The potential mechanism of Bletilla striata in the treatment of ulcerative colitis determined through network pharmacology, molecular docking, and in vivo experimental verification.
Ulcerative colitis (UC) is a chronic nonspecific intestinal inflammatory disease, which belongs to a subtype of inflammatory bowel disease, but still lacks effective drug treatment. Bletilla striata (B. striata) is one of the most valuable traditional Chinese medicines (TCMs) in China, can stop bleeding, can promote wound healing, and can regulate immunity. Based on data mining, B. striata was found to be a common TCM for the treatment of UC, but the exact therapeutic mechanism is not yet known. This study aims to explore the potential mechanisms of B. striata in the treatment of UC using network pharmacology, molecular docking techniques, and in vivo experimental research. We extracted the active ingredients and targets of B. striata from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform. We retrieved and screened the corresponding UC-related target genes in multiple databases. Subsequently, we constructed an herb-ingredient-target-disease-network, generated a protein-protein interaction network, performed Gene Ontology enrichment analysis, and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify potential treatment mechanisms. After screening for key active ingredients and target genes, we performed molecular docking using AutoDock Vina software to select the best binding target for molecular docking and validate the binding activity. The UC model was established in mice, and the results of network pharmacology and molecular docking were verified by in vivo experiments. In all, 5 compounds were obtained from the TCMSP database, and 74 UC-related pathogenic genes were obtained from GeneCards, DisGeNET, OMIM, TTD, and DrugBank. After KEGG enrichment analysis, pathways in cancer, the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway, and metabolic pathways were identified as the top three signalling pathways associated with UC treatment. The results of molecular docking showed that the active components of B. striata have good binding activities to the pivotal targets epidermal growth factor receptor (EGFR) and PIK3CA. In a dextran sulphate sodium-induced colitis model, we found that B. striata can alleviate the symptoms of UC, decrease the secretion of the inflammatory cytokines interleukin-6 and tumour necrosis factor-α, and downregulate the expression levels of EGFR, PIK3CA, and p-AKT. In conclusion, the treatment of UC with B. striata may alleviate the inflammatory response of the colon, and B. striata mainly inhibits the EGFR/PI3K/AKT signalling pathways.
Gong S
，Lv R
，Fan Y
，Shi Y
，Zhang M
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Exploring the Mechanisms of Self-made Kuiyu Pingchang Recipe for the Treatment of Ulcerative Colitis and Irritable Bowel Syndrome using a Network Pharmacology-based Approach and Molecular Docking.
Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are common intestinal diseases. According to the clinical experience and curative effect, the authors formulated Kuiyu Pingchang Decoction (KYPCD) comprised of Paeoniae radix alba, Aurantii Fructus, Herba euphorbiae humifusae, Lasiosphaera seu Calvatia, Angelicae sinensis radix, Panax ginseng C.A. Mey., Platycodon grandiforus and Allium azureum Ledeb.
The aim of the present study was to explore the mechanisms of KYPCD in the treatment of UC and IBS following the Traditional Chinese Medicine (TCM) theory of "Treating different diseases with the same treatment".
The chemical ingredients and targets of KYPCD were obtained using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform (TCMSP). The targets of UC and IBS were extracted using the DisGeNET, GeneCards, DrugBANK, OMIM and TTD databases. The "TCM-component-target" network and the "TCM-shared target-disease" network were imaged using Cytoscape software. The protein-protein interaction (PPI) network was built using the STRING database. The DAVID platform was used to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Using Autodock Tools software, the main active components of KYPCD were molecularly docked with their targets and visualized using PyMOL.
A total of 46 active ingredients of KYPCD corresponding to 243 potential targets, 1,565 targets of UC and 1,062 targets of IBS, and 70 targets among active ingredients and two diseases were screened. Core targets in the PPI network included IL6, TNF, AKT1, IL1B, TP53, EGFR and VEGFA. GO and KEGG enrichment analysis demonstrated 563 biological processes, 48 cellular components, 82 molecular functions and 144 signaling pathways. KEGG enrichment results revealed that the regulated pathways were mainly related to the PI3K-AKT, MAPK, HIF-1 and IL-17 pathways. The results of molecular docking analysis indicated that the core active ingredients of KYPCD had optimal binding activity to their corresponding targets.
