Unraveling the Antiobesity Potential of Balanites aegyptiaca Leaves through Computational techniques

Exploration of the mechanism of Baitong decoction in the treatment of cold asthma based on network pharmacology and molecular docking


 Background 
 Acute myeloid leukemia (AML) is malignancy of the stem cell precursors of the myeloid lineage occurs due to variations in genetics. Incidence rate of childhood AML in Asian population is 8.4 per million. There is no exact description of AML is Ayurveda, it can be considered into Raktapitta (~bleeding disorder) disease. Hemidesmus indicus (L.) R.Br. (~H. indicus) is described for treatment of Raktapitta. The main treatment for AML is chemotherapy, and patient are searching for Ayurvedic medicines. Hence attempt is made for evaluating activity of H. indicus in AML.
 Objective
 To establish link for therapeutic activity of H. indicus in AML using Network pharmacology and molecular docking study. 
 Materials and methods
 Active compound from root of H. indicus was retrieved from phytochemical based IMPPAT database. ADME (absorption, distribution, metabolism and excretion) study of retrieved active compound done with SwissADME database, and ADME qualified active compound target were obtained with having probability >0.7 from SwissTargetPrediction database. Target of AML retrieved from GeneCard database having relevancy score ≥5.0. To take the common, target of active compound and AML targets from GeneCard are imported into the Venny2.1 database, and the resulting targets used for the analysis. Cytoscape3.9.1 software was used to construct the "drug-active components-target" network diagram from common targets. The PPI (protein-protein interaction) network between proteins was constructed by STRING and result exported to Cytoscape3.9.1 for network analysis to get subnetwork with key target of subnetwork and core targets of overall PPI. GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis of key target from subnetwork done with g-profiler database. Core targets were docked with their corresponding active compound to get docking score.
 Results
 Total of 66 active compound were obtained from H. indicus, On ADME screening 49 active compounds qualified. ADME qualified active compound screened for target and 149 target obtained, after removal of duplicates 81 target were remained. 806 targets of AML were screened from GeneCard database. 19 common targets were obtained between target of active compound and target of AML from GeneCard. These screened 19 targets imported in STRING database to construct PPI network, and obtained result imported into Cytoscape3.9.1 for network analysis, on analysis 1 sub networks with 11 key targets were obtained. Top five H. indicus core targets for AML obtained using “CytoHubba” plug-in. GO and KEGG enrichment analyses were performed on the above-mentioned 11 key targets from sub network, 44 MF (Molecular function), 166 BP (Biological process), 12 CC (Cellular component) and 55 pathways were obtained from the KEGG pathway analyses. Molecular docking results showed that the active component quercetin could spontaneously bind to the core targets EGFR, SRC, AKT1, KDR and IGF1R. EGFR has the best combination with quercetin.
 Conclusion 
 All core targets identified through network analysis of PPI network were linked to common active compound quercetin, and on molecular docking study all core targets showed good docking score to quercetin. Hence, based on this study conclusion can be drawn that the activity of H. indicus is AML might be due to presence of quercetin active compound in it. This study generated link for usefulness of H. indicus is AML.

Simple SummaryCOPD is a lung disease characterized by limited respiratory airflow aggravated with time. JPYF II granules are a traditional Chinese medicine used in the treatment of COPD. However, the main components and potential mechanisms of JPYF II granules are still unclear. The purpose of this study was to elucidate the potential mechanism underlying its ability to treat COPD through network pharmacology, molecular docking, and molecular dynamics simulation techniques. Kaempferol, quercetin, and stigmasterol are the main active compounds in the JPYF II Formula in the treatment of COPD, and AKT1, IL-6, and TNF are potential target proteins for the JPYF II Formula in the treatment of COPD. The potential effective compounds, targets, and related potential molecular mechanisms obtained here provide a reference for follow-up studies on COPD.Background: JianPiYiFei (JPYF) II granules are a Chinese medicine for the treatment of chronic obstructive pulmonary disease (COPD). However, the main components and underlying mechanisms of JPYF II granules are not well understood. This study aimed to elucidate the potential mechanism of JPYF II granules in the treatment of COPD using network pharmacology, molecular docking, and molecular dynamics simulation techniques. Methods: The active compounds and corresponding protein targets of the JPYF II granules were found using the TCMSP, ETCM, and Uniport databases, and a compound–target network was constructed using Cytoscape3.9.1. The COPD targets were searched for in GEO datasets and the OMIM and GeneCards databases. The intersection between the effective compound-related targets and disease-related targets was obtained, PPI networks were constructed, and GO and KEGG enrichment analyses were performed. Then, molecular docking analysis verified the results obtained using network pharmacology. Finally, the protein–compound complexes obtained from the molecular docking analysis were simulated using molecular dynamics (MD) simulations. Results: The network pharmacological results showed that quercetin, kaempferol, and stigmasterol are the main active compounds in JPYF II granules, and AKT1, IL-6, and TNF are key target proteins. The PI3K/AKT signaling pathway is a potential pathway through which the JPYF II granules affect COPD. The results of the molecular docking analysis suggested that quercetin, kaempferol, and stigmasterol have a good binding affinity with AKT1, IL-6, and TNF. The MD simulation results showed that TNF has a good binding affinity with the compounds. Conclusions: This study identified the effective compounds, targets, and related underlying molecular mechanisms of JPYF II granules in the treatment of COPD through network pharmacology, molecular docking, and MD simulation techniques, which provides a reference for subsequent research on the treatment of COPD.

