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Purpose: To characterize the active components and molecular mechanisms of action of Xiaoyin Granule (XYG), and also to determine its synergistic effect with acitretin on psoriasis. Methods: Bioactive targets of XYG, acitretin targets, and psoriasis-related targets were retrieved from public databases. Key bioactive compounds and targets were identified by bioinformatic and network pharmacology analysis. The binding affinities between bioactive compounds and crucial targets were evaluated through molecular docking analysis. Results: A comprehensive screening of XYG revealed the identification of 323 bioactive compounds and 324 corresponding targets. A total of 47 acitretin targets and 1706 psoriasis-related targets were identified. Venn plot identified 155 candidate targets that contributed to the synergistic effects of XYG and acitretin against psoriasis. Bioinformatics analysis demonstrated that the candidate targets were associated with diverse pathways that participate in signaling transduction. A clustering analysis of protein-protein interaction (PPI) revealed the presence of three distinct clusters, with cluster 3 exhibiting a significant association with immunity and potentially serving a crucial function in the therapeutic mechanisms of XYG and acitretin capsule in the treatment of psoriasis. A herb-compound-target-pathway network was constructed and revealed a variety of bioactive compounds, including quercetin, apigenin, and luteolin, and targets, viz, PTGS2, PRKACA, and MAPK14. Molecular docking demonstrated that the key bioactive compounds had favorable binding affinities with hub targets. Conclusion: This study provides insights into the potential mechanisms underlying the therapeutic effects of XYG when combined with acitretin capsules for treatment of psoriasis, thus laying a solid foundation for further investigations into its mechanism and clinical applications.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs, deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, the mixture of three herbs had a combinational effect. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFA-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

Wogonin is one of the main active components of Scutellaria baicalensis, which has anti-inflammatory, anti-angiogenesis, and anti-fibrosis effects. Nevertheless, the effect of wogonin on pulmonary hypertension (PH) still lacks systematic research. This study aims to elucidate the potential mechanism of wogonin against PH through network pharmacology and further verify it through biological experiments in pulmonary arterial smooth muscle cells (PASMCs). The potential targets and pathways of wogonin against PH were predicted and analyzed by network pharmacology methods and molecular docking technology. Subsequently, the proliferation of PASMCs was induced by platelet-derived growth factor-BB (PDGF-BB). Cell viability and migration ability were examined. The method of Western blot was adopted to analyze the changes in related signaling pathways. Forty potential targets related to the effect of wogonin against PH were obtained. Based on the protein–protein interaction (PPI) network, gene-ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment, and molecular docking, it was shown that the effect of wogonin against PH is closely related to the proliferation of PASMCs and the hypoxia-inducible factor-1α (HIF-1α) pathway. A variety of results from biological experiments verified that wogonin can effectively inhibit the proliferation, migration, and phenotypic transformation of PDGF-BB-mediated PASMCs. In addition, the anti-proliferation effect of wogonin may be achieved by regulating HIF-1/ NADPH oxidase 4 (NOX4) pathway.

Quercetin, a flavonoid with anti-inflammatory and anticancer properties, is expected to be an innovative anticancer therapeutic agent for papillary thyroid carcinoma (PTC). However, the downstream signaling pathways that mediate quercetin-dependent anticancer properties remain to be deciphered. Herein, potential targets of quercetin were screened with several bioinformatic avenues including PharmMapper, Gene Expression Omnibus (GEO) database, protein–protein interaction (PPI) network, and molecular docking. Besides, western blot, CCK-8 transwell analysis of migration and invasion, flow cytometric analysis, and colony formation assays were performed to investigate the underlying mechanism. We found four core nodes (MMP9, JUN, SPP1, and HMOX1) by constructing a PPI network with 23 common targets. Through functional enrichment analysis, we confirmed that the above four target genes are enriched in the TNF, PI3K-AKT, and NF-κB signaling pathways, which are involved in the inflammatory microenvironment and inhibit the development and progression of tumors. Furthermore, molecular docking results demonstrated that quercetin shows strong binding efficiency with the proteins encoded by these 4 key proteins. Finally, quercetin displayed strong antitumor efficacy in PTC cell lines. In this research, we demonstrated the application of network pharmacology in evaluating the mechanisms of action and molecular targets of quercetin, which regulates a variety of proteins and signaling pathways in PTC. These data might explain the mechanism underlying the anticancer effects of quercetin in PTC.

Liu Tang,1 Jiefang Gao,2 Xiaolei Li,2 Xiaoqin Cao,3 Benhong Zhou1 1Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2School of Pharmaceutical Sciences, Wuhan University, Wuhan, People’s Republic of China; 3School of Medicine, Jianghan University, Wuhan, People’s Republic of ChinaCorrespondence: Liu Tang; Benhong Zhou, Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China, Email tangliu900402@whu.edu.cn; benhongzh@whu.edu.cnPurpose: To undercover the underlying mechanisms of luteolin against atopic dermatitis (AD), clinically characterized by recurrent eczematous lesions and intense itching, based on network pharmacology, molecular docking and in vivo experimental validation.Methods: TCMSP, STITCH and SwissTargetPrediction databases were utilized to screen the corresponding targets of luteolin. Targets related to AD were collected from DisGeNET, GeneCards and TTD databases. PPI network of intersection targets was constructed through STRING 11.0 database and Cytoscape 3.9.0 software. GO and KEGG enrichment analysis were performed to investigate the critical pathways of luteolin against AD. Further, the therapeutic effects and candidate targets/signaling pathways predicted from network pharmacology analysis were experimentally validated in a mouse model of AD induced by 2, 4-dinitrofluorobenzene (DNFB).Results: A total of 31 intersection targets were obtained by matching 151 targets of luteolin with 553 targets of AD. Among all, 20 core targets were identified by PPI network topology analysis, including IL-6, TNF, IL-10, VEGFA, IL-4, etc., and molecular docking indicated that luteolin binds strongly to these core targets. KEGG pathway enrichment analysis suggested that the intersected targets were significantly enriched in IL-17 signaling pathway, Th17 cell differentiation, Th1 and Th2 cell differentiation, JAK/STAT signaling pathway, etc. The in vivo experiment validated that luteolin could alleviate AD-like skin symptoms, as evidenced by the lower SCORAD score, the reduced infiltration of mast cells and the recovery of skin barrier function. Furthermore, luteolin restored immune balance by regulating the production of Th1/Th2/Th17-mediated cytokines, which were both the predicted core targets. Moreover, luteolin inhibited the phosphorylation of JAK2 and STAT3 in the lesional skin.Conclusion: Together, the present study systematically clarifies the ameliorative effects and possible molecular mechanisms of luteolin against AD through the combination of network pharmacology and experimental validation, shedding light on the future development and clinical application of luteolin.Keywords: atopic dermatitis, luteolin, network pharmacology, target prediction, experimental validation

Background. Chronic obstructive pulmonary disease (COPD) is becoming a major public health burden worldwide. It is urgent to explore more effective and safer treatment strategy for COPD. Notably, Xuefu Zhuyu Decoction (XFZYD) is widely used to treat respiratory system diseases, including COPD, in China. Objective. This study is aimed at comprehensively evaluating the therapeutic effects and molecular mechanism of XFZYD on COPD. Methods. Original clinical studies were searched from eight literature databases. Meta-analysis was conducted using the Review Manager software (version 5.4.1). Network pharmacology and molecular docking experiments were utilized to explore the mechanisms of action of XFZYD. Results. XFZYD significantly enhanced the efficacy of clinical treatment and improved the pulmonary function and hypoventilation of COPD patients. In addition, XFZYD significantly improved the hypercoagulability of COPD patients. The subgroup analysis suggested that XFZYD exhibited therapeutic effects on both stable and acute exacerbation of COPD. XFZYD exerted its therapeutic effects on COPD through multicomponent, multitarget, and multipathway characteristics. The intervention of the PI3K-AKT pathway may be the critical mechanism. Conclusion. The application of XFZYD based on symptomatic relief and supportive treatment is a promising clinical decision. More preclinical and clinical studies are still needed to evaluate the safety and therapeutic effects of long-term use of XFZYD on COPD.

Background. With the aging of the social population, Osteoarthritis (OA) has already become a vital health and economic problem globally. Shujin Dingtong recipe (SJDTR) is an effective formula to treat OA in China. Although studies have shown that SJDTR can significantly alleviate OA symptoms, its mechanism still remains unclear. Purpose. This study is aimed at investigating the potential mechanism of SJDTR for the treatment of OA based on network pharmacology and molecular docking. Methods. Main ingredients of SJDTR were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. OA disease targets were obtained from the Gene Expression Omnibus (GEO) database. The overlapped targets and signaling pathways were explored using Protein-Protein Interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Following this, the core targets were employed to dock with corresponding components via molecular docking in order to further explore the mechanism of SJDTR in the treatment of OA. Results. From network pharmacology, we found 100 active components of SJDTR, 31 drug and OA-related targets, 1161 GO items, and 91 signaling pathways. Based on the analysis with PPI network and molecular docking, TP53, CCNB1, and MMP-2 were selected for the core targets of SJDTR against OA. Molecular docking demonstrated that Quercetin, Baicalein, and Luteolin, had good binding with the TP53, CCNB1, and MMP-2 protein, respectively. Conclusion. To conclude, our study suggested the main ingredients of SJDTR might alleviate the progression of OA through multiple targets and pathways. Additionally, network pharmacology and molecular docking, as new approaches, were adopted for systematically exploring the potential mechanism of SJDTR for the treatment of OA.

