Cluster 1 comprised nine nodes and 33 edges with a score of 8.250 (Figure 3B). asthma primarily through regulation of the IL-4 and IL-13 signaling and the specialized pro-resolving mediators (SPMs) biosynthesis. Molecular docking results suggest that each bioactive compounds (quercetin, wogonin, luteolin, naringenin, and kaempferol) is definitely capable to bind with STAT3, PTGS2, JUN, VEGFA, EGFR, and ALOX5. Summary This study revealed the active ingredients and potential molecular mechanism by which MGMD treatment is effective against airway swelling and redesigning in asthma through regulating IL-4 and IL-13 signaling and SPMs biosynthesis. value corrected from the false discovery rate (FDR) algorithm for each term. Network Building To demonstrate the multi-compound restorative features of MGMD, network constructions were performed as follows: (1) herb-compound-target Network (H-C-T network) was constructed to explore the active compounds and their potential focuses on. The core compounds were acquired through the H-C-T network. (2) PPI networks were built to analyze the prospective interactions. Hub focuses on involved in MGMD treatment of asthma were selected from your PPI network. (3) BP sub-networks were founded for classification analysis of BPs in MGMD treatment for asthma. (4) Target pathway network (T-P network) was constructed to show the practical pathways of MGMD for the therapy of asthma. Molecular Docking Molecular docking was carried out to validate if MGMDs compounds could bind to these focuses on. The 2D constructions of the top five core compounds were downloaded from your TCMSP database (Ru et al., 2014). The constructions were added charge and displayed rotatable secrets by AutoDock Tools (version 1.5.6). The protein crystal structures related to the core target genes were downloaded from your Protein Data Lender database (PDB)14 (Burley et al., 2017). Water and hetero molecules of the proteins were eliminated by Pymol. Hydrogen atoms and charge procedures to the proteins was added by AutoDock Tools. The 3D Grid package for molecular docking simulation was also acquired by AutoDock tools was displayed by AutoDock Vina (version 1.1.2) (Trott and Olson, 2010). The results were analyzed and interpreted by PyMOL and Finding Studio 2020. Results Building of Herb-Compound-Target Network With this study, 96 active compounds were screened from your six natural herbs in MGMD. Among them, 51, 19, 7, 6, 8, and 5 compounds were from FF, QH, JG, WM, WWZ, and YCH, respectively. MGMD consists of a complex mixture of ingredients, some of them overlapped across 2 natural herbs, including decursinol, deoxygomisin A, nodakenetin, and naringenin. A total of 92 active compounds were identified after removing redundant entries. Five hundred and twenty-three focuses on were associated with the 92 parts recognized in MGMD, of which 149 were associated with FF, 151 with QH, 83 with JG, 77 with WM, 23 with WWZ, and 40 with YCH. After removing overlapping focuses on, there were 281 focuses on remaining. The H-C-T network of MGMD was visualized in Cytoscape (Number 2). The network contained 379 nodes and 1021 edges. Quercetin showed the highest degree of connectivity in the network with 76 focuses on, followed by wogonin with 57, luteolin with 55, naringenin with 51, and kaempferol with 40. The properties of the H-C-T network were suitable for showing complex elements, multiple focuses on, and close relationships between elements and focuses on. Detailed information about the active compounds and focuses on recognized in MGMD is definitely demonstrated in Supplementary Table 1. Open in a separate window Number 2 Herb-Compound-Target network (H-C-T network) of MGMD. Green ellipses represent the natural herbs present in MGMD; pink gemstones represent active compounds in each plant; purple gemstones represent active compounds shared by two natural herbs, and blue triangles correspond to related focuses on (The IDs of the parts are explained in Supplementary Table 1). Potential Asthma Focuses on The focuses on for asthma were integrated from multi-source databases and a final list of 1,070 disease-related focuses on obtained after removing duplicates (Supplementary Table 2). 