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The study aims to investigate the effects of curcumin on radiation/chemotherapy-induced oral mucositis (R/CIOM) and preliminarily explore its mechanism. Randomized controlled trials were identified from the PubMed, Embase, Web of Science, Cochrane Library, Medline, and Google Scholar databases. RevMan 5.4 was used for statistical analysis to calculate the combined risk ratios (RRs). The mechanism was analyzed through network pharmacology, molecular docking, and a molecular dynamics simulation. The targets of curcumin were collected in HERB, PharmMapper, Targetnet, Swiss Target Prediction, and SuperPred. OMIM, GeneCards, and Disgenet were used to collect relevant targets for R/CIOM. Cytoscape software 3.8.0 was used to construct the component-target-pathway network. Protein–Protein Interaction (PPI) networks were constructed using the STRING database. GO and KEGG enrichment analyses were performed by Metascape. AutoDock Vina 4.2 software was used for molecular docking. The molecular dynamics simulation was performed by Gromacs v2022.03. It is found that 12 studies involving 565 patients were included. Meta-analyses showed that curcumin reduced the incidence of severe R/CIOM (RR 0.42 [0.24, 0.75]) and the mean severity of R/CIOM (MD -0.93 [−1.34, −0.52]). Eleven core target genes were identified in the treatment of R/CIOM with curcumin. The results of molecular docking and the molecular dynamics simulation showed that curcumin had strong binding energy and stability with target proteins including MAPK3, SRC, and TNF. Overall, these findings suggest curcumin can effectively improve severe R/CIOM, perhaps by affecting MAPK3, SRC, and TNF.

Gynostemma pentaphyllum (Thunb.) Makino (GP), a plant with homology of medicine and food, as a traditional Chinese medicine, possesses promising biological activities in the prevention and treatment of type 2 diabetes mellitus (T2DM). However, the material basis and the mechanism of action of GP in the treatment of T2DM have not been fully elucidated. This study aimed to clarify the active components, potential targets and signaling pathways of GP in treating T2DM. The chemical ingredients of GP were collected by combining UPLC-HRMS analysis and literature research. Network pharmacology revealed that GP had 32 components and 326 potential targets in treating T2DM. The results showed that GP affected T2DM by mediating the insulin resistance signaling pathway, PI3K/Akt signaling pathway and FoxO1 signaling pathway, which had a close relationship with T2DM. Molecular docking results showed that STAT3, PIK3CA, AKT1, EGFR, VEGFA and INSR had high affinity with the active compounds of GP. In vitro, GP extracts obviously increased the glucose uptake and glucose consumption in IR-HepG2 cells. GP extracts increased the levels of PI3K, p-AKT, p-GSK3β and p-FoxO1 and decreased the expression of p-IRS1, p-GS, PEPCK and G6Pase, which indicated that GP could promote glycogen synthesis and inhibit gluconeogenesis by regulating the IRS1/PI3K/Akt signaling pathway. The results demonstrated that GP could improve insulin resistance by promoting glucose uptake and glycogen synthesis and inhibiting gluconeogenesis through regulating the IRS1/PI3K/Akt signaling pathway, which might be a potential alternative therapy for T2DM.

Hyperlipidemia is a prevalent chronic metabolic disease that severely affects human health. Currently, commonly used clinical therapeutic drugs are prone to drug dependence and toxic side effects. Dietary intervention for treating chronic metabolic diseases has received widespread attention. Rosa sterilis is a characteristic fruit tree in China whose fruits are rich in flavonoids, which have been shown to have a therapeutic effect on hyperlipidemia; however, their exact molecular mechanism of action remains unclear. Therefore, this study aimed to investigate the therapeutic effects of R. sterilis total flavonoid extract (RS) on hyperlipidemia and its possible mechanisms. A hyperlipidemic zebrafish model was established using egg yolk powder and then treated with RS to observe changes in the integral optical density in the tail vessels. Network pharmacology and molecular docking were used to investigate the potential mechanism of action of RS for the treatment of hyperlipidemia. The results showed that RS exhibited favorable hypolipidemic effects on zebrafish in the concentration range of 3.0–30.0 μg/mL in a dose-dependent manner. Topological and molecular docking analyses identified HSP90AA1, PPARA, and MMP9 as key targets for hypolipidemic effects, which were exerted mainly through lipolytic regulation of adipocytes and lipids; pathway analysis revealed enrichment in atherosclerosis, chemical carcinogenic-receptor activation pathways in cancers, and proteoglycans in prostate cancer and other cancers. Mover, chinensinaphthol possessed higher content and better target binding ability, which suggested that chinensinaphthol might be an important component of RS with hypolipidemic active function. These findings provide a direction for further research on RS interventions for the treatment of hyperlipidemia.

The high recurrence rate of cervical cancer is a leading cause of cancer deaths in women. 5-Fluorouracil (5-FU) is an antitumor drug used to treat many types of cancer, but its diminishing effectiveness and side effects limit its use. Norcantharidin (NCTD), a demethylated derivative of cantharidin, exhibits various biological activities. Here, we investigated whether NCTD could potentiate 5-FU to induce cervical cancer cell death. To assess the cell viability and synergistic effects of the drugs, cell counting kit-8 and colony formation assays were performed using HR-HPV-positive cervical cancer cell lines. Annexin V-FITC/PI staining and TUNEL assays were performed to confirm the induction of apoptosis. The synergistic effect of NCTD on the antitumor activity of 5-FU was analyzed using network pharmacology, molecular docking, and molecular dynamics simulations. Apoptosis-related proteins were examined using immunoblotting. The combination of NCTD and 5-FU was synergistic in cervical cancer cell lines. Network pharmacological analysis identified 10 common targets of NCTD and 5-FU for cervical cancer treatment. Molecular docking showed the strong binding affinity of both compounds with CA12, CASP9, and PTGS1. Molecular dynamics simulations showed that the complex system of both drugs with caspase-9 could be in a stable state. NCTD enhanced 5-FU-mediated cytotoxicity by activating apoptosis-related proteins. NCTD acts synergistically with 5-FU to inhibit cervical cancer cell proliferation. NCTD enhances 5-FU-induced apoptosis in cervical cancer cell lines via the caspase-dependent pathway.

Background: Pulmonary arterial hypertension (PAH) is a serious disease characterized by increased pressure in the pulmonary arteries, which can lead to heart failure and death. Chlorogenic acid (CGA) is a natural compound present in several foods and medicinal plants and has been described to exert a therapeutic effect in various diseases. However, its potential therapeutic effect on PAH remains undeciphered. In this study, the potential of CGA for the treatment of PAH was investigated using network pharmacology analysis and molecular docking. Methods: Potential CGA targets were obtained from the SwissTargetPrediction and GeneCards databases. Moreover, potential PAH targets were collected from the GeneCards and DisGNET databases. Then, common targets were selected, and a protein-protein network (PPI) was constructed between common CGA and PAH targets using the STRING database. The common hub targets were selected, and GO enrichment analysis was performed via KEGG using the DAVID 6.8 database. Additionally, molecular docking analysis was performed to investigate the interaction between CGA and these potential therapeutic targets. Results: We obtained 168 potential targets for CGA and 5779 potential targets associated with PAH. Among them, 133 were common to both CGA and PAH. The main hub targets identified through PPI network analysis were TP53, HIF1A, CASP3, IL1B, JUN, MMP9, CCL2, VEGFA, SRC, IKBKB, MMP2, CASP8, NOS3, MMP1, and CASP1. KEGG pathway analysis showed that these hub targets are associated with pathways such as lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the IL-17 signaling pathway. In addition, the molecular docking results showed a high binding affinity between CGA and the 15 hub PAH-associated targets, further supporting its therapeutic potential. Conclusions: This study provides preliminary evidence on the underlying molecular mechanism of CGA in the treatment of PAH. The findings suggest that CGA could be a promising option for the development of new PAH drugs.

This study aimed to explore the liver protective effects of a fourth-generation glycyrrhizic acid product (magnesium isoglycyrrhizinate injection, MII) in the treatment of mice with drug-induced liver injury—specifically, to determine its effects on plasma metabolites. Moreover, the possible mechanism of its intervention in lipid metabolism and amino acid metabolism through the liver protective effect was preliminarily explored, combined with network pharmacology. The liver injury model of mice was established using acetaminophen (APAP). The protective effect of MII on the mice model was evaluated using pathological tissue sections and biochemical indices such as alanine transaminase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD). Metabolomics analysis of plasma was performed using the UHPLC-QTOF/MS technique to screen for potential biomarkers and enriched metabolic pathways. The potential targets and pathways of MII were predicted by network pharmacology, and the mechanism was verified by Western blot analysis. MII significantly improved the pathological liver changes in mice with liver injury. The content of ALT and AST was decreased, and the activity of SOD was increased significantly (p < 0.05, 0.01). A total of 29 potential biomarkers were identified in the metabolomics analysis, mainly involving seven pathways, such as lipid metabolism and amino acid metabolism. A total of 44 intersection targets of MII in the treatment of liver injury were obtained by network pharmacology, involving lipid metabolism and other related pathways. Western blot analysis results showed that MII could significantly reduce the expression of JAK2 and STAT3. MII can effectively ameliorate liver injury in modeled mice through related pathways such as lipid metabolism and amino acid metabolism. This study could provide not only a scientific basis for the elucidation of the mechanism of action of MII in exerting a hepatoprotective effect, but also a reference for its rational clinical application.

