Herbal Enema Formula Ameliorates Dextran Sodium Sulfate-Induced Colitis by Modulating NLRP3/SIRT6 Signaling Pathway
[Objective]To investigate the protective effect of herbal enema formula on dextran sodium sulfate(DSS)-induced ulcerative colitis (UC) and its mechanism of action.[Methods]C57BL/6J mice were given 2.5％ DSS aqueous solution for 7 d to induce UC.After 2 d,mice in herbal enema formula low,medium and high dose groups were given 1.3 g/kg,2.6 g/kg and 5.2 g/kg herbal enema formula for edema;0.2 g/kg sulfasalazine were given to positive control group for enema;mice in model group and normal group were given equal volumes of 0.9％ sodium chloride solution for enema,respectively.The degree of lesions was observed by hematoxylin-eosin(HE) staining in mice colon tissue sections;serum inflammatory factor tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β) and interleukin-18(IL-18) were determined by enzyme linked immunosorbent assay(ELISA);myeloperoxidase(MPO) and superoxide dismutase (SOD) activities,nitric oxide(NO) and malondialdehyde(MDA) levels were detected by physiological and biochemical assay kits;protein expression levels of zonula occludens protein-1(ZO-1),occludin,nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3),and sirtuin 6(SIRT6) in mouse colon tissues were detected by western blot.[Results]Compared with normal group,DSS induced colonic inflammation,crypt loss,cuprocyte depletion and inflammatory infiltration;serum TNF-α,IL-6,IL-1β,and IL-18 inflammatory factor levels,MPO activity,NO and MDA levels were significantly increased(P<0.01,P<0.001),and SOD activity was significantly decreased(P<0.01).After treatment,the herbal enema formula significantly improved the DSS-induced colonic inflammation of crypt loss,cuprocyte depletion,and inflammatory infiltration.The levels of serum TNF-α,IL-6,IL-1β and IL-18 inflammatory factors,MPO activity and NO and MDA levels were significantly decreased(P<0.01,P<0.001),and SOD activity were significantly increased in medium dose and high dose groups(P<0.05).The protein expression levels of ZO-1,occludin and SIRT6 in the colonic tissues of mice in herbal enema formula group were significantly higher(P<0.001,P<0.01,P<0.05),and the protein expression levels of NLRP3 in medium dose and high dose groups were significantly lower(P<0.01).[Conclusion]The herbal enema formula has a protective effect against DSS-induced UC,and its mechanism includes alleviating inflammation,reducing oxidative stress,improving intestinal barrier permeability,and regulating the NLRP3/SIRT6 signaling pathway.
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