Schisandrin protects against ulcerative colitis by inhibiting the SGK1/NLRP3 signaling pathway and reshaping gut microbiota in mice

Abstract

Background According to the Chinese Pharmacopoeia, the fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese medicine that can be used to treat diarrhea. Despite the increasing research on the anti-inflammatory and anti-oxidant aspects of SC, the studies on the anti-ulcerative colitis of Schisandrin (SCH), the main constituent of SC, are relatively few. Methods The mice used in the study were randomly distributed into 6 groups: control, model, 5-ASA, and SCH (20, 40, 80 mg/kg/d). The mice in the model group were administered 3% (w/v) dextran sulfate sodium (DSS) through drinking water for 7 days, and the various parameters of disease activity index (DAI) such as body weight loss, stool consistency, and gross blood were measured. ELISA was used to detect inflammatory factors, and bioinformatics combined with transcriptome analysis was done to screen and verify relevant targets. 16S rDNA high-throughput sequencing was used to analyze the composition of the gut microbiota(GM), while mass spectrometry was done to analyze the changes in the content of bile acids (BAs) in the intestine. Results Mice treated with SCH experienced significant weight gain, effectively alleviating the severity of colitis, and decreasing the levels of inflammatory factors such as TNF-α, IL-1β, IL-18, IL-6, and other related proteins (NLRP3, Caspase-1, SGK1) in UC mice. Furthermore, the analysis of GM and BAs in mice revealed that SCH increased the relative abundance of Lactobacilli spp, reduced the relative abundance of Bacteroides, and promoted the conversion of primary BAs to secondary BAs. These effects contributed to a significant improvement in the DSS-induced GM imbalance and the maintenance of intestinal homeostasis. Conclusion It seems that there is a close relationship between the SCH mechanism and the regulation of SGK1/NLRP3 pathway and the restoration of GM balance. Therefore, it can be concluded that SCH could be a potential drug for the treatment of UC.

Sishen Pill and its active phytochemicals in treating inflammatory bowel disease and colon cancer: an overview

“…The modification and degradation of β -catenin are key events in the occurrence and development of colon cancer ( Zhao et al, 2022 ). The research indicates that Sishen Pills ( Zhao et al, 2019 ) and their active metabolites, schisandrin B ( Zhang et al, 2021a ), schisandrin ( Wang et al, 2023d ), evodiamine ( Kim et al, 2019 ; Shen et al, 2019 ; Ding et al, 2020 ), and rutaecarpine ( Byun et al, 2022 ) could affect cell fate by regulating the NLRP3 and Wnt signaling pathways, thus offering a therapeutic role in IBD and colon cancer.…”

“…For example, schisandrin A ( Wang et al, 2023b ), schisandrin B ( Liu et al, 2015 ), schisandrin C ( Kim et al, 2022 ) and deoxyschizandrin ( Yu and Qian, 2021 ) inhibited the NF-κB nuclear translocation and downstream pro-inflammatory signaling pathway activation; schisandrin B could also regulate AMPK/Nrf2, affect NLRP3 inflammasome, and then alleviate cell pyroptosis and intestinal epithelial damage caused by immune inflammation. In addition, Wang et al conducted a pharmacokinetic analysis of seven different types of lignin in Schisandrae Chinensis and found that C max and AUC 0-∞ of schisandrin were significantly higher than those of other lignans; they also confirmed that it could treat UC by inhibiting the serum/glucocorticoid regulated kinase 1 (SGK1)/NLRP3 pathway and regulating the gut microbiota ( Wang et al, 2023d ).…”

Recent advances in metal-free catalytic enantioselective higher-order cycloadditions

“…These reactions have attracted much attention due to their ability to produce complex polycyclic structures ( e.g. natural products, pharmaceuticals, or valuable intermediates) 11–55 (Scheme 1).…”

Recent progress in the construction of eight-membered nitrogen-heterocycles

“…4 In particular, eight-membered nitrogen-heterocycles are regarded as compelling privileged structures for drug discovery, especially for challenging targets that are difficult to modulate by conventional small molecule screening libraries. 5–8 In general, the installment of nitrogen heteroatoms in a ring system enhances the interaction with a biological target, yielding pharmaceuticals with more potent activities. 9,10 For example, (+)-balasubramide, an eight-membered lactam isolated from Clausena indica exhibits anti-neuroinflammatory properties (Scheme 1A).…”