Background: Glaucoma is a progressive optic neuropathy characterized by the neurodegeneration and death of retinal ganglion cells (RGCs), leading to blindness. Current glaucoma interventions reduce intraocular pressure but do not address retinal neurodegeneration. In this effort, to identify new pharmacological targets for glaucoma management, we employed a network pharmacology approach. Methods: We first retrieved transcriptomic data from GEO, an NCBI database, and carried out GEO2R (an interactive web tool aimed at comparing two or more groups of samples in a GEO dataset). The GEO2R statistical analysis aimed at identifying the top differentially expressed genes (DEGs) and used these as input of STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) app within Cytoscape software, which builds networks of proteins starting from input DEGs. Analyses of centrality metrics using Cytoscape were carried out to identify nodes (genes or proteins) involved in network stability. We also employed the web-server software MIRNET 2.0 to build miRNA–target interaction networks for a re-analysis of the GSE105269 dataset, which reports analyses of microRNA expressions. Results: The pharmacological targets, identified in silico through analyses of the centrality metrics carried out with Cytoscape, were rescored based on correlations with entries in the PubMed and clinicaltrials.gov databases. When there was no match (82 out of 135 identified central nodes, in 8 analyzed networks), targets were considered “potential innovative” targets for the treatment of glaucoma, after further validation studies. Conclusions: Several druggable targets, such as GPCRs (e.g., 5-hydroxytryptamine 5A (5-HT5A) and adenosine A2B receptors) and enzymes (e.g., lactate dehydrogenase A or monoamine oxidase B), were found to be rescored as “potential innovative” pharmacological targets for glaucoma treatment.

Background: Obesity is gradually becoming a widespread health problem, and treatment using natural compounds has seen an increasing trend. As a by-product of hazelnut, hazel leaf is usually disposed of as waste, but it is widely used in traditional and folk medicines around the world. Aim of this study: Based on previous studies, the effects of the regulation of lipid metabolism and the mechanism of hazel leaf polyphenol extraction obesity were investigated. Methods: In this study, a high-fat diet-fed mouse model of obesity and 3T3-L1 preadipocytes were established. The ameliorative effects of the hazel leaf polyphenol extract on obesity and the regulating lipid metabolisms were explored based on network pharmacology, gut microbiota, and molecular docking. Results: Network pharmacology showed that hazel leaf polyphenols may play a role by targeting key targets, including PPARγ, and regulating the PPAR signaling pathway. They significantly improved body weight gain, the liver index, and adiposity and lipid levels; regulated the gut microbiota and short-chain fatty acid contents; down-regulated the expression of lipid synthesis proteins SREBP1c, PPARγ, and C/EBP-α; and up-regulated the expression of p-AMPK in obese mice. They inhibited the differentiation of 3T3-L1 cells, and the expression of related proteins is consistent with the results in vivo. The molecular docking results indicated that gallic acid, quercetin-3-O-beta-D-glucopyranoside, quercetin, myricetin, and luteolin-7-O-glucoside in the hazel leaf polyphenol extract had strong binding activities with PPARγ, C/EBP-α, and AMPK. Conclusions: The results demonstrate that the hazel leaf polyphenol extract can improve obesity by regulating lipid metabolism, which provides a valuable basis for developing health products made from hazel leaf polyphenols in the future.

A combination of network pharmacology, molecular docking and ADME/drug-likeness predictions was employed to explore the potential of Salvia officinalis compounds to interact with key targets involved in the pathogenesis of T2DM. These were predicted using the SwissTargetPrediction, Similarity Ensemble Approach and BindingDB databases. Networks were constructed using the STRING online tool and Cytoscape (v.3.9.1) software. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis and molecular docking were performed using DAVID, SHINEGO 0.77 and MOE suite, respectively. ADME/drug-likeness parameters were computed using SwissADME and Molsoft L.L.C. The top-ranking targets were CTNNB1, JUN, ESR1, RELA, NR3C1, CREB1, PPARG, PTGS2, CYP3A4, MMP9, UGT2B7, CYP2C19, SLCO1B1, AR, CYP19A1, PARP1, CYP1A2, CYP1B1, HSD17B1, and GSK3B. Apigenin, caffeic acid, oleanolic acid, rosmarinic acid, hispidulin, and salvianolic acid B showed the highest degree of connections in the compound-target network. Gene enrichment analysis identified pathways involved in insulin resistance, adherens junctions, metabolic processes, IL-17, TNF-α, cAMP, relaxin, and AGE-RAGE in diabetic complications. Rosmarinic acid, caffeic acid, and salvianolic acid B showed the most promising interactions with PTGS2, DPP4, AMY1A, PTB1B, PPARG, GSK3B and RELA. Overall, this study enhances understanding of the antidiabetic activity of S. officinalis and provides further insights for future drug discovery purposes.

This study investigated the batch stability of egg white peptides (EWPs) during the enzymatic hydrolysis process, and confirmed the potential application of four crucial four peptides inoxidative damage repair. The results revealed that different batches of EWPs had good stability relating to antioxidant activity. With a similar sequence to confirmed antioxidant peptides, four EWPs (QMDDFE, WDDDPTD, DEPDPL, and FKDEDTQ) were identified withhigh repetition rates, and their potential to repair oxidative damage was investigated. Network pharmacology results showed that these four peptides could regulate the targets related to oxidative damage. Enrichment results demonstrated that these four peptides could influence the targets and pathways related to glutathione transferase activity (enrichment score: 148.0) and glutathione metabolism (p value: 9.22 × 10−10). This study could provide evidence for the batch stability of hydrolyzed prepared EWPs, and offer theoretical support for the development of antioxidant damage ingredients derived from foods.

Obesity, characterized by the excessive accumulation of fat, is a prevalent metabolic disorder that poses a significant global health concern. Triphala, an herbal combination consisting of Phyllanthus emblica Linn, Terminalia chebula Retz, and Terminalia bellerica (Gaertn) Roxb, has emerged as a potential solution for addressing concerns related to obesity. This study aimed to investigate the network pharmacology and molecular docking of Triphala to identify its bioactive ingredients and their interactions with pathways associated with obesity. The bioactive compounds present in Triphala and genes linked to obesity were identified, followed by an analysis of the protein-protein interaction networks. Enrichment analysis, including Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, was conducted. Prominent genes and compounds were selected for further investigation through molecular docking studies. The study revealed a close correlation between obesity and the AKT1 and PPARG genes. The observed binding energy between beta-sitosterol, 7-dehydrosigmasterol, peraksine, α-amyrin, luteolin, quercetin, kaempferol, ellagic acid, and phyllanthin with AKT1 and PPARG indicated a favorable binding affinity. In conclusion, nine compounds showed promise in regulating these genes for obesity prevention and management. Further research is required to validate their specific effects.

Alzheimer’s disease (AD) is an age-associated neurodegenerative condition marked by amyloid plaques, synaptic dysfunction, and neuronal loss. Besides conventional medical care, herbal therapies, both raw and refined, have attracted researchers for their potential therapeutic effects. As a proof-of-concept, our study combined HPLC-DAD analysis of bioactive constituents, network pharmacology, molecular dynamics (MD), molecular docking, post-MD analysis, and experimental verification to investigate the mechanisms of crude drug formulations as a therapeutic strategy for AD. We identified nine bioactive compounds targeting 188 proteins and 1171 AD-associated genes. Using a Venn diagram, we found 47 overlapping targets, forming “herb-compound-target (HCT)” interaction networks and a protein‒protein interaction (PPI) network. Simulations analyzed binding interactions among the three core targets and their compounds. MD assessed the stability of the best-ranked poses and beneficial compounds for each protein. Among the top 22 hub genes, AChE, BChE, and MAO, ranked 10, 14, and 34, respectively, were selected for further analysis. Two tetraherbal formulations, Form A and Form B, showed notable activity against AChE. Form A exhibited significant (p < 0.0001) inhibitory activity (IC50 = 114.842 ± 2.084 µg/mL) compared to Form B (IC50 = 142.829 ± 4.258 µg/mL), though weaker than galantamine (IC50 = 27.950 ± 0.122 µg/mL). Form B had significant inhibitory effects on BChE (IC50 = 655.860 ± 32.812 µg/mL) compared to Form A (IC50 = 679.718 ± 20.656 µg/mL), but lower than galantamine (IC50 = 23.126 ± 0.683 µg/mL). Both forms protected against Fe2+-mediated brain injury by inhibiting MAO. Docking identified quercetin (−10.2 kcal/mol) and myricetin (−10.1 kcal/mol) for AChE; rutin (−10.6 kcal/mol) and quercetin (−9.7 kcal/mol) for BChE; and kaempferol (−9.1 kcal/mol) and quercetin (−8.9 kcal/mol) for MAO. These compounds were thermodynamically stable based on MD analysis. Collectively, the results offer a scientific rationale for the use of these specifically selected medicinal herbs as AD medications.