Background Obese type 2 diabetes mellitus (obese T2DM) is one of the prime diseases that endangers human health. Clinical studies have confirmed the ability of the Huanglian Huazhuo capsule to treat obese T2DM; however, its mechanism of action is still unclear. In this study, effects and mechanisms of the Huanglian Huazhuo capsule in obese T2DM were systematically investigated using network pharmacology and molecular docking techniques. Methods The active ingredients and targets of the Huanglian Huazhuo capsule were extracted from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Obese T2DM diabetes-related targets were retrieved from a geographic dataset combined with a gene card database. A protein-protein interaction (PPI) network was constructed to screen core targets. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using Database for Annotation Visualization and Integrated Discovery (DAVID). Interactions between potential targets and active compounds were assessed using molecular docking. Molecular docking was performed on the best core protein complexes obtained using molecular docking. Results A total of 89 and 108 active ingredients and targets, respectively, were identified. Seven core targets were obtained using a topological analysis of the PPI network. The GO and KEGG pathway enrichment analyses showed that the effects of the Huanglian Huazhuo capsules were mediated by inflammation, lipid response, oxidative stress-related genes, and HIF-1 and IL-17 signaling pathways. Good binding ability was observed between the active compounds and screened targets using molecular docking. Conclusions The active ingredients, potential targets, and pathways of the Huanglian Huazhuo capsule for the treatment of obese T2DM were successfully predicted, providing a new strategy for further investigation of its molecular mechanisms. In addition, the potential active ingredients provide a reliable source for drug screening in obese T2DM.

Introduction Obesity is a complex, multifactorial condition characterized by an excessive accumulation of body fat. It is widely recognized as a major public health issue due to its strong association with numerous chronic diseases. [1][2] The use of GLP-1 receptor agonists in obesity treatment began with the recognition that these drugs, initially developed for type 2 diabetes, could significantly reduce body weight due to their effects on appetite regulation and satiety. Liraglutide was the first to be approved specifically for obesity, followed by semaglutide, The development of tirzepatide, which targets both GLP-1 and GIP receptors, has further expanded the potential for obesity treatment. As clinical evidence continues to support their efficacy and safety, GLP-1 receptor agonists are becoming an important tool in the management of obesity, offering a promising option for individuals struggling with weight and related health conditions [3][4][5]. Aim of the study The aim of this study was to compare the effectiveness of semaglutide, liraglutide and tirzepatide in reducing body weight in obesity. Materials and methods The article was created based on the PubMed and Cochrane databases. The literature was analyzed using the fallow keywords: Obesity treatment, liraglutide, tirzepatide, semaglutide, glucagon-like peptide-1 (GLP-1) receptor agonists Results The research proved that tirzepatide is more effective in reducing body weight compared to semaglutide and liraglutide [6][7]. Conclusion Thanks to the comparison of results from multiple studies, we can assume that, at this point, tirzepatide is the most effective pharmacological treatment for obesity, which, when used in combination with lifestyle changes, provides a lasting effect on weight reduction and, consequently, helps treat obesity-related comorbidities[6][8].

