Total alkaloids of Zanthoxylum schinifolium Siebold & Zucc attenuate ulcerative colitis by re-profiling gut microenvironment and inhibiting TLR4/NF-κB pathway

Ulcerative colitis (UC), as a chronic and recurrent inflammatory bowel illness, has become more commonplace worldwide recently. Green Sichuan Pepper ( Zanthoxylum schinifolium Siebold & Zucc, ZS) is a spice and traditional Chinese medicine used millennia in China, total alkaloids of which (TAZS) are important and representative bioactive compounds with multiple pharmacological activities. While, the effects of TAZS on UC have been still unknown. In this study, the effects and the underlying mechanisms of TAZS on UC were investigated. Results showed that TAZS (80 mg/kg·d −1 , i.g.) significantly relieved colitis symptoms and intestinal barrier impairment, inhibited colonic inflammation, and maintained intestinal microenvironment homeostasis. The mechanism of TAZS on UC was through suppressing the abnormal activation of the TLR4/NF-κB pathway, by itself and modulation of gut microenvironment (including intestinal flora and gut microbial metabolites). The present study highlighted the potential of TAZS as a dietary agent for the prevention or treatment of UC. • Intragastric administration of the total alkaloids of Zanthoxylum schinifolium Siebold & Zucc (TAZS) (80 mg/kg·d −1 ) for 6 d alleviated colitis symptoms, attenuated intestinal barrier impairment, and inhibited colonic inflammation in Ulcerative colitis (UC) mice induced by dextran Sulfate Sodium Salt (DSS). • TAZS maintained gut microbiota homeostasis in UC mice. • TAZS re-profiled gut microbiota metabolites in UC mice. • TAZS suppressed the abnormal activation of the TLR4/NF-κB pathway either by itself or by re-profiling gut microenvironment in colon of UC mice. • TAZS could serve as a dietary agent for the prevention or treatment of UC.