Objectives: Network pharmacology is essential for understanding the multi-target and multi-pathway therapeutic mechanisms of traditional Chinese medicine. This study aims to evaluate the influence of database quality on target identification and to explore the therapeutic potential of rhynchophylline (Rhy) in treating overactive bladder (OAB). Methods: An OAB dataset was constructed through extensive literature screening. Using this dataset, we applied network pharmacology to predict potential targets for Rhy, which is known for its therapeutic effects but lacks a well-defined target profile. Predicted targets were validated through in vitro experiments, including DARTS and CETSA. Results: Our analysis identified Rhy as a potential modulator of the M3 receptor and TRPM8 channel in the treatment of OAB. Validation experiments confirmed the interaction between Rhy and these targets. Additionally, the GeneCards database predicted other targets that are not directly linked to OAB, corroborated by the literature. Conclusions: We established a more accurate and comprehensive dataset of OAB targets, enhancing the reliability of target identification for drug treatments. This study underscores the importance of database quality in network pharmacology and contributes to the potential therapeutic strategies for OAB.

Background: Arthritis, a debilitating joint disease, remains a significant global health burden. This study uncovers the therapeutic potential of the medicinal plant Smilax glabra Roxb. (SGR) in attenuating progression of disease by modulating immune responses. Methods: Through computational approaches, key bioactive compounds in SGR were identified by using freely available databases: TCMSP, TCMID, HIT2.0, HERB, and INPUT in order to elucidate their underlying mechanisms of action. Therapeutic targets for the disease have been retrieved by TTD, GeneCard, and OMIM databases. The STRING database was used to analyze the protein–protein interactions (PPI) of intersecting genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to reveal the functional roles of genes. Mcule was used for molecular docking and binding affinity of compounds and targets were evaluated by DeepPurpose model. ALP activity, cell viability assay, TRAP staining were also performed. Results: A total of 14 active SGR compounds with 59 common targets for arthritis have been identified. These targets have a major role in controlling biological processes such as wound healing, oxygen responses, and chemical stimuli. Molecular docking by Mcule platform demonstrated that quercetin and β-sitosterol showed higher binding energy affinities with TNF, TP53, PTGS2, and JUN as compared to other targets. To explore the complex relationship between compounds and targets, pre-trained Davis and KIBA models were used to predict the affinity values of selected compounds. In MC3T3-E1 cells, ALP activity was significantly increased and bone marrow macrophages (BMM) showed a low number of TRAP-positive cells in SGR-treated cells. Conclusions: Our findings demonstrate that SGR effectively inhibits/regulates inflammatory responses, prevents cartilage degradation, promotes bone regeneration, and can be used as a promising candidate for the development of novel arthritis treatment.

Background: Polygonum orientale L. (PO) has demonstrated notable efficacy in treating coronary heart disease. Previous research identified eight key active components in PO for cardiomyocyte protection, but the underlying mechanisms remained unclear; Methods: Network pharmacology and molecular docking were used to identify potential target proteins of PO’s active components. Experimental models assessed the cardioprotective effects and mechanisms; Results: Network analysis and molecular docking revealed that the active components exhibited the highest binding affinity with SOD2, indicating it as a key element in the cardiac protection of PO. In vivo, PO extract improved myocardial structure and function, and increased SOD2 protein levels. In vitro, the active components of PO (Mixture) mitigated oxidative stress and apoptosis, upregulating SIRT3 and decreasing acetylated SOD2, leading to increased SOD2 and reduced ROS levels. The observed effects were reversed by a SIRT3 inhibitor, indicating the involvement of the SIRT3/SOD2 signaling pathway; Conclusions: This comprehensive approach elucidated the critical mechanisms underlying the cardioprotective properties of PO’s bioactive constituents, highlighting the regulation of the SIRT3/SOD2 signaling pathway as a new mechanism for PO’s anti-cardiovascular disease effects, and suggesting the Mixture’s potential as a promising drug candidate.

Dendrobium officinale flowers (DOF) have previously been established as a promising source of natural antioxidants, and it is ideally suited for processing to prepare functional foods and food additives. The precise extraction processes employed, however, can alter the composition and antioxidant properties of the resultant products, and the characteristic compounds associated with the active fractions prepared from DOF or their mechanisms of action have yet to be reported. To clarify the molecular mechanisms through which these active fractions function for the first time, chromatography was used to separate DOF extracts, yielding five fractions (Fr. (a—e)). Analyses of the antioxidant activity for these different fractions revealed that Fr. (d) presented with the most robust bioactivity. Levels of total flavonoids were then measured, revealing that antioxidant activity levels were positively correlated with total flavonoid content. Fr. (d) was found to contain 20 flavonoids in HPLC-Triple-TOF-MS/MS analyses. At the cellular level, Fr. (d) was found to induce increases in the levels of protective antioxidant factors (SOD and GSH-Px) while reducing the levels of reactive oxygen species (ROS), damage-associated factors (MDA, NO, TNF-α, IL-1β, and IL-6), and inducible nitric oxide synthase (iNOS) expression in C2C12 cells that had been stimulated with H2O2. These data thus provided support for Fr. (d) prevention of oxidative stress and inflammation. Network pharmacology analyses further suggested that Fr. (d) can help protect against oxidative stress through its effects on PI3K/Akt-related signaling activity. Fr. (d) was subsequently found to upregulate PI3K/Akt pathway-related proteins, nuclear transcription factor 2 (Nrf2), and heme oxygenase 1 (HO-1) in addition to suppressing Kelch-like epoxide-related protein 1 (Keap1) expression. In summary, Fr. (d) was found to suppress PI3K/Akt/Nrf2 pathway activation, ultimately alleviating inflammation and oxidative stress as predicted with a network pharmacology approach. Future studies aimed at clarifying the composition and mechanistic activity of DOF Fr. (d) will likely help establish it as a functional food capable of promoting health and longevity.

The occurrence of type 2 diabetes mellitus (T2DM), a worldwide chronic disease, is mainly caused by insufficient insulin production and places a huge burden on the health system. Gastrodia elata Blume (GE), a food of medicine–food homology, has been reported to have the ability to inhibit glycosidase activity, indicating its potential in the treatment of diabetes. However, the main pharmacological components of GE for the treatment of T2DM have not been fully clarified. Therefore, this study aims to clarify the pharmacological components changes of GE with different drying methods and the treatment of T2DM using HPLC, network pharmacology, molecular docking and experimental evaluations. The results showed that the GE samples processed by the steam-lyophilized method possessed the highest total content of the six marker components and the strongest antioxidant and α-glucosidase inhibitory abilities. Meanwhile, the six marker compounds had a total of 238 T2DM-related gene targets. Notably, these active compounds have good affinity for key gene targets associated with T2DM signaling pathways. In conclusion, this study revealed that different drying methods of GE affect the content of its major active compounds, antioxidant capacity, α-glucosidase inhibitory capacity and potential pharmacological effects on T2DM, indicating that it is a potential treatment of T2DM.

In the present study, a series of coumarins, including eight undescribed bis-isoprenylated ones Spinifoliumin A-H, were isolated and identified from the aerial parts of Zanthoxylum dimorphophyllum var. spinifolium (ZDS), a plant revered in traditional Chinese medicine, particularly for treating rheumatoid arthritis (RA). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy, complemented by ECD, [Rh2(OCOCF3)4]-induced ECD, Mo2(OAc)4 induced ECD, IR, and HR-ESI-MS mass spectrometry. A network pharmacology approach allowed for predicting their anti-RA mechanisms and identifying the MAPK and PI3K-Akt signaling pathways, with EGFR as a critical gene target. A CCK-8 method was used to evaluate the inhibition activities on HFLS-RA cells of these compounds. The results demonstrated that Spinifoliumin A, B, and D-H are effective at preventing the abnormal proliferation of LPS-induced HFLS-RA cells. The results showed that compounds Spinifoliumin A, D, and G can significantly suppress the levels of IL-1β, IL-6, and TNF-α. Moreover, molecular docking methods were utilized to confirm the high affinity between Spinifoliumin A, D, and G and EGFR, SRC, and JUN, which were consistent with the results of network pharmacology. This study provides basic scientific evidence to support ZDS’s traditional use and potential clinical application.

