Revealing the mechanism of "Huai Hua San" in the treatment of ulcerative colitis based on network pharmacology and experimental study.

ETHNOPHARMACOLOGICAL RELEVANCE: "Huai Hua San" (HHS) is one of the first hundred ancient classic prescriptions drugs, which is commonly used to treat hemorrhoids, colitis, and other symptoms of wind heat in stool. However, the potential molecular mechanism of action of this substance remains unclear. AIMS OF THE STUDY: In this study, we explored the active compounds of HHS for the treatment of ulcerative colitis (UC), predicted the potential targets of the drug, and studied its mechanism of action through network pharmacology via in vitro and in vivo experiments. MATERIALS AND METHODS: First, we identified the active compounds and key targets of HHS for treating UC via network pharmacology. The key signaling pathways associated with the anti-inflammatory effect of HHS were analyzed. The anti-inflammatory effects of HHS and its active compounds were studied using the RAW264.7 inflammatory cell model in vitro. Furthermore, we used the dextran sulfate sodium (DSS) mouse model to explore the efficacy and mechanism of HHS in UC in vivo, and the expression level of key proteins were detected by Western blotting. RESULTS: In all, 23 compounds and 97 targets were obtained from TCMSP database, PharmMapper database, and GeneCards database. After enrichment via Kyoto Encyclopedia of Genes and Genomes (KEGG), HIF-1 signaling pathway, PI3K/AKT signaling pathway, and VEGF signaling pathway were identified to be the top three signaling pathways associated with UC treatment. The results of molecular docking showed that the docking scores of the top 10 active compounds were higher than the threshold values. In vitro, different concentrations of HHS and the four main active compounds could effectively inhibit the release of inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 ß. In vivo, HHS could alleviate UC symptoms. CONCLUSION: Taken together, the treatment of UC with HHS may alleviate the inflammatory response of the colon, and HHS mainly inhibits the EGFR/PI3K/AKT/HIF-1/VEGF signaling pathways.

Network pharmacology and molecular docking reveal the mechanism of Scopoletin against non-small cell lung cancer.

AIMS: Scopoletin is a natural anticarcinogenic and antiviral coumarin component. Many studies have proved its anti-cancer effect, and after the preliminary screening of this study, Scopoletin had the best inhibitory effect on Non-small cell lung cancer (NSCLC). But its mechanism for treating NSCLC is still unclear. Therefore, network pharmacology and molecular docking technology were used to explore the potential anti-NSCLC targets and pathways of Scopoletin. The results were verified in vitro. MAIN METHODS: First, Scopoletin was isolated from Fennel and screened to conduct cell proliferation assay on Human lung cancer cell line A549, Human colon cancer cell line HCT-116 and Human hepatoma cell line HepG2 respectively, through the MTT test. Then, the key targets and related pathways were screened through Protein-protein Interaction (PPI) network and "component-target-pathway" (C-TP) network constructed by network pharmacology. And the key targets were selected to dock with Scopoletin via molecular docking. A549 and Human normal lung epithelial cell BEAS-2B were used to verify the results, finally. KEY FINDINGS: Through MTT, A549 was chosen as the test cancer cell. From network pharmacology, 16 targets, 27 signaling pathways and 16 GO items were obtained (P < 0.05). The results of PPI network and molecular docking showed that EGFR, BRAF and AKT1 were the key targets of Scopoletin against NSCLC, which were consistent with the western-blot results. SIGNIFICANCE: Through network pharmacology, molecular docking and experiments in vitro, Scopoletin was verified to against NSCLC through RAS-RAF-MEK-ERK pathway and PI3K/AKT pathway.