Objective. This study systematically explored the mechanism of Rhizoma Coptidis-Eupatorium fortunei in treating type 2 diabetes mellitus (T2DM) by using network pharmacology and molecular docking methods. Methods. The TCMSP database was used to screen out the active ingredients and related targets of Rhizoma Coptidis-Eupatorium fortunei (R-E) drug pair. GeneCards, OMIM, DrugBank, and other databases were used to screen the related targets of T2DM, and then, the UniProt database was used to standardize the relevant targets of T2DM. Then, the Venn analysis was performed on the active ingredient-related targets and disease-related targets of R-E drugs to find the intersection targets. Using the STRING database and Cytoscape software, the PPI network and “drug-active ingredient-target-disease” network are constructed by intersecting targets and corresponding active ingredients. Through the cluster profiler package in the R software, GO function enrichment analysis and KEGG pathway enrichment analysis were carried out on the intersection targets and the screened core targets, and the prediction results were verified by molecular docking. Results. Taking OB ≥ 30 % and DL ≥ 0.18 as the standard, a total of 25 effective active ingredients of R-E drug pairs were screened, including berberine, palmatine, coptisine, and so on. After corresponding, 19 effective chemical components and 284 targets of the R-E drug pair were obtained. After searching multiple disease databases, 1289 T2DM-related targets were screened. After the summary, 159 common targets were obtained in this study. Finally, in the bioinformatics analysis, this study concluded that quercetin, luteolin, berberine, palmatine, and coptisine are the main chemical components of the R-E drug pair. ESR1, MAPK1, AKT1, TP53, IL6, and JUN are the important core targets. GO and KEGG enrichment analyses showed that Rhizoma Coptidis-Eupatorium fortunei could improve T2DM by regulating multiple biological processes and pathways. Molecular docking results showed that berberine, palmatine, and coptisine had higher binding to the core target, and MAPK1, AKT1, and IL6 could stably bind to the active ingredients of Rhizoma Coptidis-Eupatorium fortunei. Conclusion. Rhizoma Coptidis-Eupatorium fortunei may have therapeutic effects on T2DM such as anti-inflammatory and regulating glucose and lipid metabolism through multiple components, multiple targets, and multiple signaling pathways, which provides a scientific basis for further research on the hypoglycemic effect of Rhizoma Coptidis-Eupatorium fortunei drug pair.

Purpose. To explore the active compounds of the Chinese medicine prescriptions of Bushen Hugu Decoction (BHD) and demonstrate its mechanisms against malignant tumor bone metastasis (BM) through network pharmacology and molecular docking analysis.Methods. The main components and targets of BHD were retrieved from the TCMSP database, and the targets were normalized by UniProt. The Herbs-Components-Targets network of BHD was established by Cytoscape. The main BM targets were obtained from GeneCards, TTD, DrugBank, and OMIM. STRING and Cytoscape were used to construct a PPI network and obtain hub genes. DAVID and Metascape were used for GO and KEGG enrichment analyses. According to the network topology parameters, the top 4 components were selected for molecular docking verification with the core targets. Results. Compound–target network of BHD mainly contained 51 compounds and 259 corresponding targets including 107 BHD-BM targets. PPI interaction network and subnetworks identified ten hub genes. GO enrichment analysis found 1970 terms ( p < 0.05 ), and 164 signaling pathways ( p < 0.05 ) were found in KEGG, including PI3K-Akt signaling pathway, proteoglycans in cancer, prostate cancer, MAPK signaling pathway, and IL-17 signaling pathway. Molecular docking analysis showed that the active components of BHD, quercetin, luteolin, kaempferol, and aureusidin have good binding activity to the core targets. Conclusion. The potential molecular target and signaling pathways were found for BHD major active components. It provides guidance for the future mechanism research of the BHD in malignant tumor bone metastasis. This study also established the foundation for the new strategy for the pharmacology study of Chinese medicine.

Objective. This study is aimed at screening out effective active compounds of Qizhen capsule (QZC) and exploring the underlying mechanisms against gastric cancer (GACA) by combining both bioinformatic analysis and experimental approaches. Weighted gene coexpression network analysis (WGCNA), network pharmacology, molecular docking simulation, survival analysis, and data-based differential gene and protein expression analysis were employed to predict QZC’s potential targets and explore the underlying mechanisms. Subsequently, multiple experiments, including cell viability, apoptosis, and protein expression analyses, were conducted to validate the bioinformatics-predicted therapeutic targets. The results indicated that luteolin, rutin, quercetin, and kaempferol were vital active compounds, and TP53, MAPK1, and AKT1 were key targets. Molecular docking simulation showed that the four abovementioned active compounds had high binding affinities to the three main targets. Enrichment analysis showed that vital active compounds exerted therapeutic effects on GACA through regulating the TP53 pathway, MAPK pathway, and PI3K/AKT pathway. Furthermore, data-based gene expression analysis revealed that TP53 and JUN genes were not only differentially expressed between normal and GACA tissues but also correlated with clinical stages. In parallel, in vitro experimental results suggested that QZC exerted therapeutic effects on GACA by decreasing IC50 values, downregulating AKT expression, upregulating TP53 and MAPK expression, and increasing apoptosis of SGC-7901 cells. This study highlights the potential candidate biomarkers, therapeutic targets, and basic mechanisms of QZC in treating GACA, providing a foundation for new drug development, target mining, and related animal studies in GACA.

Due to the rapid development of bioinformatics, network pharmacology and molecular docking approaches have been successfully applied in the investigation of mechanisms of action. Here, we combined network pharmacology and molecular docking to predict the targets and reveal the molecular mechanism responsible for regulating autophagy by alliin. Based on the influence of alliin on autophagy, the targets of alliin were screened on the basis of different rules such as structural similarity by Pharmmapper, and genes associated with autophagy were collected from the GeneCards database. We focused on clarifying the biological processes and signalling pathways related to autophagy. Through the cytoHubba plug-in and a series of integrated bioinformatics analyses, the top nine hub nodes with higher degrees were obtained. And finally, through the LibDock included in Discovery Studio 2019, molecular docking method was adopted to declare the reliability of the interaction between alliin and hub targets. The results suggest that alliin-activated autophagy was possibly associated with pathways in cancer and the PI3K-AKT signalling pathway. Furthermore, the potential targets (AKT1, MAPK14, MAPK, HSPA8, EGFR, HSP90AA1, SRC HSPA1A and HSP90AB1) were swimmingly screened on the basis of this practical strategy. Molecular docking analysis indicates that alliin can bind with AKT1 and EGFR with good binding scores. This network pharmacology could be an invaluable strategy for the investigation of action mechanisms of alliin-activated autophagy. This study not only provides new and systematic insights into the underlying mechanism of alliin on autophagy, but also provides novel ideas for network approaches for autophagy-related research.

Acute myeloid leukaemia (AML) is a rapidly fatal blood cancer that is characterised by the accumulation of immature myeloid cells in the blood and bone marrow as a result of blocked differentiation. Methods which identify master transcriptional regulators of AML subtype-specific leukaemia cell states and their combinations could be critical for discovering novel differentiation-inducing therapies. In this proof-of-concept study, we demonstrate a novel utility of the Mogrify ® algorithm in identifying combinations of transcription factors (TFs) and drugs, which recapitulate granulocytic differentiation of the NB4 acute promyelocytic leukaemia (APL) cell line, using two different approaches. In the first approach, Connectivity Map (CMAP) analysis of these TFs and their target networks outperformed standard approaches, retrieving ATRA as the top hit. We identify dimaprit and mebendazole as a drug combination which induces myeloid differentiation. In the second approach, we show that genetic manipulation of specific Mogrify ®-identified TFs (MYC and IRF1) leads to co-operative induction of APL differentiation, as does pharmacological targeting of these TFs using currently available compounds. We also show that loss of IRF1 blunts ATRA-mediated differentiation, and that MYC represses IRF1 expression through recruitment of PML-RARα, the driver fusion oncoprotein in APL, to the IRF1 promoter. Finally, we demonstrate that these drug combinations can also induce differentiation of primary patient-derived APL cells, and highlight the potential of targeting MYC and IRF1 in high-risk APL. Thus, these results suggest that Mogrify ® could be used for drug discovery or repositioning in leukaemia differentiation therapy for other subtypes of leukaemia or cancers.

Background. Polydatin (PD) is the primary active compound in Polygonum cuspidatum Sieb and has been demonstrated to exert anti-inflammatory and neuroprotective activities. In the present study, we aimed to explore the therapeutic mechanisms of PD against chemotherapy-induced neuropathic pain. Methods. The putative targets of PD were obtained from the CTD and SwissTargetPrediction databases. Neuropathic pain- and VIN-related targets were collected from the CTD and GeneCards databases. Subsequently, the intersection targets were obtained using the Venn tool, and the protein-protein interaction (PPI) was constructed by the STRING database. GO and KEGG enrichment analyses were performed to investigate the biological functions of the intersection targets. Further, a rat model of VIN-induced neuropathic pain was established to confirm the reliability of the network pharmacology findings. Results. A total of 46 intersection targets were identified as potential therapeutic targets, mainly related to neuroinflammation. KEGG pathway analysis indicated that the IL-17 signaling pathway was involved in the mechanism of the antinociceptive effect of PD. PPI network analysis indicated that RELA, IL-6, TP53, MAPK3, and MAPK1 were located at crucial nodes in the network. Additionally, PD exerted an antinociceptive effect by increasing the nociceptive threshold. The results of qRT-PCR, western blot, and immunohisochemistry indicated that PD inhibited the IL-6, TP53, and MAPK1 levels in VIN-induced neuropathic pain rats. Conclusions. Overall, this research provided evidence that suppressing inflammatory signaling pathways might be a potential mechanism action of PD’s antinociceptive effect against VIN-induced neuropathic pain.