This study aims to investigate the therapeutic mechanism of Liangxue Jiedu oral liquid in treating psoriasis vulgaris using the network pharmacology and molecular docking. Active compounds and their corresponding targets of Liangxue Jiedu oral liquid were obtained using the TCMSP database, and protein and gene names were standardized using the Uniprot database. A medicinal material-active compound–target interaction network was structured utilizing Cytoscape software. The targets associated with psoriasis vulgaris were collected from the GeneCards database, and a protein–protein interaction network of common targets of the disease and active compounds was established using the STRING database with core targets screened via Cytoscape software package. Gene Ontology and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses were conducted using the DAVID database. Furthermore, molecular docking was performed using PyMoL and AutoDock Vina to predict the binding affinities between core targets and active compounds. A total of 174 active ingredients and 27 key targets in Liangxue Jiedu oral liquid were identified, with core targets including tumor necrosis factor, albumin, interleukin 6, tumor protein 53, and interleukin 1 beta. These targets were closely associated with diseases such as atherosclerosis, cancer, diabetes, hepatitis B, and cellular immunity, as indicated by Kyoto Encyclopedia of Gene and Genome pathway enrichment analysis. Molecular docking results demonstrated strong binding affinities between the main active ingredients and the target proteins. This study integrates network pharmacology and molecular docking techniques to reveal the potential mechanisms of the oral liquid Liangxue Jiedu in treating plaque psoriasis, laying a foundation for further pharmacological research.

To explore the potential active compounds and molecular mechanism of Xuefu Zhuyu decoction (XFZYD) in the treatment of atherosclerosis (AS) based on network pharmacology and molecular docking.The effective components and action targets of XFZYD were screened by using TCMSP database. And then, the action targets of AS were collected by GeneCards database. The intersection targets between the effective components’ targets of XFZYD and AS-related action targets were used to construct PPI networks. GO and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed on these intersection targets. Finally, molecular docking software was used to excavate the active compounds of the core targets VEGFA and AKT1.We detected 225 active components of XFZYD, and found that quercetin, kaempferol, luteolin, naringenin, β-sitosterol, isorhamnetin, stigmasterol, baicalein, nobiletin, and β-carotene are the potential active compounds of XFZYD; STAT3, IL6, JUN, VEGFA, MAPK14, and AKT1 are the core target proteins of the active compounds, among which VEGFA and AKT1 are the key target proteins. PPI network results showed that β-carotene, quercetin, kaempferol, luteolin, and naringenin had higher degree values and more corresponding targets than other 5 active compounds and had the stable binding ability to regulatory proteins VEGFA and AKT1. The core components β-carotene, quercetin, kaempferol, and luteolin exerted their therapeutic effects on AS by acting on the key target proteins VEGFA and AKT1 to regulate fluid shear stress and the AGE-RAGE signaling pathway and IL-17 signaling pathway of diabetic complications of AS. The molecular docking results showed that VEGFA and AKT1 had great docking ability with the targeted active compounds, and β-carotene is the best.The active components of XFZYD, including β -carotene, quercetin, kamanol, and luteolin, can act on VEGFA and AKT1. These active ingredients play a role in alleviating and treating AS by regulating fluid shear stress and participating in signaling pathways such AS AGE-RAGE of atherosclerosis and diabetes mellitus complicated with AS. β-carotene is a potential inhibitor of VEGFA and AKT1 and treats AS through antioxidant action.

Background:Ginkgo biloba L. leaves (GBLs) play a substantial role in the treatment of vascular dementia (VD); however, the underlying mechanisms of action are unclear.Objective:This study was conducted to investigate the mechanisms of action of GBLs in the treatment of VD through network pharmacology, molecular docking, and molecular dynamics simulations.Methods:The active ingredients and related targets of GBLs were screened using the traditional Chinese medicine systems pharmacology, Swiss Target Prediction and GeneCards databases, and the VD-related targets were screened using the OMIM, DrugBank, GeneCards, and DisGeNET databases, and the potential targets were identified using a Venn diagram. We used Cytoscape 3.8.0 software and the STRING platform to construct traditional Chinese medicine–active ingredient–potential target and protein–protein interaction networks, respectively. After gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of potential targets using the DAVID platform, the binding affinity between key active ingredients and targets was analyzed by molecular docking, and finally, the top 3 proteins–ligand pairs with the best binding were simulated by molecular dynamics to verify the molecular docking results.Results:A total of 27 active ingredients of GBLs were screened and 274 potential targets involved in the treatment of VD were identified. Quercetin, luteolin, kaempferol, and ginkgolide B were the core ingredients for treatment, and AKT1, TNF, IL6, VEGFA, IL1B, TP53, CASP3, SRC, EGFR, JUN, and EGFR were the main targets of action. The main biological processes involved apoptosis, inflammatory response, cell migration, lipopolysaccharide response, hypoxia response, and aging. PI3K/Akt appeared to be a key signaling pathway for GBLs in the treatment of VD. Molecular docking displayed strong binding affinity between the active ingredients and the targets. Molecular dynamics simulation results further verified the stability of their interactions.Conclusion subsections:This study revealed the potential molecular mechanisms involved in the treatment of VD by GBLs using multi-ingredient, multi-target, and multi-pathway interactions, providing a theoretical basis for the clinical treatment and lead drug development of VD.

