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

Abstract

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-1β) 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.

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

“…Schisandrin B treatment attenuated the vascular injury and fibrosis mediated by the endothelial to mesenchymal transition in vitro and in vivo [ 176 ]. Moreover, schisandrin B reduced epithelial cell injury in a model of colitis by modulating pyroptosis through AMPK/Nrf2/NLRP3 inflammasome pathways [ 177 ] as well as regulated STAT3-dependent Th17 cell differentiation and IL-17A cytokine release [ 178 ].…”

Schisandrin A from Schisandra chinensis Attenuates Ferroptosis and NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy through Mitochondrial Damage by AdipoR1 Ubiquitination

“…For the ROS involved in the activation of the NLRP3 inflammasome, the mitochondrial source is currently more recognized, namely, mitochondrial ROS (mtROS) [33,34]. Studies have confirmed that there is a close correlation between mitochondrial dysfunction and the activation of NLRP3 inflammasome [17]. Under the stimulation of various NLRP3 agonists, mitochondria become dysfunctional, and the production of mtROS increases, which leads to the formation of NLRP3 inflammasomes and the release of inflammatory mediators [35].…”

“…Schisandra chinensis, as a Chinese functional food, is rich in unsaturated fatty acids, minerals, vitamins, and proteins, and used as a tonic and sedative agent in traditional Chinese medicine [14][15][16]. Schisandrin A is one of the lignans isolated from the dried fruits of Schisandra chinensis [17,18]. It has a wide range of pharmacological effects in antioxidation, inhibition of apoptosis, and regulation of immunity [19,20].…”

Decoding the Mechanism of Shen Qi Sha Bai Decoction in Treating Acute Myeloid Leukemia Based on Network Pharmacology and Molecular Docking

“…According to the active components identified based on TCMSP, we performed target fishing using the TCMSP and BATMEN-TCM, obtained a total of 264 potential targets of active components from SQSBD (Zhang et al, 2021). We also used GEO database to obtaine 1,505 differential expression genes (DEGs) of AML.…”