Chronic liver disease(CLD) is a slow-developing and long-term disease that can cause serious damage to the liver. Thus far, it has been associated with viral hepatitis, non-alcoholic fatty liver disease(NAFLD), alcoholic liver disease(ALD), hepatic fibrosis(HF), liver cirrhosis (LC), and liver cancer. Qinghao Biejia Decoction (QBD) is a classic ancient Chinese herbal prescription with strong immune-enhancing, anti-inflammatory, and anti-tumor effects. In this study, we used a network pharmacology approach to investigate the molecular mechanisms of QBD in the inflammation-carcinoma transformation process of chronic liver disease. Two key drug targets, MAPK1 and PIK3CA, were screened using network pharmacology and molecular docking techniques, revealing dihydroartemisinin, artesunate, 12-O-Nicotinoylisolineolone, caffeic acid, and diincarvilone A as active ingredients involved in QBD mechanisms. The main signaling pathways involved were the PI3K-AKT signaling pathway and MAPK signaling pathway. In summary, our results indicated that QBD affects the inflammatory transformation of chronic liver disease through MAPK1 and PIK3CA and signaling pathways MAPK and PI3K/AKT. These data provide research direction for investigating the mechanisms underlying the inflammation-carcinoma transformation process in QBD for chronic liver disease.

Purpose. Based on the method of network pharmacology to explore the mechanism of the cervical prescription (CP) in the treatment of cervical cancer (CC). Methods. We obtained the active ingredients and potential targets in the CP from the literature and the systematic pharmacological analysis platform of traditional Chinese medicine (BATMAN-TCM); the database was used to search for targets related to cervical cancer and to map CP and targets; the core targets were screened, and the protein-protein interaction network (PPI) was constructed using the TCM compound-target network and STRING database. Gene ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) pathway enrichment analysis of overlapping targets were performed using DAVID 6.8 online tool. Results. The CP contains 2 active ingredients, corresponding to 301 nonreactive targets; 10 GO biological process related items and 73 signal pathways were obtained. Cell experiments confirmed that the medicated serum of CP could effectively inhibit the proliferation and invasion ability of Hela cells. Conclusion. This study provides valuable information for TCM researchers and clinicians to better understand the main therapeutic targets and therapeutic roles of herbal decoctions in clinical settings. The results of our study preliminarily clarified that the cervical prescription has an inhibitory effect on cervical cancer cells.

The main pathophysiological abnormalities in type 2 diabetes (T2D) include pancreatic β-cell dysfunction and insulin resistance. Due to hyperglycemia, patients receive long-term treatment. However, side effects and drug tolerance usually lead to treatment failure. GuaLouQuMaiWan (GLQMW), a common traditional Chinese medicine (TCM) prescription, has positive effects on controlling blood sugar and improving quality of life, but the mechanism is still unclear. To decipher their molecular mechanisms, we used a novel computational systems pharmacology-based approach consisting of bioinformatics analysis, network pharmacology, and drug similarity comparison. We divided the participants into nondisease (ND), impaired glucose tolerance (IGT), and type 2 diabetes groups according to the WHO’s recommendations for diabetes. By analyzing the gene expression profile of the ND-IGT-T2D (ND to IGT to T2D) process, we found that the function of downregulated genes in the whole process was mainly related to insulin secretion, while the upregulated genes were related to inflammation. Furthermore, other genes in the ND-IGT (ND to IGT) process are mainly related to inflammation and lipid metabolic disorders. We speculate that 17 genes with a consistent trend may play a key role in the process of ND-IGT-T2D. We further performed target prediction for 50 compounds in GLQMW that met the screening criteria and intersected the differentially expressed genes of the T2D process with the compounds of GLQMW; a total of 18 proteins proved potential targets for GLQMW. Among these, RBP4 is considerably related to insulin resistance. GO/KEGG enrichment analyses of the target genes of GLQMW showed enrichment in inflammation- and T2D therapy-related pathways. Based on the RDKit tool and the DrugBank database, we speculate that (-)-taxifolin, dialoside A_qt, spinasterol, isofucosterol, and 11,14-eicosadienoic acid can be used as potential drugs for T2D via molecular docking and drug similarity comparison.

Background and Objective: Inflammation is a common disease which can induce many diseases. There are unique advantages of Traditional Chinese Medicine (TCM) to anti-inflammation. Tieguanyin (TGY) is a well-known beverage; the quality is determined by aroma, taste, liquor color, and shape. The volatile compounds produce the flavor of tea, which can be lost with the increase of storage time. TGY has an excellent antiinflammatory effect; its volatile compounds also have an anti-inflammatory impact that is unclear. This study aimed to identify volatile compounds and anti-inflammatory mechanisms within the validity period (TGY1) and the out-of-date (TGY2). Methods: The volatile compounds of TGY1 and TGY2 were analyzed with headspace solid-phase microextraction (HS-PME) and identified by Gas chromatography-mass spectrometry (GC-MS). The percentage of volatile compounds was calculated by the peak area normalization method. The compounds of the targets were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP), PubChem Database, and Swiss Target Prediction database. Next, the disease potential targets were screened by the GeneCards database, Online Mendelian Inheritance in Man (OMM) database, and Therapeutic Target Database (TTD). Furthermore, core targets were screened by the Search Tool for the Retrieval of Inter-acting Genes/Proteins (STRING) database. Then, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of core targets was performed by the ClueGo plugin Cytoscape 3.7.1 software. At last, Autodock vina software performed molecular docking between the main compounds and core targets. Results: Significant differences in volatile compounds and percentage contents in TGY were observed; the 61 volatile compounds in TGY1 and 57 volatile compounds in TGY2 were identified. After excluding the unidentified compounds, a total of 47 volatile compounds were obtained from TGY1 and TGY2. With the use of network pharmacology, 34 core targets and 23 signaling pathways from TGY1, 28 core targets, and 19 signaling pathways from TGY2 were screened. The main common core targets of TGY1 and TGY2 contained MAPK3, TNF, MAPK1, SRC, etc., while the main different core targets included PTGS2, CAT, etc. A total of 12 biological processes are shared by TGY1 and TGY2, among which the cellular response to oxidative stress is the primary biological process. The different biological processes of TGY1 and TGY2 include cellular response to lipopolysaccharide, androgen receptor signaling pathway, etc. There were 14 common signaling pathways in TGY1 and TGY2, among which the thyroid hormone signaling pathway is the main common signaling pathway. The differential signaling pathways in TGY1 and TGY2 included the erbB signaling pathway, Chagas disease, etc. Molecular docking results showed that the ordinand and differential volatile compounds of TGY1 and TGY2 had different binding forces with the core targets. Conclusion: The GC-MS experiment showed significant differences in volatile compounds and percentage contents in TGY1 and TGY2. Network pharmacology indicated that they have anti-inflammatory effects. Besides, they were different in core targets, biological processes, and signaling pathways but shared similar anti-inflammatory mechanisms. Molecular docking results showed that the binding force of the TGY1 compounds to the core target is greater than that of the TGY2. Therefore, expired TGY affects volatile compounds, resulting in differences in the anti-inflammatory mechanism. The study provided a theoretical framework for further development and application of used medicinal and edible species. In addition, the application of expired TGY under safe conditions can also have anti-inflammatory effects. These results shed new light on the rational use of resources.

Total glucosides of peony (TGP) is extracted from Paeonia lactiflora Pallas, which has been approved for rheumatoid arthritis (RA) treatment. There were approximately 15 monoterpene glycosides identified in TGP. Pervious researches focused on the effects of TGP and the major ingredient paeoniflorin (PF), but the functions of other monoterpene glycosides and their interactions were not clear. Network pharmacology has been one of the new strategies for multi-target drug discovery. In this study, we investigate the functions of all components of TGP and their interactions in RA treatment based on network pharmacology methods.The components of TGP were searched out the Web of Science, PubMed, China National Knowledge Infrastructure databases; then we identified the potential targets based of chemical similarity in the Similarity Ensemble Approach. The molecular related with RA were obtained from DrugBank, GeneCards, DisGeNET and Online Mendelian Inheritance in Man (OMIM) databases. The components-targets-disease network was constructed and analyzed with Cytoscape software; Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted with R for function analysis. The hub components-targets interactions were validated with Autodock Vina.Twenty potential targets of TGP were predicted for RA treatment. The major components of TGP, PF and albiflorin (AF) had more predicted targets. Hub targets of TGP were LGALS3/9, VEGFA, FGF1, FGF2, IL-6, IL-2, SELP, PRKCA and ERAP1. These targets ameliorated RA mainly through inhibiting leukocyte recruitment and angiogenesis. Enriched pathways including VEGFR pathway, signaling by interleukins, PI3K-Akt signaling pathway, platelet activation, extracellular matrix organization, and so on. The combination of PF, AF and lactiflorin (LF) with the hub targets was further validated using docking program.We investigated the comprehensive mechanism of TGP for RA treatment. We analyzed the different targets of the components in TGP and predicted the new effects of TGP on inhibiting leukocyte recruitment and angiogenesis. This study provides a better understanding of TGP on the RA treatment.