Objective To explore the potential molecular mechanism of Pueraria Lobata Radix (RP) and Salviae Miltiorrhizae Radix (RS) in the treatment of type 2 diabetes mellitus (T2DM) based on network pharmacology and molecular docking. Methods The chemical constituents and core targets of RP and RS were searched by Traditional Chinese Medicine System Pharmacology (TCMSP); target genes related to T2DM were obtained through GeneCards database, component target network diagram was constructed, intersection genes of active compounds and T2DM were synthesized, protein-protein interaction (PPI) relationship was obtained, and core targets were screened by using Cytoscape 3.7.2. Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were analyzed utilizing R studio 4.0.4 according to David database. Based on molecular docking, the screened active components of RP and RS were verified by molecular docking with the core target using Discovery Studio 2019. Results There were totally 92 components and 29 corresponding targets in the component target network of RP and RS drug pair, of which 6 were the core targets of RP and RS in the treatment of T2DM. Molecular docking results showed that the active compounds of puerarin, formononetin, tanshinone iia, and luteolin had better binding activity with AKT1, VEGFA, NOS3, PPARG, MMP9, and VCAM1, respectively. Among them, puerarin showed significant effects in activating NOS3 pathway and luteolin exhibited significant effects in activating MMP9 pathway, respectively. The main biological processes mainly including xenobiotic stimulus, response to peptide, gland development, response to radiation, cellular response to chemical stress, response to oxygen levels, and the main signal pathways include response to xenobiotic stimulus, cellular response to chemical stress, response to peptide, gland development, and response to oxygen levels. Conclusion Network pharmacology is an effective tool to explain the action mechanism of Traditional Chinese Medicine (TCM) from the overall perspective. RP and RS pair could alleviate T2DM via the molecular mechanism predicted by the network pharmacology, which provided new ideas and further research on the molecular mechanism of T2DM.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which primarily affects the joints. The aim of the present study was to predict the main active ingredients of Jiawei Guizhishaoyaozhimu Decoction (JWGZSYZMD) and potential targets of this treatment during RA therapy by using molecular docking and network pharmacology methods. In addition, another aim was to investigate the therapeutic effects and mechanism of JWGZSYZMD on joint inflammation in rat models of collagen Ⅱ-induced arthritis (CIA). JWGZSYZMD ingredients and targets and genes associated with RA first extracted from traditional Chinese medicine (TCM) Systems Pharmacology Database and Analysis Platform, Bioinformatics Analysis Tool of Molecular Mechanism-TCM and Genecards databases, which were then transferred to the STRING database to set up protein interaction networks. The crystal structures of target proteins were also downloaded from the Protein Data Bank before molecular docking of compounds onto the protein targets was performed using AutoDock Vina software. In addition, a drug compound target visualization network was constructed using Cytoscape 3.7.2 software, which was used to elucidate the main mechanism underlying the anti-RA effect of JWGZSYZMD. A CIA rat model was established and animals were divided into the control, CIA model, JWGZSYZMD treatment (low-, medium- and high-dose) and tripterygium glycoside groups. Compared with the rats in the CIA model group, the joint scores of the rats in the high-dose group of JWGZSYZMD were significantly lower after 21 days of treatment. The expression levels of IL-6, TNF-α, IL-1β and IL-17A in the synovial supernatant of the model rats were lower compared with those in the CIA group. Also, the expression of the aforementioned cytokines in the high-dose JWGZSYZMD group was significantly lower compared with those in the CIA model group. To conclude, using molecular docking combined with network pharmacology, the material basis and molecular mechanism underlying the effects of JWGZSYZMD during RA therapy were studied, which could potentially provide a reference for future clinical applications.