Agarwood, a precious traditional medicinal herb and fragrant material, is known for its sedative and sleep-improving properties. This study explores the mechanisms underlying the aromatherapy effects of Chi-Nan agarwood and ordinary agarwood in improving sleep. Using a combination of gas chromatography–mass spectrometry (GC-MS), network pharmacology, and molecular docking techniques, we identified and c ompared the chemical compositions and potential molecular targets of both types of agarwood. The GC-MS analysis detected 87 volatile components across six types of agarwood aromatherapy, with 51 shared between Chi-Nan and ordinary agarwood, while each type also had 18 unique components. Ordinary agarwood was found to be richer in sesquiterpenes and small aromatic molecules, whereas Chi-Nan agarwood contained higher levels of chromones. These differences in chemical composition are likely responsible for the distinct sleep-improving effects observed between the two types of agarwood. Through network pharmacology, 100, 65, and 47 non-repetitive target genes related to sleep improvement were identified for components shared by both types of agarwood (CSBTs), components unique to common agarwood (CUCMs), and components unique to Chi-Nan agarwood (CUCNs), respectively. The constructed protein–protein interaction (PPI) networks revealed that key targets such as MAOA, MAOB, SLC6A4, and ESR1 are involved in the sleep-improving mechanisms of agarwood aromatherapy. Molecular docking further confirmed the strong binding affinities of major active components, such as 5-Isopropylidene-6-methyldeca-369-trien-2-one and 2-(2-Phenylethyl)chromone, with these core targets. The results suggest that agarwood aromatherapy enhances sleep quality through both hormonal and neurotransmitter pathways, with ordinary agarwood more deeply mediating hormonal regulation, while Chi-Nan agarwood predominantly influences neurotransmitter pathways, particularly those involving serotonin and GABA. This study provides valuable insights into the distinct therapeutic potentials of Chi-Nan and ordinary agarwood, highlighting their roles in sleep improvement and offering a foundation for future research in the clinical application of agarwood-based aromatherapy.

Torreya grandis (T. grandis, Taxaceae) is a well-known nut tree species. Its fruit aril and leaves possess a unique aroma, making it an ideal natural raw material for extracting essential oils (EOs). This study aims to comprehensively compare the composition, biological activities, and pharmacological mechanism of EOs extracted from the arils (AEO) and leaves (LEO) of T. grandis. The results revealed that the chemical composition of the two EOs was highly consistent, with α-pinene and D-limonene as the main components. Both EOs significantly reduced cellular melanin production and inhibited tyrosinase activity in α-MSH-stimulated B16 cells (p < 0.05). AEO and LEO suppressed inflammatory responses in LPS-stimulated RAW 264.7 macrophages, significantly inhibiting cellular NO production and proinflammatory cytokines such as TNF-α and IL-6 (p < 0.05). A network pharmacology analysis reveals that AEO and LEO share similar molecular mechanisms and pharmacological pathways for treating skin pigmentation and inflammation. Regulating inflammatory cytokines may be a critical pathway for AEO and LEO in treating skin pigmentation. These findings suggest that AEO and LEO have potential for cosmetic applications. The leaves of T. grandis could be a valuable source of supplementary materials for producing T. grandis aril EO.

The seeds of ginkgo biloba L (GB) have been widely used worldwide. This study investigated the bioefficacies of whole GB seed powder (WGP) retaining the full nutrients of ginkgo against aging, atherosclerosis, and fatigue. The experimental results indicated that WGP lowered brain monoamine oxidase and serum malondialdehyde levels, enhanced thymus/spleen indexes, and improved learning ability, and delayed aging in senescent mice. WGP regulated lipid levels and prevented atherosclerosis by reducing triglycerides, lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and decreasing the atherosclerosis index. WGP improved exercise performance by reducing blood lactate accumulation and extending exhaustive swimming and climbing times, improved energy storage by increasing muscle/liver glycogen levels, and relieved physical fatigue. Network pharmacology analysis revealed 270 potential targets of WGP that play roles in cellular pathways related to inflammation inhibition, metabolism regulation, and anti-cellular senescence, etc. Protein-protein interaction analysis identified 10 hub genes, including FOS, ESR1, MAPK8, and SP1 targets. Molecular docking and molecular dynamics simulations showed that the bioactive compounds of WGP bound well to the targets. This study suggests that WGP exerts prominent health-promoting effects through multiple components, targets, and pathways.

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.

(1) Background: Diabetic retinopathy (DR) is a major complication of diabetes, marked by abnormal angiogenesis, microaneurysms, and retinal hemorrhages. Traditional Ayurvedic medicine advocates multi-target strategies for DR management. However, the mechanisms by which Solanum xanthocarpum (SX) and Plumbago zeylanica (PZ) exert therapeutic effects are not well understood; (2) Methods: To investigate these mechanisms, we employed network pharmacology and molecular docking techniques. Phytochemicals from SX and PZ were identified using the IMPPAT database and Swiss Target Prediction tool. DR-related protein targets were sourced from the GeneCards database, and common targets were identified through Venn diagram analysis. STRING and Cytoscape were used to construct and analyze protein–protein interaction networks. Pathway enrichment was performed with Gene Ontology and KEGG databases; (3) Results: We identified 28 active phytoconstituents, targeting proteins such as EGFR, SRC, STAT3, AKT1, and HSP90AA1. Molecular docking and dynamics simulations confirmed the strong binding affinities of these compounds to their targets; (4) Conclusions: The study highlights the multi-target activity of SX and PZ, particularly in pathways related to EGFR tyrosine kinase inhibitor resistance and PI3K–AKT signaling. These findings provide valuable insights into their therapeutic potential for DR, suggesting the effective modulation of key molecular pathways involved in the disease.

Feline infectious peritonitis (FIP), a serious infectious disease in cats, has become a challenging problem for pet owners and the industry due to the lack of effective vaccinations and medications for prevention and treatment. Currently, most natural compounds have been proven to have good antiviral activity. Hence, it is essential to develop efficacious novel natural compounds that inhibit FIPV infection. Our study aimed to screen compounds with in vitro anti-FIPV effects from nine natural compounds that have been proven to have antiviral activity and preliminarily investigate their mechanisms of action. In this study, the CCK-8 method was used to determine the maximum noncytotoxic concentration (MNTC), 50% cytotoxic concentration (CC50), and 50% effective concentration (EC50) of natural compounds on CRFK cells and the maximum inhibition ratio (MIR) of the compounds inhibit FIPV. The effect of natural compounds on FIPV-induced apoptosis was detected via Annexin V-FITC/PI assay. Network pharmacology (NP), molecular docking (MD), and 4D label-free quantitative (4D-LFQ) proteomic techniques were used in the joint analysis the mechanism of action of the screened natural compounds against FIPV infection. Finally, Western blotting was used to validate the analysis results. Among the nine natural compounds, baicalin had good antiviral effects, with an MIR > 50% and an SI > 3. Baicalin inhibited FIPV-induced apoptosis. NP and MD analyses showed that AKT1 was the best target of baicalin for inhibiting FIPV infection. 4D-LFQ proteomics analysis showed that baicalin might inhibit FIPV infection by modulating the PI3K-AKT pathway and the apoptosis pathway. The WB results showed that baicalin promoted the expression of EGFR, PI3K, and Bcl-2 and inhibited the expression of cleaved caspase 9 and Bax. This study found that baicalin regulated the PI3K-AKT pathway and the apoptosis pathway in vitro and inhibited FIPV-induced apoptosis, thus exerting anti-FIPV effects.

Renovascular hypertension (RH), a secondary hypertension, can significantly impact heart health, resulting in heart damage and dysfunction, thereby elevating the risk of cardiovascular diseases. Coniferol (CA), which has vascular relaxation properties, is expected to be able to treat hypertension-related diseases. However, its potential effects on cardiac function after RH remain unclear. In this study, in combination with network pharmacology, the antihypertensive and cardioprotective effects of CA in a two-kidney, one-clip (2K1C) mice model and its ability to mitigate angiotensin II (Ang II)-induced hypertrophy in H9C2 cells were investigated. The findings revealed that CA effectively reduced blood pressure, myocardial tissue damage, and inflammation after RH. The possible targets of CA for RH treatment were screened by network pharmacology. The interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathways were identified using a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The inflammatory response was identified using a Gene Ontology (GO) enrichment analysis. Western blot analysis confirmed that CA reduced the expression of IL-17, matrix metallopeptidase 9 (MMP9), cyclooxygenase 2 (COX2), and TNF α in heart tissues and the H9C2 cells. In summary, CA inhibited cardiac inflammation and fibrohypertrophy following RH. This effect was closely linked to the expression of MMP9/COX2/TNF α/IL-17. This study sheds light on the therapeutic potential of CA for treating RH-induced myocardial hypertrophy and provides insights into its underlying mechanisms, positioning CA as a promising candidate for future drug development.

Herbs, such as Aconitum carmichaeli Debeaux (ACD), have long been used as therapies, but it is difficult to identify which organs of the human body are affected by the various compounds. In this study, we predicted the organ where the drug predominantly acts using bioinformatics and verified it using transcriptomics. We constructed a computer-aided brain system network (BSN) and intestinal system network (ISN). We predicted the action points of ACD using network pharmacology (NP) analysis and predicted the dockable proteins acting in the BSN and ISN using statistical-based docking analysis. The predicted results were verified using ACD-induced transcriptome analysis. The predicted results showed that both the NP and docking analyses predominantly acted on the BSN and showed better hit rates in the hub nodes. In addition, we confirmed through verification experiments that the SW1783 cell line had more than 10 times more differentially expressed genes than the HT29 cell line and that the dominant acting organ is the brain, using network dimension spanning analysis. In conclusion, we found that ACD preferentially acts in the brain rather than in the intestine, and this multi-bioinformatics-based approach is expected to be used in future studies of drug efficacy and side effects.