Jin Wu,1 Yiting Luo,1 Yan Shen,2 Yuyao Hu,2 Fangyuan Zhu,1 Jiaqian Wu,1 Yingchao Liu3 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, People’s Republic of China; 3Academic Affairs Office, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Yingchao Liu, Academic Affairs Office, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China, Email jcjsylyc@163.comBackground: Traditional Chinese medicine (TCM) has the advantage of multi-component and multi-target, which becomes a hot spot in the treatment of numerous diseases. Shaoyao decoction (SYD) is a TCM prescription, which is mainly used to treat damp-heat dysentery clinically, with small side effects and low cost. However, its mechanism remains elusive. The purpose of this study is to explore the mechanism of SYD in the treatment of mice with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) through metabolomics and network pharmacology, and verify through molecular docking and immunohistochemistry, so as to provide a scientific basis for the role of SYD in the treatment of UC.Materials and Methods: Firstly, DSS-induced UC models were established and then untargeted metabolomics analysis of feces, livers, serum and urine was performed to determine biomarkers and metabolic pathways closely related to the role of SYD. Besides, network pharmacology was applied to screen the active components and UC-related targets, which was verified by molecular docking. Finally, metabonomics and network pharmacology were combined to draw the metabolite-pathway-target network and verified by immunohistochemistry.Results: Metabolomics results showed that a total of 61 differential metabolites were discovered in SYD-treated UC with 3 main metabolic pathways containing glycerophospholipid metabolism, sphingolipid metabolism and biosynthesis of unsaturated fatty acids, as well as 8 core targets involving STAT3, IL1B, IL6, IL2, AKT1, IL4, ICAM1 and CCND1. Molecular docking demonstrated that the first five targets had strong affinity with quercetin, wogonin, kaempferol and baicalein. Combined with metabolomics and network pharmacology, sphingolipid signaling pathway, PI3K/AKT-mTOR signaling pathway and S1P3 pathway were identified as the main pathways.Conclusion: SYD can effectively ameliorate various symptoms and alleviate intestinal mucosal damage and metabolic disorder in DSS induced UC mice. Its effect is mainly related to sphingolipid metabolism, PI3K/AKT-mTOR signaling pathway and S1P3 pathway.Keywords: metabolomics, UPLC-Q-TOF-MS, network pharmacology, Shaoyao decoction, ulcerative colitis

Background: As COVID-19 pandemic continues to affect people’s lives, the government of India gave emergency use approval to the ayurvedic antimalarial drug Ayush-64 in April 2021 to treat asymptomatic COVID-19 positive and mild COVID-19 positive patients. Objective: This study aims to explore the therapeutic potential of Ayush-64 to treat COVID-19 and provide a new approach for repurposing Ayurvedic drugs. Methods: The bioactives present in Ayush-64 were found along with their targets, and a plantbioactive- target network was created. A protein-protein interaction network of the common targets of Ayush-64 and COVID-19 was constructed and analyzed to find the key targets of Ayush-64 associated with the disease. Gene ontology and pathway enrichment analysis were performed to find COVID-19 related biological processes and pathways involved by the key targets. The key bioactives were docked with SARS-CoV-2 main protease 3CL, native Human Angiotensin-converting Enzyme ACE2, Spike protein S1, and RNA-dependent RNA polymerase RdRp. Results: From the 336 targets for Ayush-64, we found 38 key targets. Functional enrichment analysis of the key targets resulted in 121 gene ontology terms and 38 pathways. When molecular docking was performed with four receptors, thirteen bioactives showed good binding affinity comparable to that of the eight drugs presently used to treat COVID-19. Conclusion: Network pharmacological analysis and molecular docking study of Ayush-64 revealed that it can be recommended to treat COVID-19. Further in vitro and in vivo studies are needed to confirm the results. The study demonstrated a new approach for repurposing Ayurvedic drugs.

Objective. Thin endometrium is considered as a leading cause of infertility, recurrent pregnancy loss, and repeated implantation failure. The seed of Cuscutae Semen (CS) has been used to prevent aging and improve sexual function in Traditional Chinese Medicine. However, the pharmacological mechanism of CS in preventing and treating thin endometrium remains to be elucidated. Methods. Three public databases, TCMSP, GeneCards, and OMIM, were searched to collect the main active compounds and putative molecules of CS, as well as the targets of thin endometrium, respectively. The CS and thin endometrium common targets were subject to protein-protein interaction (PPI) analysis followed by functional enrichment analysis. The best binding mode of CS compounds and common target proteins was evaluated by molecular docking and analysis in the AutoDockTools. Results. In total, 11 main active compounds, 102 drug target proteins, and 70 CS and thin endometrium common targets were identified. There were 68 nodes with 722 edges in the PPI network; HIF1A, MYC, ESR1, and EGFR were the top 4 targets. After functional enrichment analysis, it was revealed that the therapeutic effects of active compounds of CS on thin endometrium were achieved through cellular response to chemical stress, transcription regulator, DNA-binding transcription factor binding, chemical carcinogenesis-receptor activation, lipid, and atherosclerosis. The molecular docking analysis revealed that the 3 active compounds of CS, quercetin, matrine, and isorhamnetin, have good binding ability with their targets, HIF1A, MYC, ESR1, and EGFR. Conclusion. Our study uncovers the main active compounds in CS and their corresponding targets related to thin endometrium which explains the pharmacological mechanism underlying therapeutic effects of CS on thin endometrium.

Shen-Shi-Jiang-Zhuo formula (SSJZF) exhibits a definite curative effect in the clinical treatment of non-alcoholic fatty liver disease (NAFLD).To explore the therapeutic effect and mechanism of SSJZF on NAFLD.Sprague Dawley rats were randomly divided into control, NAFLD, positive drug (12 mg/kg/day), SSJZF high-dose (200 mg/kg/day), SSJZF middle-dose (100 mg/kg/day), and SSJZF low-dose (50 mg/kg/day) groups. After daily intragastric administration of NAFLD rats for 8 weeks, lipid metabolism and hepatic fibrosis were evaluated by biochemical indices and histopathology. Then we uncovered the main active compounds and mechanism of SSJZF against NAFLD by integrating RNA-sequencing and network pharmacology, and PI3K/AKT pathway activity was verified by western blot.High dose SSJZF had the best inhibitory effect on hepatic lipid accumulation and fibrosis in rats with NAFLD, which significantly down-regulatedWe found for first time that SSJZF improved NAFLD in rats by activating the PI3K/Akt pathway. These findings provide scientific support for SSJZF in the clinical treatment of NAFLD and contribute to the development of new NAFLD drugs.

Matrine and glycyrrhizin are representative active ingredients of traditional Chinese medicine (TCM) used in clinical practice. Studies have demonstrated that matrine has antitumor pharmacological effects and that glycyrrhizin protects liver function. However, the potential bioactive compounds and mechanisms remain unknown, as well as whether they have synergistic effects in killing cancer cells and protecting liver cells. To investigate the synergistic effects and mechanism of matrine combined with glycyrrhizin in hepatocellular carcinoma (HCC) treatment, we used both network pharmacology and bioinformatics analyses. First, the chemical gene interaction information of matrine and glycyrrhizin was obtained from the PubChem database. The pathogenic genes of HCC were accessed from five public databases. The RNA sequencing data and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA). Next, the overlapping genes among the potential targets of matrine and glycyrrhizin and HCC-related targets were determined using bioinformatics analysis. We constructed the drug-target interaction network. Prognosis-associated genes were acquired through the univariate Cox regression model and Lasso-Cox regression model. The results were verified by the International Cancer Genome Consortium (ICGC) database. Finally, we predicted the immune function of the samples. The drug-target interaction network consisted of 10 matrine and glycyrrhizin targets. We selected a Lasso-Cox regression model consisting of 3 differentially expressed genes (DEGs) to predict the efficacy of the combination in HCC. Subsequently, we successfully predicted the overall survival of HCC patients using the constructed prognostic model and investigated the correlation of the immune response. Matrine and glycyrrhizin have synergistic effects on HCC. The model we obtained consisted of three drug-target genes by Lasso-Cox regression analysis. The model independently predicted the combined effect of matrine and glycyrrhizin in HCC treatment and OS, which will be helpful for guiding clinical treatment. The prognostic model was correlated with the immune cells and immune checkpoints of patients, which had an adjuvant effect on HCC immunotherapy. Matrine and glycyrrhizin can have therapeutic effects on HCC by promoting the production or enhancing the core gene activity in the drug network and improving the immune system function of patients.

