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 ... -  《-》

Using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry, network pharmacology, and molecular docking to explore the constituent targets and action mechanisms of decoction of Angelica sinensis, Zing

Liu Z ，Zheng Z ，Wang T ，Liu Z ，Zuo Z ... -  《-》

Network pharmacology and molecular docking reveal the immunomodulatory mechanism of rhubarb peony decoction for the treatment of ulcerative colitis and irritable bowel syndrome.

Background: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) share various similarities in clinical symptoms, pathogenesis, and treatment. UC concurrent IBS tends toward more severe symptoms and worse prognosis, and promising feasible therapies for the overlapping symptoms remains a challenge. Rhubarb peony decoction (RPD) is a well-known traditional Chinese medicine that has been widely applied in treating UC. RPD may exert extensive therapeutic effects on both IBS and UC. However, the common mechanism of its treatment remains unclear. We aimed to assess the potential pharmacological mechanism of RPD in the treatment of overlapping IBS and UC. Methods: The active components and targets of RPD were retrieved from ETCM, TCMSP, BATMAN-TCM, and TCM databases. The disease targets were screened by searching the DrugBank, OMIM, TTD, and PharmGKB databases. PPI network analysis was performed and visualized via the STRING platform and Cytoscape software. GO and KEGG enrichment analyses of the hub genes of RPD were predicted to elucidate the potential molecular mechanism. Subsequently, molecular docking was carried out to verify the combination of active compounds with core targets. Results: By integrating all targets of RPD and disease, a total of 31 bioactive ingredients were identified including quercetin, kaempferol, aloe-emodin, beta-sitosterol, and (+)-catechin, etc. JUN, TP53, MAPK1, RELA, MYC, and ESR1 were explored as potential therapeutic targets among 126 common drug-disease-related targets. They were enriched in the AGE-RAGE signaling pathway in diabetic complications, as well as the NF-kappa B signaling pathway and MAPK signaling pathway. Additionally, some active ingredients were identified as candidates for binding to the hub targets via molecular docking, further suggesting their anti-inflammatory and antioxidative properties. Conclusion: RPD may exert the overall treatment effect for UC and IBS overlap syndrome via the biological mechanism of "multi-ingredients, multi-targets, and multi-pathways" on inflammation, oxidative stress, immune, oncogenicity, and gut microbiota dysbiosis.

Zhai L ，Yang W ，Li D ，Zhou W ，Cui M ，Yao P ... -  《JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES》

Research on the Regulatory Mechanism of Ginseng on the Tumor Microenvironment of Colorectal Cancer based on Network Pharmacology and Bioinformatics Validation.

A network pharmacology study on the biological action of ginseng in the treatment of colorectal cancer (CRC) by regulating the tumor microenvironment (TME). To investigate the potential mechanism of action of ginseng in the treatment of CRC by regulating TME. This research employed network pharmacology, molecular docking techniques, and bioinformatics validation. Firstly, the active ingredients and the corresponding targets of ginseng were retrieved using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Traditional Chinese Medicine Integrated Database (TCMID), and the Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan). Secondly, the targets related to CRC were retrieved using Genecards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM). Tertiary, the targets related to TME were derived from screening the GeneCards and National Center for Biotechnology Information (NCBI)-Gene. Then the common targets of ginseng, CRC, and TME were obtained by Venn diagram. Afterward, the Protein-protein interaction (PPI) network was constructed in the STRING 11.5 database, intersecting targets identified by PPI analysis were introduced into Cytoscape 3.8.2 software cytoHubba plugin, and the final determination of core targets was based on degree value. The OmicShare Tools platform was used to analyze the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets. Autodock and PyMOL were used for molecular docking verification and visual data analysis of docking results. Finally, we verified the core targets by Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases in bioinformatics. A total of 22 active ingredients and 202 targets were identified to be closely related to the TME of CRC. PPI network mapping identified SRC, STAT3, PIK3R1, HSP90AA1, and AKT1 as possible core targets. Go enrichment analysis showed that it was mainly involved in T cell co-stimulation, lymphocyte co-stimulation, growth hormone response, protein input, and other biological processes; KEGG pathway analysis found 123 related signal pathways, including EGFR tyrosine kinase inhibitor resistance, chemokine signaling pathway, VEGF signaling pathway, ErbB signaling pathway, PD-L1 expression and PD-1 checkpoint pathway in cancer, etc. The molecular docking results showed that the main chemical components of ginseng have a stable binding activity to the core targets. The results of the GEPIA database showed that the mRNA levels of PIK3R1 were significantly lowly expressed and HSP90AA1 was significantly highly expressed in CRC tissues. Analysis of the relationship between core target mRNA levels and the pathological stage of CRC showed that the levels of SRC changed significantly with the pathological stage. The HPA database results showed that the expression levels of SRC were increased in CRC tissues, while the expression of STAT3, PIK3R1, HSP90AA1, and AKT1 were decreased in CRC tissues. Ginseng may act on SRC, STAT3, PIK3R1, HSP90AA1, and AKT1 to regulate T cell costimulation, lymphocyte costimulation, growth hormone response, protein input as a molecular mechanism regulating TME for CRC. It reflects the multi-target and multi-pathway role of ginseng in modulating TME for CRC, which provides new ideas to further reveal its pharmacological basis, mechanism of action and new drug design and development.

Wang T ，Zhang W ，Fang C ，Wang N ，Zhuang Y ，Gao S ... -  《-》

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 ... -  《-》