Hyperlipidemia is a metabolic disorder characterized by abnormal lipid metabolism, resulting in lipid accumulation in the plasma. According to reports, medicinal and edible plants can reduce the risk of metabolic diseases such as hyperlipidemia. This study investigates the effects and mechanisms of Astragalus membranaceus extract (AME), Hippophae rhamnoides L. extract (HRE), and Taraxacum mongolicum Hand. Mazz extract (TME) on hyperlipidemia. Active compounds and potential gene targets of AME, HRE, and TME were screened using LC-MS and TCMSP databases, and hyperlipidemia targets were detected from the OMIM and DisGeNet databases. A drug-target pathway disease network was constructed through protein interactions, GO enrichment, and KEGG pathway analysis. Finally, the lipid-lowering effects of three extracts were validated through in vitro HepG2 cell and in vivo animal experiments. The results show that LC-MS and network pharmacology methodologies identified 41 compounds and 140 targets. KEGG analysis indicated that the PI3K-Akt and MAPK signaling pathways significantly treat hyperlipidemia with AHT. In vitro experiments have shown that AHT is composed of a ratio of AME:HRE:TME = 3:1:2. HepG2 cell and animal experiments revealed that AHT exhibits strong lipid-lowering and antioxidant properties, significantly regulating the levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC). It is worth noting that AHT can effectively downregulate the protein expression levels of p-AKT/AKT and p-PI3K/PI3K and upregulate the protein expression levels of p-AMPK/AMPK and SIRT1, verifying the results predicted by network pharmacology. This study presents a novel approach to utilizing these natural plant extracts as safe and effective treatments for hyperlipidemia.

The incidence of type 2 diabetes (T2D) is rising, and finding new treatments is important. C. sativa is a plant suggested as a potential treatment for T2D, but how it works needs to be clarified. This study explored the pharmacological mechanism of C. sativa in treating T2D. We identified the active compounds in C. sativa and their targets. From there, we examined the genes associated with T2D and found overlapping genes. We conducted an enrichment analysis and created a protein–protein and target–compound interactions network. We confirmed the binding activities of the hub proteins and compounds with molecular docking. We identified thirteen active compounds from C. sativa, which have 150 therapeutic targets in T2D. The enrichment analysis showed that these proteins are involved in the hormone, lipid, and stress responses. They bind transcription factors and metals and participate in the insulin, PI3K/Akt, HIF-1, and FoxO signaling pathways. We found four hub proteins (EGFR, ESR1, HSP90AA1, and SRC) that bind to the thirteen bioactive compounds. This was verified using molecular docking. Our findings suggest that C. sativa’s antidiabetic action is carried out through the insulin signaling pathway, with the participation of HIF-1 and FoxO.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD. The livers of patients with NASH are more likely to develop fibrosis. Xiaoyao San (XYS) is a classic traditional Chinese medicine (TCM) formula that has been widely used in treating liver diseases. In this study, we elucidated the effects and mechanism of XYS in treating NASH-related liver fibrosis by combining high-throughput sequencing-based high-throughput screening with network pharmacology analysis. Our work revealed that XYS may play a role in preventing NASH-related liver fibrosis by regulating biological functions related to the extracellular matrix (ECM), inflammation, and metabolism. Additionally, Bupleuri Radix, Poria, Zingiberis Rhizoma Recens, and Paeoniae Radix Alba are the key herbs of XYS that could partially represent the functions of XYS. These regulatory effects are mediated by targeting signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NFκB), and peroxisome proliferator-activated receptor gamma (PPARγ) signaling. Narcissin, casuarictin, and γ-sitosterol were identified as representative active compounds in XYS targeting STAT3, NFκB, and PPARγ, respectively. Taken together, our findings provide a novel strategy for investigating the pharmacological effects and biological mechanisms of a TCM formula.

Fuzheng Xiaozheng prescription (FZXZP) is an effective formula for the treatment of different kinds of chronic liver diseases. However, its potential molecular mechanisms in treating hepatocellular carcinoma (HCC) have not been investigated thoroughly. The aim of this study is to elucidate the targets and intrinsic mechanisms of FZXZP and their active components for the treatment of HCC. The efficacy of FZXZP against HCC was clarified through a rat HCC model and HCC cell culture. Network pharmacology and molecular docking were utilized to predict the mechanism of action and effector components of FZXZP. The key mechanism and targets were verified by the construction of overexpression and knockout cell models. The results showed that FZXZP greatly delayed the development of HCC in vivo experiments, as evidenced by biochemical evaluations, H&E analyses and growth inhibition of HCC. FZXZP dramatically inhibited cell viability and proliferative capacity and induced the apoptosis of hepatoma cells in vitro. Moreover, network pharmacology analyses demonstrated that the EGFR family and apoptosis-related targets were found to be the most significant in bioinformatics analysis. Furthermore, the EGFR/STAT3 signal axis might be the most likely target of FZXZP in anti-HCC due to the fact that it could be down-regulated by FZXZP with an upward trend of Bax, Caspase-3, Caspase-8, Caspase-9 and an inverse trend of Bcl2. Importantly, the above targeted signal axis was finally validated by our knockdown and overexpression analyses. Meanwhile, flow cytometry and TUNEL staining also revealed that FZXZP significantly induced apoptosis in the EGFR-overexpressing HCC cell line. The molecular docking results revealed that the key effector components of FZXZP that exerted the above regulatory roles were wogonin and glycitein. All of these results suggest that FZXZP could significantly delay HCC development by inhibiting proliferation and promoting apoptosis of HCC cells, and the EGFR/STAT3 signal axis might be a critical signal axis of FZXZP in suppressing HCC progression.

Necrotic enteritis (NE) is a critical disease affecting broiler health, with Clostridium perfringens as its primary pathogen. Polygonum hydropiper compound extract (PHCE), formulated based on traditional Chinese veterinary principles, contains primarily flavonoids with antibacterial, anti-inflammatory, and antioxidant properties. However, PHCE’s efficacy against Clostridium perfringens-induced NE and its underlying mechanism remain unclear. This study employed network pharmacology and molecular docking to predict PHCE’s potential mechanisms in treating NE, followed by determining its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Clostridium perfringens (C. perf). Subsequently, the effects of various PHCE doses on intestinal damage, antioxidant capacity, and inflammatory factors in C. perf-infected broilers were assessed. Network pharmacology and molecular docking suggested that PHCE’s therapeutic mechanism for NE involves the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome signaling pathway, with flavonoids such as quercetin, kaempferol, and isorhamnetin as key active components. PHCE exhibited an MIC of 3.13 mg/mL and an MBC of 12.5 mg/mL against C. perf. High PHCE doses effectively reduced intestinal damage scores in both the jejunum and ileum, accompanied by attenuated intestinal pathological changes. Additionally, the high dose significantly increased superoxide dismutase (SOD) levels while decreasing malondialdehyde (MDA), hydrogen peroxide (H2O2), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in the jejunum and ileum (p < 0.01 or p < 0.05). PHCE also modulated the expression of caspase-1, IL-1β, gasdermin D (GSDMD), and NLRP3 mRNA, key components of the NLRP3 inflammasome signaling pathway, in both intestinal segments. These findings collectively indicate that PHCE protects against C. perf-induced oxidative stress and inflammatory damage in NE. By enhancing antioxidant capacity, PHCE likely reduces oxidative stress and inflammatory responses, subsequently modulating NLRP3 inflammasome signaling pathway key factor expression. Overall, this research provides valuable insights into the protective mechanism of the herbal compound PHCE and its potential benefits for avian health.

Catechins, a class of polyphenolic compounds found in tea, have attracted significant attention due to their numerous health benefits, particularly for the treatment and protection of hypertension. However, the potential targets and mechanisms of action of catechins in combating hypertension remain unclear. This study systematically investigates the anti-hypertensive mechanisms of tea catechins using network pharmacology, molecular docking, and molecular dynamics simulation techniques. The results indicate that 23 potential anti-hypertensive targets for eight catechin components were predicted through public databases. The analysis of protein–protein interaction (PPI) identified three key targets (MMP9, BCL2, and HIF1A). KEGG pathway and GO enrichment analyses revealed that these key targets play significant roles in regulating vascular smooth muscle contraction, promoting angiogenesis, and mediating vascular endothelial growth factor receptor signaling. The molecular docking results demonstrate that the key targets (MMP9, BCL2, and HIF1A) effectively bind with catechin components (CG, GCG, ECG, and EGCG) through hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations further confirmed the stability of the binding between catechins and the targets. This study systematically elucidates the potential mechanisms by which tea catechins treat anti-hypertension and provides a theoretical basis for the development and application of tea catechins as functional additives for the prevention of hypertension.