Amyloid β-protein (Aβ)-induced apoptosis and oxidative stress of human brain microvascular endothelial cells(BMECs) are contributors to the development of Alzheimer's disease (AD). Acteoside has shown its therapeutic potential for AD treatment. Therefore, this study investigated the effect of acteoside on Aβ-induced blood-brain barrier damage, oxidative stress and apoptosis as well as to explore the underlying mechanisms through network pharmacology.The study used Aβ to induce human BMECs to construct an in-vitro injury model. Following treatment with acteoside, transendothelial electrical resistance (TEER), RT-qPCR and Western blot were used to evaluate the permeability of BMECs. The apoptosis level was detected by TUNEL and Western blot, ROS assay kit was used for the detection of reactive oxygen species (ROS) expression. The let-7g-5p expression level was detected by RT-qPCR. After additional treatment with let-7g-5p inhibitor, corresponding assays were performed again. Finally, network pharmacology was used to verify the mechanism.Acteoside decreased the permeability, oxidative stress and cell apoptosis of Aβ-stimulated cells. More importantly, acteoside-activated let-7g-5p and additional treatment with let-7g-5p inhibitor abated the effects of acteoside on Aβ-induced permeability, oxidative stress and apoptosis of Aβ-stimulated BMECs. According to network pharmacology, 233 targeted genes of acteoside and 122 potential targets of let-7g-5p were determined by screening several databases, and two targets called Casp-3 and ITGB3 were obtained after taking the intersection.In conclusion, these results reveal that acteoside-activated let-7g-5p attenuating Aβ-induced increased permeability and apoptosis of human BMECs.

The characteristics of chemical components or groups of chemical components in traditional Chinese medicines (TCMs) determine their clinical efficacy. Quality markers (Q-markers) is of great significance for standardizing the quality control system of TCM.We aimed to develop a new strategy to discover potential Q-markers of TCM by integrating chemometrics, network pharmacology, and molecular docking, using Centipeda minima (also known as ebushicao [EBSC]) as an example.First, fingerprints of different batches of EBSC and its counterfeit Arenaria oreophila (also known as zaozhui [ZZ]) were established. Second, chemometric analysis was conducted to determine the influence of varying authenticity/batches of herbs on quality and the chemical markers were screened out. Third, network pharmacology and molecular docking simulations were used to verify the relationship between active ingredients and targets. Lastly, potential Q-markers were selected based on TCM theory.The chemical profiles of EBSC and ZZ were investigated. It was found that different batches of EBSC have differences in chemical composition. Based on our chemometric analysis, chlorogenic acid, rutin, isochlorogenic acid A, quercetin, arnicolide D, and brevilin A were selected as candidate active ingredients. ATIL6, EGFR, CASP3, MYC, HIF1A, and VEGFA were the main targets. Molecular docking was used to verify the binding ability. Based on the concept of Q-marker, arnicolide D and brevilin A were identified as potential Q-markers for EBSC.Our strategy could be used as a practical approach to discover Q-markers of TCM to evaluate overall chemical consistency.

Chronic atrophic gastritis (CAG) is a common chronically digestive disease which is notoriously characterized by atrophy of the epithelium and glands of the gastric mucosa, reduced number, thinning of the gastric mucosa, thickening of the mucosal base, or pyloric glandular hyperplasia and intestinal glandular hyperplasia, or with atypical hyperplasia. Banxia Xiexin decoction (BXD) has been applied for two thousand years and is considered an effective therapy for functional dyspepsia, gastroesophageal reflux disease and colon cancer. In this current study, to probe into the underlying mechanism of BXD on CAG, network pharmacology was conducted to collect druggable ingredients and predicted targets of BXD and the CAG-associated targets were harvested to take intersection with druggable ingredients from BXD predicted targets to obtain potential critical action targets. Subsequently, GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted to elucidate the underlying mechanisms and roles from the perspective of overall pathways and cellular functions. Eventually, molecular docking integrated with molecular dynamics simulations was conducted to further investigate the mechanism of action of BXD active ingredients on CAG from drug molecule-target interactions and to provide a theoretical basis for BXD drug development.

Background. Astragalus membranaceus (Huang-qi, AM) and Angelica sinensis (Dang-gui, AS) are common Chinese herbal medicines and have historically been used in spinal cord injury (SCI) therapies. However, the underlying molecular mechanisms of AM&AS remain little understood. The purpose of this research was to explore the bioactive components and the mechanisms of AM&AS in treating SCI according to network pharmacology and the molecular docking approach. Methods. AM&AS active ingredients were first searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicine Information Database (TCM-ID). Meanwhile, we collected relevant target genes of SCI through the GeneCards database, OMIM database, PharmGkb database, DurgBank database, and TDD database. By utilizing the STRING database, we constructed a network of protein-protein interactions (PPIs). In addition, we used R and STRING to perform GO and KEGG function enrichment analyses. Subsequently, AutoDock Vina was employed for a molecular docking study on the most active ingredients and most targeted molecules to validate the results of the network pharmacology analysis mentioned above. Result. The overall number of AM&AS active compounds identified was 22, while the number of SCI-related targets identified was 159. Then, the 4 key active ingredients were MOL000098 quercetin, MOL000422 kaempferol, MOL000354 isorhamnetin, and MOL000392 formononetin. A total of fourteen core targets were TP53, ESR1, MAPK1, MTC, HIF1A, HSP90AA1, FOS, MAPK14, STAT1, AKT1, EGFR, RELA, CCND1, and RB1. The KEGG enrichment analysis results indicated that lipid and atherosclerosis, PI3K-Akt signaling pathway, human cytomegalovirus infection, fluid shear stress, and atherosclerosis, etc., were enhanced with SCI development. Based on the analyses of docked molecules, four main active compounds had high affinity for the key targets. Conclusions. Altogether, it identified the mechanisms by which AM&AS was used for SCI treatment, namely, active ingredients, targets and signaling pathways. Consequently, further research into AM&AS treating SCI can be conducted on this scientific basis.

To explore the potential mechanism of complex rose-bergamot essential oil against anxiety accompanied with facial spots through network pharmacology.The components of rose and bergamot essential oils were determined by GC-MS and obtained from literature, and their action targets were predicted by PubChem, SwissADME and SwissTargetPrediction databases. Using "Anxiety disorder" and "Facial pigmentation" as keywords, the relevant targets of anxiety disorder and facial spots were mined in the databases of DrugBank, TTD, GeneCards, and OMIM. The intersection targets of complex rose-bergamot essential oil and anxiety accompanied with facial spots diseases were obtained by making Venn diagram, respectively. Protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of intersection targets were carried out through STRING platform, Metascape, and KEGG Mapper databases. The "complex essential oil- component- target- pathway" network was constructed by Cytoscape software. The key active compounds and core targets were docked by AutoDock software.A total of 34 active components of complex rose-bergamot essential oil and 405 corresponding targets were obtained. The intersection targets of complex essential oil with anxiety disorder and facial spot were 88 and 34, respectively, and the related KEGG pathways were 137 and 123 items, respectively. Neroli acetate, Neroli alcohol, and Linalool in complex rose-bergamot essential oil could play a therapeutic role in anxiety disorder by regulating key targets such as SLC6A4, GRIN2B and DRD2 to participate in the neuroactive ligand-receptor interaction and serotonergic synapse and other pathways, they also could play a role in the treatment of facial spots by regulating key targets such as EGFR, VEGFA, and PIK3CA in the PI3K-AKT, JAK-STAT and other signal pathways. The molecular docking between the key compounds and the core targets showed that the binding energy was less than 0 kcal /mol, indicating that the compound and the target could bind stably.Complex rose-bergamot essential oil can play a role in the treatment of anxiety disorder with facial spots through the synergistic mechanism of multicomponent, multitarget, and multipathway.

Background: Pulmonary hypertension (PH) is a complex disease caused by a wide range of underlying conditions, Tanshinone IIA (Tan IIA) has been widely used in PH patients. The study aimed to explore the possible molecular mechanism of Tan IIA against PH by network pharmacology and molecular docking. Methods: Tan IIA and PH-related targets were retrieved from public databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein–protein interaction (PPI) network were used to investigate the protein targets and mechanism. The binding activity of core targets and Tan IIA were verified by molecular docking. Results: A total of 26 overlapping target proteins between Tan IIA and PH were screened. PPI network identified HSP90AA1, PTPN11, ATM, CA2, TERT, PRKDC, and APEX1 as key pharmacological targets. The results of GO function enrichment analysis included regulation of smooth muscle cell proliferation and migration, regulation of mitotic cell cycle, and regulation of G1/S transition of mitotic cell cycle. KEGG pathway analysis showed that nitrogen metabolism, NF-kappa B signaling pathway, cell cycle, necroptosis, apoptosis, and JAK-STAT signaling pathway were associated with Tan IIA in PH. The molecular docking results showed that Tan IIA can closely bind three core targets (HSP90AA1, PTPN11, and CA2). Conclusions: The present work initially clarified the effective therapeutic targets, biological processes, and signaling pathways of Tan IIA treatment of PH, which lay a foundation for further research on the pharmacological effects of Tan IIA.

