Moxibustion attenuates inflammation in intestinal mucosal by regulating RAGE-mediated TLR4-NF-κBp65 signaling pathway in vivo and in vitro.

This study was performed to investigate the effect of moxibustion on the RAGE/TLR4-NF-κBp65 pathways and mucosal damage in rat model of 5-fluorouracil (5-Fu)-induced intestinal mucositis (IM) and the underlying mechanisms. 5-Fu treatment significantly increased the expression of the receptor for advanced glycation end products (RAGE) and its ligand, thehigh-mobility group box 1 protein (HMGB1), in the rat intestinal tissue. The inhibition of RAGE could induce the repair of intestinal mucosal damage and downregulate the expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-B (NF-κB) p65 in intestinal tissues of 5-Fu-treated rats. Moxibustion treatment significantly improved the physical symptoms and repaired the intestinal mucosal damage of IM rats and increased the expression of tight junction proteins in these rats. The expression of RAGE, HMGB1, TLR4, NF-κBp65, and related downstream inflammatory factors, namely, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, were significantly decreased after moxibustion treatment. A moxibustion dose of 15 min/day exerted a better therapeutic effect than a dose of 30 min/day. The phosphorylation of NF-κBp65 and IκBa is involved in reducing inflammation by regulating the RAGE signaling pathway. Moxibustion can reduce intestinal mucosal damage and inflammation in 5-Fu-induced IM rats via modulation of the RAGE/TLR4-NF-κBp65 signaling pathways. AJTR