Chemotherapy-induced diarrhea (CID) is a potentially serious side effect that often occurs during anticancer therapy and is caused by the toxic effects of chemotherapeutic drugs on the gastrointestinal tract, resulting in increased frequency of bowel movements and fluid contents. Among these agents, irinotecan (CPT-11) is most commonly associated with CID. Hesperidin (HPD), a flavonoid glycoside found predominantly in citrus fruits, has anti-oxidation properties and anti-inflammation properties that may benefit CID management. Nevertheless, its potential mechanism is still uncertain. In this study, we firstly evaluated the pharmacodynamics of HPD for the treatment of CID in a mouse model, then used network pharmacology and molecular docking methods to excavate the mechanism of HPD in relieving CID, and finally further proved the predicted mechanism through molecular biology experiments. The results demonstrate that HPD significantly alleviated diarrhea, weight loss, colonic pathological damage, oxidative stress, and inflammation in CID mice. In addition, 74 potential targets for HPD intervention in CID were verified by network pharmacology, with the top 10 key targets being AKT1, CASP3, ALB, EGFR, HSP90AA1, MMP9, ESR1, ANXA5, PPARG, and IGF1. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the PI3K–Akt pathway, FoxO pathway, MAPK pathway, TNF pathway, and Ras pathway were most relevant to the HPD potential treatment of CID genes. The molecular docking results showed that HPD had good binding to seven apoptosis-related targets, including AKT1, ANXA5, CASP3, HSP90AA1, IGF1, MMP9, and PPARG. Moreover, we verified apoptosis by TdT-mediated dUTP nick-end labeling (TUNEL) staining and immunohistochemistry, and the hypothesis about the proteins above was further verified by Western blotting in vivo experiments. Overall, this study elucidates the potential and underlying mechanisms of HPD in alleviating CID.

Diabetic nephropathy (DN) is one of the common complications of diabetes and the main cause of end-stage renal disease (ESRD) in clinical practice. Schisandrin A (Sch A) has multiple pharmacological activities, including inhibiting fibrosis, reducing apoptosis and oxidative stress, and regulating immunity, but its pharmacological mechanism for the treatment of DN is still unclear. In vivo, streptozotocin (STZ) and a high-fat diet were used to induce type 2 diabetic rats, and Sch A was administered for 4 weeks. At the same time, protein–protein interaction (PPI) networks were established to analyze the overlapping genes of DN and Sch A. Subsequently, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to determine the hub pathway. In addition, molecular docking was used to preliminarily verify the affinity of hub proteins and Sch A. Further, H&E staining, Sirius red staining, immunohistochemistry, immunofluorescence, and western blot analysis were used to detect the location and expression of related proteins in DN. This study revealed the multi-target and multi-pathway characteristics of Sch A in the treatment of DN. First, Sch A could effectively improve glucose tolerance, reduce urine microprotein and urine creatinine levels, and alleviate renal pathological damage in DN rats. Second, EGFR was the hub gene screened in overlapping genes (43) of Sch A (100) and DN (2524). Finally, it was revealed that Sch A could inhibit the protein expression levels of EGFR and PTRF and reduced the expression of apoptosis-related proteins, and this effect was related to the modulation of the AKT/GSK-3β signaling pathway. In summary, Sch A has a protective effect in DN rats, EGFR may be a potential therapeutic target, throughout modulating AKT/GSK-3β pathway.

Purpose: This study aims to explore the potential mechanisms of esculin in the treatment of renal cell carcinoma (RCC). Methods: We employed network pharmacology to predict the potential mechanisms and targets of esculin in RCC. Molecular docking techniques were then employed to validate the predicted targets. Additionally, a series of in vitro experiments were conducted to verify the anticancer effects of esculin on RCC cells, including the CCK-8 assay, EdU assay, wound healing assay, apoptosis assay, and Western blot. Results: Network pharmacology and molecular docking results identified GAPDH, TNF, GSK3B, CCND1, MCL1, IL2, and CDK2 as core targets. GO and KEGG analyses suggested that esculin may influence apoptotic processes and target the PI3K/Akt pathway in RCC. Furthermore, the CCK-8 assay demonstrated that esculin inhibited RCC cell viability. Microscopic observations revealed that following esculin treatment, there was an increase in cell crumpling, a reduction in cell density, and an accumulation of floating dead cells. Additionally, with increasing esculin concentrations, the proportion of EdU-positive cells decreased, the wound closure ratio decreased, the proportion of PI-positive cells increased, the expression levels of BAX and cleaved-caspase-3 proteins increased, and the expression level of Bcl2 protein decreased. These findings suggested that esculin inhibits the proliferation and migration of RCC cells while promoting apoptosis. Moreover, esculin was found to target GAPDH and inhibit the PI3K/Akt pathway. Conclusions: This study is the first to elucidate the therapeutic effects of esculin on RCC cells. The results provide evidence supporting the clinical application of esculin and introduce a promising new candidate for RCC treatment.

Allergic rhinitis (AR) is a series of allergic reactions to allergens in the nasal mucosa and is one of the most common allergic diseases that affect both children and adults. Shi-Bi-Lin (SBL) is the modified formula of Cang Er Zi San (CEZS), a traditional Chinese herbal formula used for treating AR. Our study aims to elucidate the anti-inflammatory effects and mechanisms of SBL in house dust mite-induced AR by regulating gut microflora metabolism. In vivo studies showed that nasal allergies and the infiltration of inflammatory cells in the nasal epithelium were significantly suppressed by SBL. Moreover, SBL restored the impaired nasal epithelial barrier function with an increased tight junction protein expression and reduced the endothelial nitric oxide synthase (eNOS). Interestingly, SBL significantly reconstituted the abundance and composition of gut microbiota in AR mice; it increased the relative abundance of potentially beneficial genera and decreased the relative abundance of harmful genera. SBL also restored immune-related metabolisms, which were significantly increased and correlated with suppressing inflammatory cytokines. Furthermore, a network analysis and molecular docking indicated IL-6 was a possible target drug candidate for the SBL treatment. SBL dramatically reduced the IL-6 level in the nasal lavage fluid (NALF), suppressing the IL-6 downstream Erk1/2 and AKT/PI3K signaling pathways. In conclusion, our study integrates 16S rRNA sequencing, microflora metabolism, and network pharmacology to explain the immune mechanism of SBL in alleviating HDM-induced allergic rhinitis.

The inhibition of dipeptidyl peptidase-IV (DPP-IV) is a promising approach for regulating the blood glucose levels in patients with type 2 diabetes (T2D). Oysters, rich in functional peptides, contain peptides capable of inhibiting DPP-IV activity. This study aims to identify the hypoglycemic peptides from oysters and investigate their potential anti-T2D targets and mechanisms. This research utilized virtual screening for the peptide selection, followed by in vitro DPP-IV activity assays to validate the chosen peptide. Network pharmacology was employed to identify the potential targets, GO terms, and KEGG pathways. Molecular docking and molecular dynamics simulations were used to provide virtual confirmation. The virtual screening identified LRGFGNPPT as the most promising peptide among the screened oyster peptides. The in vitro studies confirmed its inhibitory effect on DPP-IV activity. Network pharmacology revealed that LRGFGNPPT exerts an anti-T2D effect through multiple targets and signaling pathways. The key hub targets are AKT1, ACE, and REN. Additionally, the molecular docking results showed that LRGFGNPPT exhibited a strong binding affinity with targets like AKT1, ACE, and REN, which was further confirmed by the molecular dynamics simulations showcasing a stable peptide–target interaction. This study highlights the potential of LRGFGNPPT as a natural anti-T2D peptide, providing valuable insights for potential future pharmaceutical or dietary interventions in T2D management.

Prior studies have extensively investigated the essential oil derived from the Mediterranean cypress, Cupressus sempervirens. However, the ‘Stricta’ variety, known for its ornamental value, has received less attention in terms of its oil composition and potential health benefits. The objective of this research was to comprehensively analyze the chemical components and medicinal properties of the essential oil extracted from C. sempervirens ‘Stricta’ (CSSLEO) grown in Egypt. Utilizing gas chromatography–mass spectrometry (GC–MS), the investigation identified 22 compounds within CSSLEO, with α-pinene and δ-3-carene being predominant, accounting for 96.01% of the oil. In vitro assays evaluated CSSLEO’s cytotoxic effects on cancer cell lines, revealing notable anticancer potential. Additionally, the oil displayed antidiabetic properties by impeding crucial enzymes involved in glucose metabolism. Complementary in silico network pharmacology and molecular docking studies provided insights into the possible interactions between CSSLEO’s key compounds and essential proteins and pathways in cancer treatment. The results underscored CSSLEO’s intricate composition and its promising applications in cancer prevention and diabetes management. The conclusions drawn from this research underscore the need for further investigation to validate CSSLEO’s clinical effectiveness and to gain a deeper understanding of its therapeutic mechanisms, with a view to harnessing its potential in oncology and endocrinology.