North Patrininae herba, a perennial herbaceous plant, has long been used in traditional Chinese medicine to treat appendicitis, enteritis, and dysentery. Sonchus arvensis L., Sonchus oleraceus L., and Ixeris chinensis (Thunb.) Nakai are used as substitutes for North Patrininae in different regions, but the consistency of chemical composition and efficacy of these three species is still unknown. In this study, a detailed chemical analysis was carried out of the extract obtained from Sonchus arvensis L., Ixeris chinensis (Thunb.) Nakai and Sonchus oleraceus L. and a chemical component not previously reported in Ixeris chinensis (Thunb.) Nakai was found-Luteolin-7-O-(6''-malonylglucoside). The mechanism of action of the extract against inflammation and type II diabetes was investigated using network pharmacology and analysis of blood-absorbed components following oral dosing of rats. Finally, a highly accurate and reliable method was established for quality control purposes. The results showed that Sonchus arvensis L. and Sonchus oleraceus L. may be considered potential resources of a medicinal compound, whereas Ixeris chinensis (Thunb.) Nakai requires further evaluation.

Traumatic brain injury (TBI) is characterized by cellular damage and inflammation in lesioned brain tissue. Ferulic acid has been shown to have a melioration effect on neurological functions. However, the active pharmacological effects and the underlying mechanisms of ferulic acid against TBI remain unclear. On the basis of network pharmacology and molecular docking methodology, this study aimed to investigate the beneficial effects of ferulic acid in treating TBI, and characterized the detailed biotargets and mechanisms of these actions. The identified core targets were validated via in silico simulation. We identified 91 overlapping targets associated with ferulic acid and TBI. In-silico simulation analysis validated the putative core targets of tumor protein p53, mitogen-activated protein kinase (MAPK) 1, and estrogen receptor 1. The Gene Ontology-enriched annotations and findings were largely associated with cell proliferation, apoptosis, and inflammation in nerve cells. Additional Kyoto Encyclopedia of Genes and Genomes enrichment analysis unmasked the pharmacological pathways of ferulic acid in treating TBI, including the MAPK signaling pathway and hypoxia-inducible factor-1 signaling pathway. Bioinformatic analyses and findings provide a new preclinical strategy for revealing the core targets and network pathways of ferulic acid in treating TBI. Moreover, some bioinformatic findings were computationally validated in silico for exhibiting the neuroprotective action of ferulic acid against TBI.

Acute lung injury (ALI) is a respiratory disease with high morbidity and mortality rates and is the primary cause of death in children and the elderly around the world. The use of Chinese foods in the complementary and alternative treatment of ALI has attracted more and more attention. This study aimed to explore the anti-ALI activity of Chinese functional foods Rosa roxburghii Tratt fruit polyphenols (RRTP). RRTP was administered to lipopolysaccharide-induced ALI mice, and its protective effects were comprehensively evaluated by lung histopathological examination, wet/dry (W/D) ratio, and cytokine production. Metabolomics analysis was used to identify the differential metabolites and metabolic pathways in plasma, and molecular docking and systemic biology-based network pharmacology assay were performed to explore the active components and potential therapeutic targets. The results indicated that RRTP significantly attenuated the severity of pathological changes and pulmonary capillary permeability. Furthermore, RRTP limited the increase in tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6) levels and the decrease in interleukin 10 (IL-10) levels in ALI mice. Metabolomics studies revealed that RRTP markedly affected 19 different metabolites, three amino acid metabolism pathways, and sphingolipid metabolism. Moreover, network pharmacology identified AKT1 (AKT serine/threonine kinase 1), TP53, IL-6, VEGFA (vascular endothelial growth factor A), and TNF (tumor necrosis factor) as the most promising target proteins, while quercetin, luteolin, and kaempferol were the core active components of RRTP. This study investigated the complex mechanisms of RRTP against ALI for the first time, and provided a foundation for the application of RRTP as a functional food, facilitating the research of nutritional food additives for the adjuvant treatment of ALI.

Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD’s pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure.

Objective. This study aimed to determine the active components of Zhinao capsule (ZNC) and the targets in treating Alzheimer’s disease (AD) so as to investigate and explore the mechanism of ZNC for AD. Methods. The active components and targets of ZNC were determined from the traditional Chinese medicine systems pharmacology database (TCMSP). The target genes of AD were searched for in GeneCards. Cytoscape was used to construct an herb-component-target-disease network. A protein-protein interaction (PPI) network was constructed by STRING. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the OmicShare. UCSF Chimera and SwissDock were used for molecular docking verification. Finally, four key target genes were validated by Western blotting. Results. In total, 55 active components, 287 targets of active components, 1197 disease genes, and 134 common genes were screened, which were significantly enriched in 3975 terms of biological processes (BP), 284 terms of cellular components (CC), 433 terms of molecular functions (MF), and 245 signaling pathways. Caspase-3 (CASP3) and beta-sitosterol, tumor necrosis factor-alpha (TNF-α) and quercetin, vascular endothelial growth factor A (VEGFA) and baicalein, and mitogen-activated protein kinase 1 (MAPK1) and quercetin showed good-to-better docking. Moreover, ZNC not only downregulated CASP3 and TNF-α protein expression but also upregulated the protein expression of VEGFA and MAPK1. Conclusions. The active components of ZNC, such as beta-sitosterol, quercetin, and baicalein may act on multiple targets like CASP3, VEGFA, MAPK1, and TNF-α to affect T cell receptor (TCR), TNF, and MAPK signaling pathway, thereby achieving the treatment of AD. This study provides a scientific basis for further exploring the potential mechanism of ZNC in the treatment of AD and a reference for its clinical application.

Age-related central neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are a rising public health concern and have been plagued by repeated drug development failures. The complex nature and poor mechanistic understanding of the etiology of neurodegenerative diseases has hindered the discovery and development of effective disease-modifying therapeutics. Quantitative systems pharmacology models of neurodegeneration diseases may be useful tools to enhance the understanding of pharmacological intervention strategies and to reduce drug attrition rates. Due to the similarities in pathophysiological mechanisms across neurodegenerative diseases, especially at the cellular and molecular levels, we envision the possibility of structural components that are conserved across models of neurodegenerative diseases. Conserved structural submodels can be viewed as building blocks that are pieced together alongside unique disease components to construct quantitative systems pharmacology (QSP) models of neurodegenerative diseases. Model parameterization would likely be different between the different types of neurodegenerative diseases as well as individual patients. Formulating our mechanistic understanding of neurodegenerative pathophysiology as a mathematical model could aid in the identification and prioritization of drug targets and combinatorial treatment strategies, evaluate the role of patient characteristics on disease progression and therapeutic response, and serve as a central repository of knowledge. Here, we provide a background on neurodegenerative diseases, highlight hallmarks of neurodegeneration, and summarize previous QSP models of neurodegenerative diseases.

Yi-Qi Cong-Ming (YQCM) decoction has been widely used to prevent age-related hearing loss (ARHL), the most prevalent neurodegenerative disease in the elderly.To explore the mechanism of YQCM decoction in the treatment of ARHL.The chemical constituents of YQCM were screened from the Traditional Chinese Medicine Systems Pharmacology Database. Potential targets of YQCM against ARHL were predicted by DrugBank, GeneCards, and OMIM database. Protein-protein network and enrichment analysis were used for exploring possible molecular mechanisms. Molecular docking and anThe main compounds have good affinities with hub targets, especially AKT1, PTGS2, and CASP3. GO and KEGG analysis showed that the main biological process and key targets were related to negative regulation of the apoptotic process. HOur study suggested that YQCM prevents ARHL by modulating the apoptosis process in auditory hair cells. Moreover, this study proved that bioinformatics analysis combined with molecular docking and cell model is a promising method to explore other possible pharmacological interventions of ARHL.

Zhishi Rhubarb Soup (ZRS) is a traditional Chinese medicine formula used in the clinic to treat acute cerebral infarction (ACI) for many years. However, the exact mechanism of the treatment remains unclear.This study elucidates the multitarget mechanisms underlying the effects of ZRS on ACI using network pharmacology analysis and verify its effect by performing animal experiments.Using the network pharmacology approach, the multiple components, critical targets and potential mechanisms of ZRS against ACI were investigated. Six herbal names of ZRS and 'acute cerebral infarction' were used as keywords to search the relevant databases. In addition, we established the MCAO model to verify the results of network pharmacology enrichment analysis. ZRS (10 g crude drug/kg) was gavaged once per day for 7 consecutive days beginning 3 h after model establishment. After ZRS treatment, TTC staining, Western blot analysis, IHC and ELISA were conducted to further explore the mechanism of ZRS intervention in ACI.The network pharmacology approach identified 69 key targets, 10 core genes and 169 signalling pathways involved in the treatment of ACI with ZRS.This study demonstrated that ZRS improved cerebral ischaemic injury by inhibiting neuroinflammation partly via the AGE-RAGE signalling pathway. It provides a theoretical basis for the clinical application of ZRS in the treatment of ACI.