Tripterygium wilfordii Hook F (TwHF) is a prominent Chinese herbal formula. It exhibits significant clinical efficacy in treating systemic lupus erythematosus (SLE), though its mechanisms remain unclear. Our study employs network pharmacology and molecular docking to explore active compounds of TwHF and their associated targets for SLE treatment. Primary active compounds of TwHF and their targets were sourced from the TCMSP, SwissTargetPrediction, and UniProt databases. SLE-relevant target proteins were identified from the OMIM and GeneCards databases. Enrichment analyses were conducted to reveal results of common TwHF-SLE targets. STRING and Cytoscape software were used to systematically analyze and construct protein-protein interaction (PPI) networks, compound-target-pathway, and target-organ networks. Molecular docking was utilized to confirm the binding of key targets to the top active compounds. A total of 14 active compounds and 300 overlapping targets between TwHF and SLE were identified. PPI network analysis revealed 29 core targets. Several pathways were found to contribute to the potential therapeutic effects of TwHF in SLE, including PI3K-Akt signaling pathway, Th17 cell differentiation, chemokine signaling, and T cell receptor signaling. Disease Ontology (DO) analysis highlighted the involvement of TwHF in genes associated with myocardial infarction (MI), atherosclerosis (AS), breast carcinoma, and ischemia. Molecular docking results demonstrated strong binding affinities, with 37 signal molecule-receptor interactions in SLE and 97 interactions in SLE-related MI and AS showing binding energies lower than -7kJ/mol. This research effectively anticipates the potent constituents, probable targets, and pathways implicated in treating SLE with TwHF, specifically addressing complications such as MI and AS. Comprehending the precise molecular mechanism targeting SLE of TwHF and its efficacious bioactive components furnishes a theoretical groundwork for enhancing its clinical utilization. Key Points •SLE is characterized by aberrant immune activation and persistent inflammation. •TwHF exerts immunomodulatory and anti-inflammatory effects. •TwHF exhibits prospects in the treatment of SLE with unknown molecular mechanisms. •Network pharmacology and molecular docking reveal promise in the mechanism of TwHF.

This research aims to explore how Puerariae Lobatae Radix regulates sebaceous gland secretion using network pharmacology, and validate its effects on important targets through animal studies. This study utilized UPLC-EQ-MS to analyze Puerariae Lobatae Radix extract and identify potential bioactive compounds. Predicted targets of these compounds were obtained from the Swiss Target Prediction database, while targets associated with sebaceous gland secretion were obtained from the GeneCards database. Common targets between the databases were identified and a protein-protein interaction (PPI) network was established using the STRING platform. The PPI network was further analyzed using Cytoscape software. Pathway enrichment analysis was performed using Reactome, and molecular docking experiments targeted pivotal pathway proteins. Animal experiments were then conducted to validate the regulatory effects of the primary active compounds of Puerariae Lobatae Radix on key pathway proteins. This research identified 17 active compounds in Puerariae Lobatae Radix and 163 potential targets associated with the regulation of sebum secretion. Pathway enrichment analysis indicates that these targets may modulate lipid metabolism pathways through involvement in peroxisome proliferator-activated receptor α, SREB, steroid metabolism, and arachidonic acid metabolism pathways. Molecular docking analysis demonstrates that puerarin and daidzein show favorable binding interactions with key targets in these pathways. Animal experiments demonstrated that the administration of Puerariae Lobatae Radix resulted in a significant reduction in the area of sebaceous gland patches compared to the control group. Histological analysis revealed notable alterations in the structure of sebaceous glands, including reductions in size, thickness, and density. Furthermore, the expression levels of TG, DHT, and IL-6 were significantly decreased in the Puerariae Lobatae Radix group (p < 0.05), and immunoblotting indicated a significant decrease in the expression of PPARG and ACC1 (p < 0.05). This study demonstrates that Puerariae Lobatae Radix can regulate skin lipid metabolism by targeting multiple pathways. The primary mechanism involves inhibiting sebaceous gland growth and reducing TG secretion by modulating the expression of PPARG and ACC1. Puerarin and Daidzein are identified as key bioactive compounds responsible for this regulatory effect. These findings highlight the therapeutic potential of Puerariae Lobatae Radix in addressing sebaceous gland-related conditions.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease, the incidence of which increases annually. Shugan Xiaozhi (SGXZ) decoction, a composite traditional Chinese medicinal prescription, has been demonstrated to exert a therapeutic effect on NAFLD. In this study, the potential bioactive ingredients and mechanism of SGXZ decoction against NAFLD were explored via network pharmacology, molecular docking, and molecular dynamics simulation. Compounds in SGXZ decoction were identified and collected from the literature, and the corresponding targets were predicted through the Similarity Ensemble Approach database. Potential targets related to NAFLD were searched on DisGeNET and GeneCards databases. The compound-target-disease and protein-protein interaction (PPI) networks were constructed to recognize key compounds and targets. Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed on the targets. Molecular docking was used to further screen the potent active compounds in SGXZ. Finally, molecular dynamics (MD) simulation was applied to verify and validate the binding between the most potent compound and targets. A total of 31 active compounds and 220 corresponding targets in SGXZ decoction were collected. Moreover, 1,544 targets of NAFLD were obtained, of which 78 targets intersected with the targets of SGXZ decoction. Key compounds and targets were recognized through the compound-target-disease and PPI network. Multiple biological pathways were annotated, including PI3K-Akt, MAPK, insulin resistance, HIF-1, and tryptophan metabolism. Molecular docking showed that gallic acid, chlorogenic acid and isochlorogenic acid A could combine with the key targets. Molecular dynamics simulations suggested that isochlorogenic acid A might potentially bind directly with RELA, IL-6, VEGFA, and MMP9 in the regulation of PI3K-Akt signaling pathway. This study investigated the active substances and key targets of SGXZ decoction in the regulation of multiple-pathways based on network pharmacology and computational approaches, providing a theoretical basis for further pharmacological research into the potential mechanism of SGXZ in NAFLD.

