Network pharmacology-based research on the effect of Scutellaria baicalensis on osteosarcoma and the underlying mechanism.

To explore the anti-tumor effects of Scutellaria baicalensis on osteosarcoma and its mechanism. Network pharmacology and molecular docking techniques were applied to investigate the effect and mechanism of Scutellaria baicalensis on osteosarcoma (OS). We analyzed the protein-protein interaction (PPI) network for potential targets of Scutellaria baicalensis for treating osteosarcoma and identified hub targets. We used KM curves to screen for hub targets that could effectively prolong the survival time of OS patients. We systematically performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of the Scutellaria baicalensis potential targets and predicted the Scutellaria baicalensis molecular mechanism and function in treating osteosarcoma. Through molecular docking, the binding process between the hub targets, which could prolong the survival time of sarcoma patients, and Scutellaria baicalensis was simulated. PPI network analysis of potential therapeutic targets discriminated 12 hub targets. The KM curves of the hub targets showed that upregulation of RXRA, RELA, ESR1, TNF, IL6, IL1B, and RB1 expression, and downregulation of MAPK1, VEGFA, MAPK14, CDK1, and PPARG expression were effective in improving the 5-year survival rate of OS patients. GO and KEGG enrichment demonstrated that Scutellaria baicalensis regulated multiple signaling pathways of OS. Molecular docking results indicated that Scutellaria baicalensis could bind freely to the above hub target, which could prolong the survival time of sarcoma patients. Scutellaria baicalensis acted on osteosarcoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways. Scutellaria baicalensis appears to have the potential to serve as a therapeutic drug for osteosarcoma and to prolong the survival of OS patients.

Compound sophorae decoction enhances intestinal barrier function of dextran sodium sulfate induced colitis via regulating notch signaling pathway in mice.

BACKGROUND: Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. METHODS: In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. RESULTS: CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. CONCLUSIONS: These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.

Uncovering the Anticancer Mechanism of Compound Sophorae Decoction against Ulcerative Colitis-Related Colorectal Cancer in Mice.

Compound sophorae decoction (CSD), a traditional Chinese medicine (TCM) formula, has been voluminously used in China to deal with ulcerative colitis and gained significant therapeutic effect. Tremendous explorations have unraveled a contributory role of inflammatory bowel disease (IBD) like ulcerative colitis (UC) and Crohn's disease (CD) at the onset of colorectal cancer, scilicet, and colitis-related cancer (CRC). In light of the anti-inflammatory properties of CSD in UC, we appraised its chemoprevention capacity and underlying mechanism in ulcerative colitis-related colorectal cancer (UCRCC), employing a model of azoxymethane (AOM) plus dextran sulfate sodium- (DSS-) induced colorectal cancer (CRC) in C57BL/6 mice. Rapturously, our results illuminated the ameliorative effect of CSD against UCRCC in mice portrayed by lesser polyps or adenomas, attenuated colonic xenograft tumor growth in company with the preferable well-being of mice in contrast to the Model Group. We examined significant downregulation of proinflammatory cytokines such as TNF-α, NF-κB, IL-6, STAT3, and IL-17 after exposure to CSD, with the concomitant repression of inflammation-associated proteins, including COX-2 and iNOS. Independent of this, treatment with CSD declined the proportion of T helper 17 cells (Th17) and protein level of matrix metallopeptidase 9 (MMP-9). Moreover, transmission electron microscopy (TEM) detected observably suppressed mitophagy in mice administered with CSD and that was paralleled by the pro-apoptotic effect as indicated by upregulating caspase-3 together with caspase-9 and deregulating B-cell lymphoma 2 (Bcl-2). In closing, these findings suggest CSD executes the UCRCC-inhibitory activity through counteracting inflammatory responses and rescuing detuning of apoptosis as well as neutralizing overactive mitophagy, concurring to build up an oncosuppressive microenvironment.

Effect of compound sophorae decoction on dextran sodium sulfate (DSS)-induced colitis in mice by regulating Th17/Treg cell balance.

OBJECTIVE: Compound sophorae decoction, a Chinese medicinal formulae composed of six Chinese herbs, is effective for the clinical treatment of ulcerative colitis (UC). Some of its effective monomers had been proven to have suppressive effect on UC models. The aim of this study is to further explore the mechanism whether compound sophorae decoction ameliorates dextran sodium sulfate (DSS)-induced mice colitis by regulating the balance between T helper (Th) 17 and regulatory T (Treg) cells. METHODS: Experimental model of UC, established by drinking water with DSS, was treated with compound sophorae decoction and mesalazine. The stool, activity, body weight of the mice, colon length and colon histopathology were observed to evaluate severity of colitis. The concentration of cytokines in colonic tissues were detected by ELISA. The expression of phosphorylated nuclear factor-kappaB (NF-κB) p65, STAT3 and phosphorylated STAT3 in colonic tissues were determined by western blotting and immunohistochemistry. The percentage of Th17 and Treg cells in spleen and mesenteric lymph nodes (MLNs) were detected by flow cytometry. The levels of transcription factor ROR-γt and FOXP3 in colon tissues were detected by qRT-PCR and immunohistochemistry. RESULTS: The aqueous extract of compound sophorae decoction was able to improve the symptoms and pathological damage of mice. The body weight of mice were increased and DAI were significantly decreased; ulcers were slighter than DSS group. The administration of compound sophorae decoction reduced the level of inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and phospho-NF-κB p65, and also decreased the proportions of Th17 cells in spleen and MLNs and the expression of ROR-γt, IL-17A, STAT3, IL-6 in colonic tissues; while the percentage of Treg cells in spleen and MLNs and the expression of FOXP3, transforming growth factor (TGF)-ß1, IL-10 in colonic tissues were upregulated. CONCLUSION: Overall, this study suggested that compound sophorae decoction significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.