Background. Modified Sanmiaosan is an effective cure in the treatment of ulcerative colitis, but its mechanisms of action remain unclear. This study revealed the pharmacological mechanisms of Modified Sanmiaosan acting on ulcerative colitis through a pharmacology approach. Materials and Methods. The active compounds and the targets of Modified Sanmiaosan were selected from the Traditional Chinese Medicine Systems Pharmacology database according to the absorption and metabolism. The UC-related therapeutic targets were collected from the PharmGKB database, the GeneCards database, the GADA database, and the OMIM database. The networks of “drug-component-target-disease” and “herbal-component-target” were constructed by the Cytoscape software. Protein–protein interaction network was generated by the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by the R software. Molecular docking technology was used to identify the affinity and activity between active compounds and targets. Results. The 80 effective ingredients of MSM were collected. A total of 5180 UC-related genes and the 153 key targets of MSM and UC-related were obtained. JUN, Akt1, and MAPK1 were identified as the “hub targets” involved in the effects of Modified Sanmiaosan on ulcerative colitis. Hub targets were mainly involved in inflammatory response and oxidative stress. As the results of GO analysis, biological processes such as DNA-binding transcription and RNA polymerization may participate in the treatment process; KEGG pathway analysis showed that hub targets were mainly involved in IL-17 signal pathway and TNF signal pathway of ulcerative colitis. The high affinity and activity of the active compounds and targets were verified through molecular docking. Conclusion. These findings demonstrate the active ingredients in Modified Sanmiaosan reduce inflammatory response by TNF and IL-17 signaling pathways to treat ulcerative colitis. Anti-inflammation and immune regulation may be the main mechanism of Modified Sanmiaosan in the treatment of ulcerative colitis. This study not only provide new insights into the development of a natural therapy for the prevention and treatment of ulcerative colitis but also proves a feasible method for discovering potential activated compounds from Chinese herbs.

Many multi-genic systemic diseases such as neurological disorders, inflammatory diseases, and the majority of cancers do not have effective treatments yet. Reinforcement learning powered systems pharmacology is a potentially effective approach to designing personalized therapies for untreatable complex diseases.In this survey, state-of-the-art reinforcement learning methods and their latest applications to drug design are reviewed. The challenges on harnessing reinforcement learning for systems pharmacology and personalized medicine are discussed. Potential solutions to overcome the challenges are proposed.In spite of successful application of advanced reinforcement learning techniques to target-based drug discovery, new reinforcement learning strategies are needed to address systems pharmacology-oriented personalized

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women, potentially causing ovarian infertility for women at gestational age. Huatan Tongjing Decoction is commonly used to treat PCOS; however, the involved molecular mechanism has not been fully understood. In this study, the active components of Huatan Tongjing Decoction and potentially targeted proteins were downloaded from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. PCOS-related genes were accessed from Malacards database. STRING database was utilized to construct a protein-protein interaction (PPI) network based on the PCOS-related genes and the predicted targets. Subsequently, the PPI network was subjected to Random walk with restart (RWR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on top 50 genes with the high affinity scores to the drug targets. Subsequently, based on the predicted drug components and targets, a component-gene interaction network was constructed. Finally, the most central drug targets were selected, and the corresponding compounds were subjected to molecular docking and dynamic simulations to examine their bindings. The 122 main active components and 246 potential targets of Huatan Tongjing Decoction were obtained from TCMSP, and a total of 259 nodes and 1919 interactions were acquired from the PPI network. The top 50 genes were mainly enriched in response to peptide hormone function and PI3K-Akt signaling pathway. Molecular docking and dynamic simulations predicted that MMP-quercetin interaction played an important role in the treatment of PCOS using Huatan Tongjing Decoction. Luteolin and quercetin in Huatan Tongjing Decoction potentially bound MMP9 and served as active components. This study preliminarily suggested the efficacy of Huatan Tongjing Decoction against PCOS in molecular degree.

To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation.The predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)‍-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-‍α (PFT-‍α) and GSK690693 for further investigation.The 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-‍α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated.Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.

Background Rumex japonicus Houtt (R. japonicus) is used mainly to treat various skin diseases in Southeast Asia. However, there are few studies on its quality evaluation methods and antifungal activity. Objective To establish the quality control criteria for the effective parts from R. japonicus against psoriasis. Methods High-performance liquid chromatography (HPLC) was established for its fingerprint, and the similarity evaluation, cluster analysis (CA) and principal component analysis (PCA) were used to reveal the differences of those fingerprints among the tested R. japonicus. Network pharmacology analyzed the relationship between the components and psoriasis, revealing the potential targets of R. japonicus. Oxford cup anti-C. albicans experiment was used to verify the antifungal activity of R. japonicus. Results HPLC was developed for the R. japonicus fingerprint by optimizing for 10 batches of quinquennial R. japonicus from different habitats; the 18 common peaks were identified with 10 characteristic peaks such as rutin, quercetin, aloe-emodin, nepodin, emodin, musizin-8-O-β-D-glucoside, chrysophanol, emodin-8-O-β-D-glucopyranoside, chrysophanol-8-O-β-D-glucopyranoside, and aloin, respectively. The network pharmacology-based analysis showed a high correlation between R. japonicus and psoriasis, revealing the potential targets of R. japonicus. The oxford cup anti-Candida albicans experiment displayed a significant activity response to emodin-8-O-β-D-glucopyranoside and the ethyl acetate fraction of R. japonicus acidic aqueous extract. Conclusions A new and optimized HPLC method was created, and the research provides an experimental basis for the development of effective drugs related to C. albicans. Highlights The fingerprint of R. japonicus was organically combined with network pharmacology to further clarify its criteria for quality control.

Objectives. The Traditional Chinese Medicine (TCM) formula Yi-Fei-Jian-Pi-Tang (YFJPT) has been demonstrated effective against Corona Virus Disease 2019 (Covid-19). The aim of this article is to make a thorough inquiry about its active constituent as well as mechanisms against Covid-19 via TCM network pharmacology. Methods. All the ingredients of YFJPT are obtained from the pharmacology database of the TCM system. The genes which are associated with the targets are obtained by utilizing UniProt. The herb-target network is built up by utilizing Cytoscape. The target protein-protein interaction network is built by utilizing the STRING database and Cytoscape. The critical targets of YFJPT are explored by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results. The outcomes show that YFJPT might has 33 therapeutic targets on Covid-19, namely, interleukin 2 (IL2), heme oxygenase 1 (HMOX1), interleukin 4 (IL4), interferon gamma (FNG), α nuclear factor of kappa light polypeptide gene enhancer in Bcells inhibitor, alpha (NFKBIA), nuclear factor-k-gene binding (NFKB), nitric oxide synthase 3 (NOS3), intercellular adhesion molecule 1 (ICAM1), hypoxia inducible factor 1 subunit alpha (HIF1A), mitogen-activated protein kinase 3 (MAPK3), epidermal growth factor receptor (EGFR), interleukin 10 (IL10), jun proto-oncogene (JUN), C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 8 (CXCL8), tumor protein p53 (TP53), interleukin 1 beta (IL1B), AKT serine/threonine kinase 1 (AKT1), tumor necrosis factor (TNF), interleukin 6 (IL6), erb-b2 receptor tyrosine kinase 2 (ERBB2), RELA proto-oncogene (RELA), NF-κB subunit, caspase 8 (CASP8), peroxisome proliferator activated receptor alpha (PPARA), TIMP metallopeptidase inhibitor 1 (TIMP1), transforming growth factor beta 1 (TGFB1), interleukin 1 alpha (IL1A), signal transducer and activator of transcription 1 (STAT1), mitogen-activated protein kinase 8 (MAPK8), myeloperoxidase (MPO), matrix metallopeptidase 3 (MMP3), matrix metallopeptidase 1 (MMP1), and NFE2 like bZIP transcription factor 2 (NFE2L2). The gene enrichment analysis prompts that YFJPT most likely contributes to patients related to Covid-19 by regulating the pathways of cancers. Conclusions. That will lay a foundation for the clinical rational application and further experimental research of YFJPT.

Lung adenocarcinoma (LUAD) is one of the major causes of cancer death in the world. Studies show that the effective anticancer component in blister beetles is cantharidin, which can improve chemotherapy efficacy, median survival, and prognosis of LUAD. However, the antitumor mechanism of blister beetles has not been fully clarified. This study aimed to identify the key targets of the treatment of LUAD by blister beetles based on the principle of network pharmacology. An integrated approach including network pharmacology and a molecular docking technique was conducted, which mainly comprises target prediction, weighted gene correlation network analysis (WGCNA) analysis, network construction, gene ontology, and pathway enrichment analysis. 35 key targets were obtained and significantly associated with response to external stimuli, collagen binding, cyclin binding, organic acid binding, pyruvate metabolism, glycolysis, and amino acid biosynthesis pathways. Both LASSO regression and the RF model had a high predictive ability, and 9 candidate genes were screened, among which BIRC5 and PLK1 were the key targets for the treatment of LUAD by using blister beetles and showed significant survival significance. Cantharidin exerts its antitumor effects through 8 targets in 32 pathways, while BIRC5 and PLK1 have obvious survival significance.