Down Syndrome (DS), characterized by trisomy of chromosome 21, leads to the overexpression of several genes contributing to various pathologies, including cognitive deficits and early-onset Alzheimer’s disease. This study aimed to identify the intersection genes of two polyphenolic compounds, apigenin and naringenin, and their potential therapeutic targets in DS using network pharmacology. Key proteins implicated in DS, comprising DYRK1A, APP, CBS, and ETS2, were selected for molecular docking and dynamics simulations to assess the binding affinities and stability of the protein–ligand interactions. Molecular docking revealed that naringenin exhibited the highest binding affinity to DYRK1A with a score of −9.3 kcal/mol, followed by CBS, APP, and ETS2. Moreover, molecular docking studies included positive control drugs, such as lamellarin D, valiltramiprosate, benserazide, and TK216, which exhibited binding affinities ranging from −5.5 to −8.9 kcal/mol. Apigenin showed strong binding to APP with a score of −8.8 kcal/mol, suggesting its potential in modulating amyloid-beta levels. These interactions were further validated through molecular dynamics simulations, demonstrating stable binding throughout the 100 ns simulation period. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses indicated minimal fluctuations, confirming the stability of the complexes. The findings suggest that apigenin and naringenin could serve as effective therapeutic agents for DS by targeting key proteins involved in its pathology. Future studies should focus on in vivo validation, clinical trials, and exploring combination therapies to fully harness the therapeutic potential of these compounds for managing DS. This study underscores the promising role of network pharmacology in identifying novel therapeutic targets and agents for complex disorders like DS.

The objective of this study was to elucidate the mechanism of action of the active components of Coptidis rhizoma against porcine epidemic diarrhea and to provide a theoretical foundation for further development of novel anti-PED therapeutic agents based on Coptidis rhizoma. The potential targets of Coptidis rhizoma against PEDV were identified through a comprehensive literature review and analysis using the TCMSP pharmacological database, SwissDrugDesign database, GeneCards database, and UniProt database. Subsequently, the STRING database and Cytoscape 3.7.1 software were employed to construct a protein–protein interaction (PPI) network and screen key targets. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted on the identified targets. Molecular docking studies were performed using AutoDock 1.5.7 software to analyze the binding energy and modes of interaction between the active components of Coptidis rhizoma and the target proteins. The PyMOL 2.5.0a0 software was employed to visualize the docking results. Through comprehensive analysis, 74 specific targets of active components of Coptidis rhizoma against PEDV were identified. The core gene targets were screened, and an interaction network diagram was subsequently generated. Ultimately, 14 core targets were identified, with STAT3, ESR1, CASP3, and SRC exhibiting the most significant interactions. GO enrichment analysis revealed a total of 215 molecular items, including 48 biological function items, 139 biological process items, and 28 cellular component items. KEGG enrichment analysis identified 140 signaling pathways. Molecular docking analysis demonstrated that epiberberine and palmatine exhibited high binding affinity with STAT3 protein, worenine showed high binding affinity with ESR1 protein, obacunone exhibited high binding affinity with CASP3 protein, and epiberberine, obacunone, berberine, and berberruine exhibited high binding affinity with SRC protein. A network pharmacology and molecular docking technology approach was employed to screen six important active components of Coptidis rhizoma and four important potential targets against PEDV infection. The findings indicated that the active components of Coptidis rhizoma could serve as promising pharmaceutical agents for the prevention and control of PEDV, with significant potential for clinical application.

Background: Resveratrol is a potent phytochemical known for its potential in treating cardiometabolic multimorbidity. However, its underlying mechanisms remain unclear. Our study systematically investigates the effects of resveratrol on cardiometabolic multimorbidity and elucidates its mechanisms using network pharmacology and molecular docking techniques. Methods: We screened cardiometabolic multimorbidity-related targets using the OMIM, GeneCards, and DisGeNET databases, and utilized the DSigDB drug characterization database to predict resveratrol’s effects on cardiometabolic multimorbidity. Target identification for resveratrol was conducted using the TCMSP, SymMap, DrugBank, Swiss Target Prediction, CTD, and UniProt databases. SwissADME and ADMETlab 2.0 simulations were used to predict drug similarity and toxicity profiles of resveratrol. Protein–protein interaction (PPI) networks were constructed using Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed via the DAVID online platform, and target-pathway networks were established. Molecular docking validated interactions between core targets and resveratrol, followed by molecular dynamics simulations on the optimal core proteins identified through docking. Differential analysis using the GEO dataset validated resveratrol as a core target in cardiometabolic multimorbidity. Results: A total of 585 cardiometabolic multimorbidity target genes were identified, and the predicted results indicated that the phytochemical resveratrol could be a major therapeutic agent for cardiometabolic multimorbidity. SwissADME simulations showed that resveratrol has potential drug-like activity with minimal toxicity. Additionally, 6703 targets of resveratrol were screened. GO and KEGG analyses revealed that the main biological processes involved included positive regulation of cell proliferation, positive regulation of gene expression, and response to estradiol. Significant pathways related to MAPK and PI3K-Akt signaling pathways were also identified. Molecular docking and molecular dynamics simulations demonstrated strong interactions between resveratrol and core targets such as MAPK and EGFR. Conclusions: This study predicts potential targets and pathways of resveratrol in treating cardiometabolic multimorbidity, offering a new research direction for understanding its molecular mechanisms. Additionally, it establishes a theoretical foundation for the clinical application of resveratrol.

The current research employed an animal model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland carcinogenesis. The estrogen receptor-positive human breast adenocarcinoma cell line (MCF-7) was used for in vitro analysis. This was combined with a network pharmacology-based approach to assess the anticancer properties of Spirulina (SP) extract and understand its molecular mechanisms. The results showed that the administration of 1 g/kg of SP increased the antioxidant activity by raising levels of catalase (CAT) and superoxide dismutase (SOD), while decreasing the levels of malonaldehyde (MDA) and protein carbonyl. A histological examination revealed reduced tumor occurrence, decreased estrogen receptor expression, suppressed cell proliferation, and promoted apoptosis in SP protected animals. In addition, SP disrupted the G2/M phase of the MCF-7 cell cycle, inducing apoptosis and reactive oxygen species (ROS) accumulation. It also enhanced intrinsic apoptosis in MCF-7 cells by upregulating cytochrome c, Bax, caspase-8, caspase-9, and caspase-7 proteins, while downregulating Bcl-2 production. The main compounds identified in the LC-MS/MS study of SP were 7-hydroxycoumarin derivatives of cinnamic acid, hinokinin, valeric acid, and α-linolenic acid. These substances specifically targeted three important proteins: ERK1/2 MAPK, PI3K-protein kinase B (AKT), and the epidermal growth factor receptor (EGFR). Network analysis and molecular docking indicated a significant binding affinity between SP and these proteins. This was verified by Western blot analysis that revealed decreased protein levels of p-EGFR, p-ERK1/2, and p-AKT following SP administration. SP was finally reported to suppress MCF-7 cell growth and induce apoptosis by modulating the PI3K/AKT/EGFR and MAPK signaling pathways suggesting EGFR as a potential target of SP in breast cancer (BC) treatment.

Peucedanum decursivum (Miq.) Maxim (P. decursivum) is a traditional Chinese medicinal plant with pharmacological effects such as anti-inflammatory and anti-tumor effects, the root of which is widely used as medicine. Determining the spatial distribution and pharmacological mechanisms of metabolites is necessary when studying the effective substances of medicinal plants. As a means of obtaining spatial distribution information of metabolites, mass spectrometry imaging has high sensitivity and allows for molecule visualization. In this study, matrix-assisted laser desorption mass spectrometry (MALDI-TOF-MSI) and network pharmacology were used for the first time to visually study the spatial distribution and anti-inflammatory mechanism of coumarins, which are metabolites of P. decursivum, to determine their tissue localization and mechanism of action. A total of 27 coumarins were identified by MALDI-TOF-MSI, which mainly concentrated in the cortex, periderm, and phloem of the root of P. decursivum. Network pharmacology studies have identified key targets for the anti-inflammatory effect of P. decursivum, such as TNF, PTGS2, and PRAKA. GO enrichment and KEGG pathway analyses indicated that coumarins in P. decursivum mainly participated in biological processes such as inflammatory response, positive regulation of protein kinase B signaling, chemical carcinogenesis receptor activation, pathways in cancer, and other biological pathways. The molecular docking results indicated that there was good binding between components and targets. This study provides a basis for understanding the spatial distribution and anti-inflammatory mechanism of coumarins in P. decursivum.

