Sinomenine hydrochloride ameliorates dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota composition whilst suppressing the activation of the NLRP3 inflammasome

Abstract

Sinomenine is a pure alkaloid that can be isolated from the root of Sinomenium acutum and has been found to exert anti-inflammatory and immunosuppressive effects. The present study investigated the effects of sinomenine hydrochloride (SIN) on inflammation and the gut microbiota composition in the colon of mouse models of dextran sulfate sodium (DSS)-induced colitis. DSS-induced mice colitis was established by treating the mice with drinking water containing 3% (w/v) DSS for 7 days. The disease activity index of each mouse was calculated on a daily basis. All mice were sacrificed on day 11, then the weight of their spleen and length of their colons were measured. The histological analysis was measured by hematoxylin-eosin staining. Oral administration of SIN (100 mg/kg/day) attenuated the DSS-induced increases in the disease activity indices and spleen indices, DSS-induced shortening of the colon length and histological damage. In addition, reverse transcription-quantitative PCR data showed that SIN treatment effectively regulated the expression of inflammatory mediators, specifically by suppressing the expression of proinflammatory gene (TNF-α, IL-6 and inducible nitric oxide synthase) whilst increasing those associated with inhibiting inflammation (IL-10 and arginine 1). Gut microbiota analysis was conducted using 16S ribosomal DNA sequencing. The results revealed that SIN improved bacterial community homeostasis and diversity, which were damaged by DSS. Furthermore, western blotting showed that the activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome was markedly suppressed by SIN treatment. In conclusion, these results indicated that SIN may ameliorate experimental colitis by modulating the gut microbiota composition and suppressing the activation of the NLRP3 inflammasome in mice. Overall, these findings suggested a broad protective effect of SIN in treating inflammatory gut diseases, including ulcerative colitis.

Keywords: LRR- and pyrin domain-containing protein 3 inflammasome; NOD-; Sinomenine hydrochloride; dextran sulfate sodium-induced colitis; gut microbiota composition; ulcerative colitis.