KYPCD may use IL6, TNF, AKT1, IL1B, TP53, EGFR and VEGFA as the key targets to achieve the treatment of UC and IBS through the PI3K-AKT, MAPK, HIF-1 and IL-17 pathways.
Wen Y
，Wang X
，Si K
，Xu L
，Huang S
，Zhan Y
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Mechanism of Bazhen decoction in the treatment of colorectal cancer based on network pharmacology, molecular docking, and experimental validation.
Bazhen Decoction (BZD) is a common adjuvant therapy drug for colorectal cancer (CRC), although its anti-tumor mechanism is unknown. This study aims to explore the core components, key targets, and potential mechanisms of BZD treatment for CRC.
The Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to acquire the BZD's active ingredient and targets. Meanwhile, the Drugbank, Therapeutic Target Database (TTD), DisGeNET, and GeneCards databases were used to retrieve pertinent targets for CRC. The Venn plot was used to obtain intersection targets. Cytoscape software was used to construct an "herb-ingredient-target" network and identify core targets. GO and KEGG pathway enrichment analyses were conducted using R language software. Molecular docking of key ingredients and core targets of drugs was accomplished using PyMol and Autodock Vina software. Cell and animal research confirmed Bazhen Decoction efficacy and mechanism in treating colorectal cancer.
BZD comprises 173 effective active ingredients. Using four databases, 761 targets related to CRC were identified. The intersection of BZD and CRC yielded 98 targets, which were utilized to construct the "herb-ingredient-target" network. The four key effector components with the most targets were quercetin, kaempferol, licochalcone A, and naringenin. Protein-protein interaction (PPI) analysis revealed that the core targets of BZD in treating CRC were AKT1, MYC, CASP3, ESR1, EGFR, HIF-1A, VEGFR, JUN, INS, and STAT3. The findings from molecular docking suggest that the core ingredient exhibits favorable binding potential with the core target. Furthermore, the GO and KEGG enrichment analysis demonstrates that BZD can modulate multiple signaling pathways related to CRC, like the T cell receptor, PI3K-Akt, apoptosis, P53, and VEGF signaling pathway. In vitro, studies have shown that BZD dose-dependently inhibits colon cancer cell growth and invasion and promotes apoptosis. Animal experiments have shown that BZD treatment can reverse abnormal expression of PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53 genes. BZD also increases the ratio of CD4+ T cells to CD8+ T cells in the spleen and tumor tissues, boosting IFN-γ expression, essential for anti-tumor immunity. Furthermore, BZD has the potential to downregulate the PD-1 expression on T cell surfaces, indicating its ability to effectively restore T cell function by inhibiting immune checkpoints. The results of HE staining suggest that BZD exhibits favorable safety profiles.
BZD treats CRC through multiple components, targets, and metabolic pathways. BZD can reverse the abnormal expression of genes such as PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53, and suppresses the progression of colorectal cancer by regulating signaling pathways such as PI3K-AKT, P53, and VEGF. Furthermore, BZD can increase the number of T cells and promote T cell activation in tumor-bearing mice, enhancing the immune function against colorectal cancer. Among them, quercetin, kaempferol, licochalcone A, naringenin, and formaronetin are more highly predictive components related to the T cell activation in colorectal cancer mice. This study is of great significance for the development of novel anti-cancer drugs. It highlights the importance of network pharmacology-based approaches in studying complex traditional Chinese medicine formulations.
Lu S
，Sun X
，Zhou Z
，Tang H
，Xiao R
，Lv Q
，Wang B
，Qu J
，Yu J
，Sun F
，Deng Z
，Tian Y
，Li C
，Yang Z
，Yang P
，Rao B
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《Frontiers in Immunology》
Revealing the mechanism of "Huai Hua San" in the treatment of ulcerative colitis based on network pharmacology and experimental study.
"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.
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.
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.
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 β. In vivo, HHS could alleviate UC symptoms.
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.
Chen PY
，Yuan C
，Hong ZC
，Zhang Y
，Ke XG
，Yu B
，Wang C
，Xiao XC
，Wu HZ
，Yang YF
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ResearchGate
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