Clematis Florida (CF) is a folk medicinal herb in the southeast of China, which is traditionally used for treating osteoarticular diseases. However, the mechanism of its action remains unclear. The present study used network pharmacology and experimental validation to explore the mechanism of CF in the treatment of rheumatoid arthritis (RA). Liquid chromatography–mass spectrometry (LC-MS/MS) identified 50 main compounds of CF; then, their targets were obtained from TCMSP, ETCM, ITCM, and SwissTargetPrediction databases. RA disease-related targets were obtained from DisGeNET, OMIM, and GeneCards databases, and 99 overlapped targets were obtained using a Venn diagram. The protein–protein interaction network (PPI), the compound–target network (CT), and the compound–potential target genes–signaling pathways network (CPS) were constructed and analyzed. The results showed that the core compounds were screened as oleanolic acid, oleic acid, ferulic acid, caffeic acid, and syringic acid. The core therapeutic targets were predicted via network pharmacology analysis as PTGS2 (COX-2), MAPK1, NF-κB1, TNF, and RELA, which belong to the MAPK signaling pathway and NF-κB signaling pathway. The animal experiments indicated that topical application of CF showed significant anti-inflammatory activity in a mouse model of xylene-induced ear edema and had strong analgesic effect on acetic acid-induced writhing. Furthermore, in the rat model of adjuvant arthritis (AA), topical administration of CF was able to alleviate toe swelling and ameliorate joint damage. The elevated serum content levels of IL-6, COX-2, TNF-α, IL-1β, and RF caused by adjuvant arthritis were reduced by CF treatment. Western blotting tests showed that CF may regulate the ERK and NF-κB pathway. The results provide a new perspective for the topical application of CF for treatment of RA.

Androgenetic alopecia (AGA) is the most prevalent hair loss disorder worldwide, driven by excessive sensitivity or response to androgen. Herbal extracts, such as Curcuma aeruginosa Roxb., have shown promise in AGA treatment due to their anti-androgenic activities and hair growth effects. However, the precise mechanism of action remains unclear. Hence, this study aims to elucidate the active compounds, putative targets, and underlying mechanisms of C. aeruginosa for the therapy of AGA using network pharmacology and molecular docking. This study identified 66 bioactive compounds from C. aeruginosa, targeting 59 proteins associated with AGA. Eight hub genes were identified from the protein–protein interaction network, namely, CASP3, AKT1, AR, IL6, PPARG, STAT3, HIF1A, and MAPK3. Topological analysis of components–targets network revealed trans-verbenol, myrtenal, carvone, alpha-atlantone, and isoaromandendrene epoxide as the core components with potential significance in AGA treatment. The molecular docking verified the binding affinity between the hub genes and core compounds. Moreover, the enrichment analyses showed that C. aeruginosa is involved in hormone response and participates in HIF-1 and MAPK pathways to treat AGA. Overall, this study contributes to understanding the potential anti-AGA mechanism of C. aeruginosa by highlighting its multi-component interactions with several targets involved in AGA pathogenesis.

Alzheimer’s disease (AD) is a neurodegenerative disorder that is projected by the WHO to affect over 100 million people by 2050. Clinically, AD patients undergoing long-term antipsychotic treatment often experience severe anxiety or depression in later stages. Furthermore, early-stage AD manifests with weakened α waves in the brain, progressing to diminished α and β waves in late-stage disease, reflecting changes in emotional states and disease progression. In this study, EEG signal analysis revealed that inhalation of Dalbergia pinnata (Lour.) Prain essential oil (DPEO) enhanced δ, θ, α and β wave powers in the frontal and parietal lobes, with a rising trend in the β/α ratio in the temporal lobe. These findings suggest an alleviation of anxiety and an enhancement of cognitive functions. Treatment of the AD SH-SY5Y (human neuroblastoma cells) cell model with DPEO resulted in decreased intracellular levels of Aβ, GSK-3β, P-Tau, IL-1β, TNF-α, IL-6, COX-2, OFR, and HFR, alongside reduced AchE and BchE activities and increased SOD activity. Network pharmacology analysis indicated a potential pharmacological mechanism involving the JAK-STAT pathway. Our study provides evidence supporting DPEO’s role in modulating anxiety and slowing AD pathological progression.

Tagetes erecta Linn. (TE) is traditionally used to treat cardiovascular, renal, and gastrointestinal diseases. In this study, we investigated the active compounds and targets of TE extract that may exert antiviral effects against influenza A. Active compounds and targets of TE extract were identified using the Traditional Chinese Medicine Systems Pharmacology database (TCSMP). The influenza A-related gene set was screened using GeneCards and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein–protein interaction (PPI) network was built to establish the hub targets. Pathway and target studies were conducted using Gene Expression Omnibus (GEO). The interactions between active compounds and potential targets were assessed by molecular docking. An in vitro study was performed using antiviral and plaque reduction assays. From the compound and target search, we identified 6 active compounds and 95 potential targets. We retrieved 887 influenza-associated target genes and determined 14 intersecting core targets between TE and influenza. After constructing a compound–target network, we discovered lutein and beta-carotene to be the key compounds. Next, PPI network analysis identified the top three hub genes associated with influenza (IL-6, HIF1A, and IL-1β). Similarly, GEO analysis revealed IL-6, TGFB1, and CXCL8 to be the top three target genes. In our docking study, we identified that lutein and IL-6 had the strongest bindings. Our in vitro experimental results revealed that the TE extract exhibited therapeutic rather than prophylactic effects on influenza disease. We identified lutein as a main active compound in TE extract, and IL-6 as an important target associated with influenza, by using data mining and bioinformatics. Our in vitro findings indicated that TE extract exerted protective properties against the influenza A virus. We speculated that lutein, as a key active component in TE extract, is largely responsible for its antiviral effects. Therefore, we suggest TE extract as an alternative in the treatment of influenza.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and poor prognosis. Meanwhile, doxorubicin, a chemotherapeutic agent for triple-negative breast cancer, has poor sensitivity. The objective of this study was to examine the effect of cordycepin on doxorubicin sensitivity and efficacy in the TNBC xenograft model and explore the relevant molecular pathways. The combination of the drugs in nude mice carrying MDA-MB-231 xenografts significantly reduced the volume, size, and weight of xenografts and improved the tumor inhibition rate. The drug combination was significantly more effective than cordycepin or doxorubicin alone, reflecting the fact that cordycepin enhanced the anti-tumor effects of doxorubicin in MDA-MB-231 xenografts. At the same time, the monitoring of several biological parameters failed to detect any obvious side effects associated with this treatment. After predicting the importance of the TNF pathway in inhibiting tumor growth using network pharmacology methods, we verified the expression of TNF pathway targets via immunohistochemistry and quantitative PCR. Furthermore, a TNF-α inhibitor was able to abrogate the beneficial effects of cordycepin and doxorubicin treatment in MDA-MB-231 cells. This clearly indicates the role of TNF-α, or related molecules, in mediating the therapeutic benefits of the combined treatment in animals carrying TNBC xenografts. The observations reported here may present a new direction for the clinical treatment of TNBC.

Paeonia lactiflora Pall. (PLP) is thought to promote blood circulation and remove blood stasis. This study used blood component analysis, network pharmacology, and molecular docking to predict the mechanism of PLP in the treatment of blood stasis syndrome (BSS). PLP was processed into Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). PRA and PRR could significantly reduce whole blood viscosity (WBV) at 1/s shear rates and could increase the erythrocyte aggregation index (EAI), plasma viscosity (PV), and erythrocyte sedimentation rate (ESR) of rats with acute blood stasis. They prolonged the prothrombin time (PT), and PRR prolonged the activated partial thromboplastin time (APTT). PRA and PRR increased the thrombin time (TT) and decreased the fibrinogen (FBG) content. All the results were significant (p < 0.05). Ten components of Paeoniflorin, Albiflorin, Paeonin C, and others were identified in the plasma of rats using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A protein–protein interaction network (PPI) analysis showed that AKT1, EGFR, SRC, MAPK14, NOS3, and KDR were key targets of PLP in the treatment of BSS, and the molecular docking results further verified this. This study indicated that PLP improves BSS in multiple ways and that the potential pharmacological mechanisms may be related to angiogenesis, vasoconstriction and relaxation, coagulation, and the migration and proliferation of vascular cells.

Ulcerative colitis (UC) is an inflammatory bowel disease that causes chronic inflammation in the large intestine. The etiology of UC is complex and incompletely understood, with potential contributing factors including genetic susceptibility, environmental influences, immune dysregulation, and gut barrier dysfunction. Despite available therapeutic drugs, the suboptimal cure rate for UC emphasizes the necessity of developing novel therapeutics. Traditional Chinese Medicine (TCM) has attracted great interest in the treatment of such chronic inflammatory diseases due to its advantages, such as multi-targets and low side effects. In this study, a mouse model of Dextran Sulfate Sodium (DSS)-induced acute colitis was established and the efficacy of Zhenqi Granule, a TCM preparation composed of the extractives from Astragali Radix and Fructus Ligustri Lucidi, was evaluated. The results showed that treatment with Zhenqi Granule prior to or post-DSS induction could alleviate the symptoms of colitis, including weight loss, diarrhea, hematochezia, colon length shortening, and pathological damage of colon tissues of the DSS-treated mice. Further, network pharmacology analysis showed that there were 98 common targets between the active components of Zhenqi Granule and the targets of UC, and the common targets were involved in the regulation of inflammatory signaling pathways. Our results showed that Zhenqi Granule had preventive and therapeutic effects on acute colitis in mice, and the mechanism may be that the active components of Zhenqi Granule participated in the regulation of inflammatory response. This study provided data reference for further exploring the mechanism of Zhenqi Granule and also provided potential treatment strategies for UC.