Acanthoside B attenuates NLRP3-mediated pyroptosis and ulcerative colitis through inhibition of tAGE/RAGE pathway

• Xiaobo He ^[1] ; Chunfang Zhou ^[1] ; Rui Shang ^[1] ; Xiaoyan Wang ^[1]
  1. [1] Hubei University of Medicine

     Hubei University of Medicine

     China

     
• Localización: Allergologia et immunopathologia: International journal for clinical and investigate allergology and clinical immunology, ISSN-e 1578-1267, ISSN 0301-0546, Vol. 53, Nº. 1, 2025, págs. 112-122
• Idioma: inglés
• Enlaces
  • Texto completo
• Resumen

  • Acanthoside B (Aca.B), a principal bioactive compound extracted from Pogostemon cablin, exhibits superior anti-inflammatory capacity. Ulcerative colitis is a nonspecific inflammatory bowel disease with unknown etiology. The potential of Aca.B as a therapeutic agent for ulcerative colitis is also unknown and remains an area for future investigation. In this study, we established both in vitro and in vivo models to investigate ulcerative colitis, utilizing Llipopolysaccharide (LPS)-stimulated MODE-K cells and dextran sulfate sodium (DSS)-induced colitis in mice, respectively. The progression of ulcerative colitis was evaluated through histologic analysis, body weight monitoring, and assessment of disease activity index assessment. Furthermore, the effects on pyroptosis were detected through immunoblot analysis. We found that Aca.B treatment significantly ameliorated LPS-induced injury in MODE-K cells, as evidenced by increased cell viability and inhibition of inflammatory response. Moreover, the Aca.B treatment attenuated pyroptosis-specific protein expression, caspase-1 activation, and inflammatory cytokine secretion. In the animal study, Aca.B administration improved bowel symptoms in DSS-induced colitis mice model. This was accompanied by reductionsreduced inweight, colon shortening, inflammatory cell infiltration, and cell pyroptosis in vivo. Furthermore, Aca.B diminished the accumulation of advanced glycation end-products (AGE), resulting in a decrease in the expression of the receptor of AGE (RAGE) and downstream phosphorylated P65 expression. e.The inhibition of the inflammatory response and pyroptosis by Aca.B depends on suppressing the AGE/RAGE pathway. This study confirms the effects of Aca.B on pyroptosis and ulcerative colitis, providing a fundamental evidence for translating Aca.B into clinical applications as an anti-inflammatory medicine.