interventions; they are discussed only when they are part of a defined CHM-related product or when pivotal natural-product trials provide a relevant product-level comparator. Primary randomized trials show heterogeneous results: higher-dose curcumin trials and the curcumin-QingDai combination provide signals of benefit, low-dose curcumin was negative, and indigo naturalis shows dose-related efficacy accompanied by important safety concerns. Mechanistically, the strongest evidence comes from human target engagement or causal perturbation, exemplified by mucosal CYP1A1 induction with curcumin-QingDai and loss of indigo naturalis efficacy in Ahr-deficient mice. Most other mechanistic claims remain preclinical and model-dependent. Translation requires taxonomically authenticated and chemically characterized products, measured exposure, causal mechanism testing, objective CORE-IBD/STRIDE-II-aligned outcomes, CONSORT-CHM reporting, and prospective, batch-traceable pharmacovigilance. No molecular, microbial, or traditional-pattern biomarker has yet shown a prospectively validated treatment-by-biomarker interaction for a defined CHM product. Precision translation should therefore be regarded as a prospective research program rather than an achieved clinical state.