Schisandrin B prevents ulcerative colitis and colitis-associated-cancer by activating focal adhesion kinase and influence on gut microbiota in an in vivo and in vitro model

et al. 2022

IJMS

Aiming at assessing the therapeutic effect of ethyl rosmarinate (ER) on ulcerative colitis (UC), the following activities were performed in vitro and in vivo in the present study. Firstly, a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was established to determine the level of inflammatory factors. Then, a UC mice model induced by dextran sodium sulfate (DSS) was established to further investigate the effects of ER on symptoms, inflammatory factors and colon histopathology. Finally, serum and colon metabolomics studies were performed to identify the biomarkers and metabolisms closely related to the protective effect of ER on UC. The results showed that after ER intervention, the levels of inflammatory factors (NO, TNF-α, IL-1β and IL-6) and key enzyme (MPO) in cell supernatant, serum or colon were significantly decreased, and the disease activity index and colon tissue damage in mice were also effectively improved or restored. In addition, 28 biomarkers and 6 metabolisms were found to be re-regulated by ER in the UC model mice . Therefore, it could be concluded that ER could effectively ameliorate the progression of UC and could be used as a new natural agent for the treatment of UC.

Section: Discussionmentioning

confidence: 99%

Protective Effect of Ethyl Rosmarinate against Ulcerative Colitis in Mice Based on Untargeted Metabolomics

Zhou

Liu

et al. 2022

IJMS

“…In this study, we found that Schisandrin B presented colitis and reduced inflammation in vivo and vitro model of colitis. Li et al revealed Schisandrin B prevents ulcerative colitis via gut microbiota in an in vivo and in vitro model [ 42 ]. Importantly, we identified that Schisandrin B may be a possible drug for the treatment of colitis.…”

Section: Discussionmentioning

confidence: 99%

“…We found that Schisandrin B suppressed NLRP3 inflammasone in vivo and vitro model of colitis. Chen et al showed that Schisandrin B attenuates inflammation in asthma by inhibiting NLRP3 inflammasome activation [ 42 ]. Thus, our findings showed that NLRP3 inflammasone, a target spot of Schisandrin B on colitis to reduce inflammation factor of intestinal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Shen

et al. 2021

Aging

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.

“…It has been found that the low expression of miR-4728-3p in ulcerative colitis-associated colorectal cancer can act on the CAV1, THBS2, and COL1A2 gene on focal adhesion signaling, which is related to the pathogenesis of the tumor (20). Li J and Wang D found that activation of adhesion macular kinase prevented the development of ulcerative colitis and colitis associated tumors (21). PPI network analysis was further performed on DEGs.…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes and Pathways in Colitis-Associated Colon Cancer by Integrated Bioinformatic Analysis

Yao

Liu

et al. 2021

Preprint

Background Colon cancer is the third leading cause of death in the world. According to the etiology, colon cancer can be divided into three categories: sporadic, hereditary, and colitis-associated colon cancer(CAC). In terms of clinical features, CAC patients have younger age of onset, more multiple lesions, more difficult to find under endoscope, stronger tumor invasiveness than sporadic colorectal cancer patients. Early detection of CAC by endoscopic monitoring is a challenge, and the incidence of septal colorectal cancer is still high. So it is indispensable to find the biomarkers to predict tumorigenesis of CAC. Methods The gene expression profiles of GSE43338 and GSE4904 were downloaded from Gene Expression Omnibus (GEO) database. The Limma package was used to standardize the data and obtain differentially expressed genes (DEGs). Protein-protein interaction (PPI) network was evaluated by STRING database. The Cytoscape software was used to establish PPI network and to perform modular analysis. Functional annotation analysis were performed by the DAVID. The transcription factor (TF) and miRNAs that regulate genes expression were analyzed by using the Network Analyst algorithm. Expression correlation analysis were conducted in GEPIA. The prognostic analysis of hub genes were conducted based on TCGA samples. Results A total of 275 DEGs including 103 up-regulated genes and 172 down-regulated genes were identified by bioinformatics analysis in CAC. IGF1, BMP4, SPP1, APOB, CCND1, CD44, PTGS2, CFTR, BMP2, KLF4, TLR2 were identified as hub DEGs, which were significantly enriched in PI3K-Akt signaling pathway, stem cell pluripotency regulation pathway, Focal adhesion-Hippo signal pathway and AMPK signal pathway respectively. The FOXC1 were crucial regulators for these hub gene according to the TF analysis. The Sankey diagram showed that both PI3K-AKT signal pathway and Focal adhesion were composed of up-regulated genes, such as SPP1, CD44, TLR2, CCND1, IGF1, which were related to core miRNAs, hsa-mir-16-5p, hsa-mir-129-2-3p and hsa-mir-37a-3p by research and prediction. Survival analysis showed that the differential expression of SPP1, CFRT and KLF4 was significantly related to the poor prognosis of CAC. Conclusion This study provided a novel way to illuminate the mechanism of colitis-associated colon cancer. The most of all, the hub genes and signaling pathways may contribute to the prevention, diagnosis and treatment of CAC.