72 overlapping focuses on were identified as the key focuses on for studying the anti-asthmatic activity of the MGMD compounds (Supplementary Table 3). Analysis of the Network of Overlapping Focuses on ProteinCProtein Connection (PPI) Network The STRING database was used to acquire PPI associations of 72 potential protein focuses on of MGMD as related to the treatment of asthma. The visualized PPI network was constructed by Cystoscape 3.7.1,.The pathways result was intensively enriched in SPMs biosynthesis and inflammatory and immune response, including arachidonic acid rate of metabolism, rate of metabolism of lipids, biosynthesis of EPA-derived SPMs, biosynthesis of DHA-derived SPMs, biosynthesis of DPAn-3 SPMs, interleukin-4 and interleukin-13 signaling, and signaling by interleukins and immune system. Open in a separate window FIGURE 5 Results of the pathway analysis of the top 16 pathways: Bubble diagram of pathway (A) and T-P network diagram (B). TABLE 1 Info on enrichment analysis based on Reactome. (Wang et al., 2021). to investigate interactions between active compounds and potential focuses on. Results A total of 92 active compounds and 72 anti-asthma focuses on of MGMD were selected for analysis. The GO enrichment analysis results indicated the anti-asthmatic focuses on of MGMD primarily participate in inflammatory and in airway remolding processes. The Reactome pathway analysis showed that MGMD helps prevent asthma primarily through regulation of the IL-4 and IL-13 signaling and the specialized pro-resolving mediators (SPMs) biosynthesis. Molecular docking results suggest that each bioactive compounds (quercetin, wogonin, luteolin, naringenin, and kaempferol) is definitely capable to bind with STAT3, PTGS2, JUN, VEGFA, EGFR, and ALOX5. Summary This study revealed the active ingredients and potential molecular mechanism by which MGMD treatment is effective against airway inflammation and remodeling in asthma through regulating IL-4 and IL-13 signaling and SPMs biosynthesis. value corrected by the false discovery rate (FDR) algorithm for each term. Network Construction To demonstrate the multi-compound therapeutic features of MGMD, network constructions were performed as follows: (1) herb-compound-target Network (H-C-T network) was constructed to explore the active compounds and their potential targets. The core compounds were obtained through the H-C-T network. (2) PPI networks were built to analyze the target interactions. Hub targets involved in MGMD treatment of asthma were selected from the PPI network. (3) BP sub-networks were established for classification analysis of BPs in MGMD treatment for asthma. (4) Target pathway network (T-P network) was constructed to show the functional pathways of MGMD for the therapy of asthma. Molecular Docking Molecular docking was conducted to validate if MGMDs compounds could bind to these targets. MS023 The 2D structures of the top five core compounds were downloaded from the TCMSP database (Ru et al., 2014). The structures were added charge and displayed rotatable MS023 keys by AutoDock Tools (version 1.5.6). The protein crystal structures corresponding to the core target genes were downloaded from the Protein Data Bank database (PDB)14 (Burley et al., 2017). Water and hetero molecules of the proteins were removed by Pymol. Hydrogen atoms and charge operations to the proteins was added by AutoDock Tools. The 3D Grid box for molecular docking simulation was also obtained by AutoDock tools was displayed by AutoDock Vina (version 1.1.2) (Trott and Olson, 2010). The results were analyzed and interpreted by PyMOL and Discovery Studio 2020. Results Construction of Herb-Compound-Target Network In this study, 96 active compounds were screened from the six herbs in MGMD. Among them, 51, 19, 7, 6, 8, and 5 compounds were from FF, QH, JG, WM, WWZ, and YCH, respectively. MGMD contains a complex mixture of ingredients, some of them overlapped across 2 herbs, including decursinol, deoxygomisin A, nodakenetin, and naringenin. A total of 92 active compounds were identified after eliminating redundant entries. Five hundred and twenty-three targets were associated with the 92 components identified in MGMD, of which 149 were associated with FF, 151 with QH, 83 with JG, MS023 77 with WM, 23 with WWZ, and 40 with YCH. After eliminating overlapping targets, there were 281 targets remaining. The H-C-T network of MGMD was visualized in Cytoscape (Physique 2). The network contained 379 nodes and 1021 edges. Quercetin showed the highest degree of connectivity in the network with 76 targets, followed by wogonin with 57, luteolin with 55, naringenin with 51, and kaempferol with 40. The properties of the H-C-T network were suitable for displaying complex ingredients, multiple targets, and close interactions between ingredients and targets. Detailed information about the.The seed node of this cluster was ALOX5 (arachidonate 5-lipoxygenase, also known as 5-LO, 5-LOX), an essential enzyme in the metabolism of arachidonic acid, which initiates the biosynthesis of leukotrienes (Bruno et al., 2018). for asthma treatment, including drug-likeness evaluation, oral bioavailability prediction, proteinCprotein conversation (PPI) network construction and analysis, Gene Ontology (GO) terms, and Reactome pathway annotation. Molecular docking was carried out to investigate interactions between active compounds and potential targets. Results A total of 92 active compounds and 72 anti-asthma targets of MGMD were selected for analysis. The GO enrichment analysis results indicated that this anti-asthmatic targets of MGMD mainly participate in inflammatory and in airway remolding processes. The Reactome pathway analysis showed that MGMD prevents asthma mainly through regulation of the IL-4 and IL-13 signaling and the specialized pro-resolving mediators (SPMs) biosynthesis. Molecular docking results suggest that each bioactive compounds (quercetin, wogonin, luteolin, naringenin, and kaempferol) is usually capable to bind with STAT3, PTGS2, JUN, VEGFA, EGFR, and ALOX5. Conclusion This study revealed the active ingredients and potential molecular mechanism by which MGMD treatment is effective against airway inflammation and remodeling in asthma through regulating IL-4 and IL-13 signaling and SPMs biosynthesis. value corrected by the false discovery rate (FDR) algorithm for each term. Network Construction To demonstrate the multi-compound therapeutic features of MGMD, network constructions were performed as follows: (1) herb-compound-target Network (H-C-T network) was constructed to explore the active compounds and their potential targets. The core compounds were obtained through the H-C-T network. (2) PPI networks were built to analyze the target interactions. Hub targets involved in MGMD treatment of asthma were selected from the PPI network. (3) BP sub-networks were established for classification analysis of BPs in MGMD treatment for asthma. (4) Target pathway network (T-P network) was constructed to show the functional pathways of MGMD for the therapy of asthma. Molecular Docking Molecular docking was conducted to validate if MGMDs compounds could bind to these targets. The 2D structures of the top five core compounds were downloaded from the TCMSP database (Ru et al., 2014). The structures were added charge and displayed rotatable keys by AutoDock Tools (version 1.5.6). The protein crystal structures corresponding to the core target genes were downloaded from the Protein Data Bank database (PDB)14 (Burley et al., 2017). Water and hetero molecules of the proteins were removed by Pymol. Hydrogen atoms and charge operations to the proteins was added by AutoDock Tools. The 3D Grid box for molecular docking simulation was also obtained by AutoDock tools was displayed by AutoDock Vina (version 1.1.2) (Trott and Olson, 2010). The results were analyzed and interpreted by PyMOL and Discovery Studio 2020. Results Construction of Herb-Compound-Target Network In this study, 96 active compounds were screened from the six herbs in MGMD. Among them, 51, 19, 7, 6, 8, and 5 substances had been from FF, QH, JG, WM, WWZ, and YCH, respectively. MGMD consists of a complex combination of ingredients, a few of them overlapped across 2 herbal products, including decursinol, deoxygomisin A, nodakenetin, and naringenin. A complete of 92 energetic substances had been identified after removing redundant entries. 500 and twenty-three focuses on had been from the 92 parts determined in MGMD, which 149 had been connected with FF, 151 with QH, 83 with JG, 77 with WM, 23 with WWZ, and 40 with YCH. After removing overlapping focuses on, there have been 281 focuses on staying. The H-C-T network of MGMD was visualized in Cytoscape (Shape 2). The network included 379 nodes and 1021 sides. Quercetin showed the best degree of connection in the network with 76 focuses on, accompanied by wogonin with 57, luteolin with 55, naringenin with 51, and kaempferol with 40. The properties from the H-C-T network had been suitable for showing complex elements, multiple focuses on, and close relationships between elements and focuses on. Detailed information regarding the active substances and focuses on Igf1r determined in MGMD can be demonstrated in Supplementary Desk 1. Open up in another window Shape 2 Herb-Compound-Target network (H-C-T network) of MGMD. Green ellipses represent the herbal products within MGMD; pink gemstones represent active substances in each natural herb; purple gemstones represent active substances distributed by two herbal products, and blue triangles match related focuses on (The IDs from the parts are referred to in Supplementary Desk 1). Potential Asthma Focuses on The focuses on for asthma had been integrated from multi-source directories and your final set of 1,070 disease-related focuses on obtained after removing duplicates (Supplementary Desk 2). 72 overlapping focuses on had been identified as the main element focuses on for learning the anti-asthmatic activity of the MGMD substances.