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.

Sinomenine Hydrochloride Ameliorates Fish Foodborne Enteritis via α7nAchR-Mediated Anti-Inflammatory Effect Whilst Altering Microbiota Composition

“…In zebrafish, intestinal macrophages have been reported to have the ability to shape gut microbiota ( 27 ). These are in line with that SN-altered gut microbiota composition when treating DSS-induced colitis ( 17 ).…”

“…When considering effectors, fish SBMIE showed typical allergic cytokine profiles ( 15 ), similar to IBD in humans. For proinflammatory cytokines, TNF-α was highly expressed (especially in the epithelial cells) for accelerating intestinal inflammation ( 16 , 17 ). The acute inflammation-related TNF-α, IL-1β, and allergic cytokine IL-17A/F have also been reported in fish SBMIE ( 4 , 15 , 18 ).…”

“…Sinomenine derivatives have also improved the immunosuppressive activity of its parent natural compound ( 24 ). For SN’s effect on intestinal humoral immunity, sinomenine hydrochloride may suppress proinflammatory cytokines (such as TNF-α) and increase anti-inflammatory cytokine IL-10 during DSS-induced enteritis in mice ( 17 ). At a cellular level, sinomenine could either promote macrophage reprogramming toward M2-like phenotype ( 25 ) or induce the generation of Treg by upregulating the transcriptional factor Foxp3 ( 22 ).…”

Sinomenine Ameliorates Colitis-Associated Cancer by Modulating Lipid Metabolism via Enhancing CPT1A Expression

“…On the one hand, colon tissue is the site of colon cancer. On the other hand, accumulating evidence suggests that the action of SIN is gut-dependent [ 30 , 31 , 32 , 33 ]. Consequently, colonic tissues were selected to investigate the changes of metabolic enzymes of differential metabolites in this study.…”

Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage

“…There is increasing evidence that the NLRP3 inflammasome may be at the crossroads of the brain-gut-microbe connection. The gut microbiota is crucial in the activation of the NLRP3 inflammasome (an important mediator of microbiome-induced inflammatory responses) [10][11][12]. The gut microbiota is a very large group of microorganisms that live in the human gut.…”