Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome

Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence in many countries. The purpose of this study is to explore the function of Schisandrin B and its underlying molecular mechanisms in colitis. In this study, mice with colitis were induced by giving 2.0% dextran sulfate sodium (DSS, MP) in the drinking water for seven days. Furthermore, TCMSP server and GEO DataSets were used to analyze the mechanism of Schisandrin B in colitis. It was found that Schisandrin B presented colitis in mice model. At the same time, Schisandrin B not only reduced inflammation in vivo and vitro model of colitis, but also suppressed the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome in vivo and vitro model of colitis. In addition, Schisandrin B induced AMP-activated protein kinase (AMPK) / Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in model of colitis, and regulated AMPK protein at 316 sites. The inhibition of AMPK reduced the anti-inflammation effects of Schisandrin B on NLRP3 inflammasome. Apart from that, Schisandrin B decreased reactive oxygen species (ROS)-induced mitochondrial damage and reduced epithelial cells damage of colitis through regulating pyroptosis. Collectively, our novel findings for first time showed that, Schisandrin B suppressed NLRP3 inflammasome activation-mediated interleukin-1beta (IL-1 beta) level and pyroptosis in intestinal epithelial cells of colitis model through the activation of AMPK/Nrf2 dependent signaling-ROS-induced mitochondrial damage, which may be a significant therapeutic approach in the treatment of acute colitis.

Automated summary

Schisandrin B shows potential as a therapeutic approach for treating ulcerative colitis by reducing inflammation, suppressing NLRP3 inflammasome, inducing the AMPK/Nrf2 signaling pathway, and reducing ROS-induced mitochondrial damage, as demonstrated in mouse models of colitis.