Objective: The objective was to study the potential substance basis and action mechanism of Chuanxiong Rhizoma (CX) and Angelicae Dahuricae Radix (AD) on analgesia through network pharmacology and molecular docking. Materials and Methods: The active components and targets of CX and AD and pain-related genes were retrieved through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and GeneCards database. Then, the co-action targets were found, protein–protein interaction network was constructed by the String database. The Cytoscape 3.7.1 was used to construct “CX-AD-active components-pain” network. Further enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out to predict its mechanism of action, the top four active components in the network were docked with the targets. Results: There are 26 compounds, 45 targets in the network. Among them, (Z)-ligustilide and beta-sitosterol, respectively, have more potential targets in CX and AD, and prostaglandin-endoperoxide synthase (PTGS2), PTGS1 have more ligands. GO analysis shows that molecular functions of CX and AD mainly performed through the G protein-coupled amine receptor activity, adrenergic receptor activity, and catecholamine binding. KEGG analysis indicates that they could exert analgesic effect on the pathways of regulating neuroactive ligand-receptor interaction, serotonergic synapse, and cGMP-PKG signaling pathway. Molecular docking results show that the active compounds are highly compatible with the structure of the protein receptor, and they interact through the hydrogen bond and π–π bond between the ligand and the active site residues. Conclusions: Through network pharmacology and molecular docking, this study preliminarily revealed the main active components, targets, and potential regulation network of CX and AD, providing a reference for the subsequent experimental research.

Eucommia ulmoides (EU) and its diverse extracts have demonstrated antioxidative, anti-inflammatory, and cytoprotective properties against hepatic ischemia–reperfusion injury (HIRI). However, the primary constituents of EU and their putative mechanisms remain elusive. This study aims to explore the potential mechanisms of EU in the prevention and treatment of HIRI by employing network pharmacology and molecular docking methodologies. The main components and corresponding protein targets of EU were searched in the literature and TCMSP, and the compound target network was constructed by Cytoscape 3.9.1. Liver ischemia–reperfusion injury targets were searched in OMIM and GeneCards databases. The intersection points of compound targets and disease targets were obtained, and the overlapping targets were imported into the STRING database to construct the PPI network. We further analyzed the targets for GO and KEGG enrichment. Finally, molecular docking studies were performed on the core targets and active compounds. The component-target network unveiled a total of 26 efficacious bioactive compounds corresponding to 207 target proteins. Notably, the top-ranking compounds based on degree centrality were quercetin, β-sitosterol, and gallic acid. Within the PPI network, the highest degree centrality encompassed RELA, AKT1, TP53. GO and KEGG enrichment analysis elucidated that EU in HIRI primarily engaged in positive regulation of gene expression, positive transcriptional regulation via RNA polymerase II promoter, negative modulation of apoptotic processes, positive regulation of transcription from DNA templates, and drug responsiveness, among other biological processes. Key pathways included cancer pathways, RAGE signaling pathway, lipid metabolism, atherosclerosis, TNF signaling pathway, PI3K-Akt signaling pathway, and apoptotic pathways. Molecular docking analysis revealed robust affinities between quercetin, β-sitosterol, gallic acid, and RELA, AKT1, TP53, respectively. This study reveals EU exhibits substantial potential in mitigating and treating HIRI through multifaceted targeting and involvement in intricate signaling pathways.