Background/Aims. Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the most common autoimmune demyelinating diseases of the central nervous system (CNS), with some similar pathological and clinical features. Bu-Shen-Yi-Sui (BSYS) Capsule, a Chinese herbal prescription, has been shown to be a potential therapeutic agent for MS and NMO. However, its antidemyelination mechanism in inflammatory demyelinating diseases of the CNS has not been fully clarified. This study is aimed at exploring the key components and potential mechanism of BSYS in the treatment of CNS demyelinating disease (CNSD) based on network pharmacology. Methods. The potential active ingredients and corresponding potential targets of BSYS Capsule were obtained from the TCMSP, BATMAN-TCM, Swiss Target Prediction platform, and literature research. Disease targets of CNSD were explored through the GeneCards and the DisGeNET databases. The matching targets of BSYS in CNSD were identified from a Venn diagram. The protein-protein interaction (PPI) network was constructed using bioinformatics methods. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the mechanisms of BSYS. Furthermore, the neuroprotective effects of BSYS were evaluated using a cell model of hydrogen peroxide- (H2O2-) induced cell death in OLN-93 cells. Results. A total of 59 potential bioactive components of BSYS Capsule and 227 intersection targets were obtained. Topological analysis showed that AKT had the highest connectivity degrees in the PPI network. Enrichment analysis revealed that the targets of BSYS in the treatment of CNSD were the PI3K-Akt and MAPK signaling pathway, among other pathways. GO analysis results showed that the targets were associated with various biological processes, including apoptosis, reactive oxygen species metabolic process, and response to oxidative stress, among others. The experimental results demonstrated that BSYS drug-containing serum alleviated the H2O2-induced increase in LDH, MDA, and ROS levels and reversed the decrease in SOD and mitochondrial membrane potential induced by H2O2. BSYS treatment also decreased the number of TUNEL (+) cells, downregulated Bcl-2 expression, and upregulated Bax and c-caspase-3 expression by promoting Akt phosphorylation. Conclusion. BSYS Capsule alleviated H2O2-induced OLN-93 cell injury by increasing Akt phosphorylation to suppress oxidative stress and cell apoptosis. Therefore, BSYS can be potentially used for CNSD treatment. However, the results of this study are only derived from in vitro experiments, lacking the validation of in vivo animal models, which is a limitation of our study. We will further verify the underlying mechanisms of BSYS in animal experiments in the future.

Background: This study aimed to clarify the mechanism of action of Qiangli Wuhu Mixture used in the treatment of pneumonia.Methods: The potential targets of Qiangli Wuhu Mixture in the treatment of pneumonia were predicted by network pharmacology. ICR male mice were randomly divided into 5 groups: normal control (Control), pneumonia model (Vehicle), low and high dose groups of Qiangli Wuhu Mixture, and dexamethasone positive control group with 12 mice in each. The model was established by tracheal instillation of lipopolysaccharide for 3 consecutive days. After the establishment of the animal model, Qiangli Wuhu Mixture was intragastrically administered for 5 days; the expression of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and anti-inflammatory factor interleukin-10 (IL-10) in the serum of mice in each group was detected by ELISA kit; the protective effect of Qiangli Wuhu Mixture on the lung tissue of pneumonia mice was observed by staining; Western Blot was used to detect the expression of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB) and NLRP3 signal pathway related proteins in lung tissue.Results: Network pharmacology predicted that the target of Qiangli Wuhu Mixture in treating pneumonia might be related to lipopolysaccharide reaction and Toll-like receptor signaling pathway. the in vivo results indicated that Qiangli Wuhu Mixture had a strong protective effect on acute pneumonia in mice induced by lipopolysaccharide, decreased the levels of inflammatory factors TNF-α, IL-1β and IL-6 in serum of model mice, and decreased the activation of TLR4, NF- κ B, and the expression of NLRP3 protein in lung tissue. Conclusion: Qiangli Wuhu Mixture has a strong protective effect on lipopolysaccharide-induced pneumonia in mice, and its mechanism of action may be related to reducing the pathological changes of lung tissue, reducing the level of inflammatory cytokines in blood, and inhibiting the inflammatory signal pathway of TLR4/NF-κB/NLRP3.

Fufang Zhenshu Tiaozhi (FTZ) has been widely used in clinical practice and proven to be effective against aging-induced osteoporosis in mice. This study aimed to explore the mechanism of FTZ against osteoclastogenesis and ovariectomized-induced (OVX) bone loss through the network pharmacology approach. The ingredients of FTZ were collected from the previous UPLC results, and their putative targets were obtained through multiple databases. Differentially expressed genes (DEGs) during osteoclastogenesis were identified through multi-microarrays analysis. The common genes between FTZ targets and DEGs were used to perform enrichment analyses through the clusterProfier package. The affinity between all FTZ compounds and enriched genes was validated by molecular docking. The effects of FTZ on osteoclastogenesis and bone resorption were evaluated by TRAP staining, bone resorption assay and RT-qPCR

Objective. To explore the mechanism of action of the yin nourishing and heat clearing prescription in treating cough variant asthma (CVA) based on network pharmacology (NP). Methods. The active ingredients and targets of the yin nourishing and heat clearing prescription were screened using the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP); CVA targets were screened by the GeneCards, NCBI gene, and OMIM databases to construct the component-target network and the protein-protein interaction (PPI) network. GO functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the target genes were performed to construct the component-disease-pathway-target biological network. Moreover, CVA-related core target structures with high values were subjected to molecular docking (MD) with the active components. Results. We found 265 eligible targets in the prescription and 1115 CVA-related genes. The medicine targets were intersected with disease targets, which yielded 148 common targets. After topology analysis, 66 key targets were screened. Upon GO functional annotation, 2408 biological processes, 153 molecular functions, and 162 KEGG pathways were enriched. Molecular docking results suggested that the major active ingredients of the prescription showed high affinity to the key targets, among which AKT1 might be the most important target. Conclusions. Active ingredients might act on AKT1, IL-6, VEGFA, IL-1B, and JUN to suppress eosinophil accumulation, decrease histamine release, suppress airway inflammation, regulate the airway immune microenvironment, increase autophagy in lung tissue, inhibit mucus production, and reduce airway resistance and hyperresponsiveness, thus treating CVA. Our findings provide a reference for further research and clinical applications of the prescription.

Background. Alzheimer’s disease places a heavy economic burden to healthcare systems around the world. However, the effective treatments are still lacking. Traditional Chinese medicines (TCM) of Schisandra chinensis and Acorus tatarinowii Schott have the pharmacological effects of sedation and neuroprotection and have been clinically proven to be effective in the treatment of AD. However, their main anti-Alzheimer’s compounds and functional mechanisms remain unclear. Purpose. To elucidate the main therapeutic components and possible mechanisms of Sc-At in AD using a comprehensive strategy combining metabolomics and network pharmacology. Methods. First, the UPLC-QTOF/MS method was used to identify the main chemical constituents of Schisandra chinensis and Acorus tatarinowii Schott alcohol extracts in vitro and in vivo. Secondly, the theoretical active ingredients, targets, and pathways of Sc-At for AD treatment were predicted by network pharmacology methods. Finally, plasma metabolomics were detected by UPLC-QTOF/MS to analyze the differential metabolites and metabolic pathways related to Sc-At. Based on the analyses above, the anti-AD mechanism of Sc-At was explored. Results. A total of 95 chemical components were identified in Sc-At extracts in vitro, and 34 prototype drug components were detected in rat plasma; network pharmacology screening identified 14 drug components in line with the principle of Lipinski, of which 10 were present for in vitro drug composition analysis. For these 10 components, 58 AD disease targets were predicted, and 85 AD-related KEGG signaling pathways were enriched. Six core biomarkers of Sc-At (cis-8,11,14,17-eicosatetraenoic acid, prostaglandin H2, sphingosine 1-phosphate, enol-phenylpyruvate, 3-methoxytyrosine, and pristanoyl-CoA) were regulated to a normal state during the treatment of AD. Conclusion. The mechanism of Sc-At for the treatment of AD can be achieved by the effect of the 10 compounds of Sc-At on TNF, MAPK8, MAPK14, PTGS1, and other targets, thereby affecting arachidonic acid metabolism, neurotransmitters, and sphingolipid metabolism.

Introduction The chronicity of advanced glycation end-products (AGEs) imparts various damages resulting in metabolic dysfunction and diseases involving inflammation and oxidative stress. The use of plant extracts is of high interest in complementary medicine. Yet, extracts are multicomponent mixtures, and difficult to pinpoint their exact mechanism. Objectives We hypothesise that network pharmacology and bioinformatics can help experimental findings depict the exact active components and mechanism of action by which they induce their effects. Additionally, the toxicity and variability can be lowered and standardised with proper encapsulation methods. Methodology Here, we propose the formulation of phytoniosomes encapsulating two Artemisia species (Artemisia dracunculus and Artemisia absinthium) to mitigate AGEs and their induced cell redox dysregulation in the liver. Extracts from different solvents were identified via liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS/MS). Phytoniosomes were explored for their anti-glycating effect and modulation of AGE-induced damages in THLE-2 liver cells. Network pharmacology tools were used to identify possible targets and signalling pathways implicated. Results Data demonstrated that A. absinthium phytoniosomes had a significant anti-AGE effect comparable to reference molecules and higher than A. dracunculus. They were able to restore cell dysfunction through the restoration of tumour necrosis alpha (TNF-alpha), interleukin 6 (IL-6), nitric oxide, and total antioxidant capacity. Phytoniosomes were able to protect cells from apoptosis by decreasing caspase 3 activity. Network pharmacology and bioinformatic analysis confirmed the induction of the effect via Akt-PI3K-MAPK and AGE-RAGE signalling pathways through quercetin and luteolin actions. Conclusion The current report highlights the potential of Artemisia phytoniosomes as strong contenders in AGE-related disease therapy., Scientific and Technological Research Council of Turkey TUBITAK [120Z200]; Projets de Recherche-Formation Universitaire (PRFU) [D01N01UN160420180008], This project was funded by The Scientific and Technological Research Council of Turkey TUBITAK (120Z200). The current project was partially supported by the Projets de Recherche-Formation Universitaire (PRFU) (D01N01UN160420180008).