Search

In the current study, bioinformatics analysis of the hepatocellular carcinoma (HCC) dataset was conducted with the hepatoprotective effect of the Fuzheng Huayu (FZHY) capsule against the diethylnitrosamine-induced HCC progression analyzed. Eight cell clusters were defined and tanshinone IIA, arachidonic acid, and quercetin, compounds of the FZHY capsule, inhibit HCC progression-related fibrosis by regulating the expression of PLAU and IGFBP3. Combined with the ameliorative effect of the FZHY capsule against liver dysfunctions and expression of PLAU and IGFBP3, our study confirmed the effect of the FZHY capsule on inhibiting the fibrosis-associated HCC progression via regulating the expression of PLAU and IGFBP3. [ABSTRACT FROM AUTHOR]

Asthma is a complex heterogeneous and inflammatory disease with an increasing incidence worldwide. Here, UHPLC-Q-Exactive-MSE analysis revealed that 21 alkaloids and 1 coumarin compound (Scopoletin) were identified in SDLTAs. In mouse model, SDLTAs treatment reduced the airway pathological damage, the levels of IL-4, IL-5, IgE, MUC5AC, and splenic index. In cell model, SDLTAs treatment significantly decreased IL-6, IL-8, MUC5AC, and mucus secretion induced by LPS. Network pharmacology studies revealed that the main active ingredients of SDLTAs, including oxysophoridine, oxymatrine, scopoletin and sophoridine, target TLR4, DPP4, IL6 and TNF, as well as regulate IL-17 signaling pathway, TNF signaling pathway, and toll-like receptor signaling pathway, leading to relief of asthma on an inflammatory basis. Docking results showed that the binding energy of the main active ingredients of SDLTAs to TLR4 and MyD88 varied from −5.38 kcal/mol to −4.01 kcal/mol. Further, SDLTAs down-regulated the expression of TLR4, MyD88 and p-c-Jun.

Kai Chen,1 Yaohui Yu,1 Yishu Wang,1 Yi Zhu,1 Chaoren Qin,1 Jintao Xu,1 Xiangjie Zou,2 Tianqi Tao,1 Yang Li,1 Yiqiu Jiang1 1Department of Sports Medicine and Joint Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yiqiu Jiang, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, People’s Republic of China, Email jyq_3000@163.comBackground: Astragalus membranaceus (AM) shows promise as a therapeutic agent for osteoarthritis (OA), a debilitating condition with high disability rates. OA exacerbation is linked to chondrocyte ferroptosis, yet the precise pharmacological mechanisms of AM remain unclear.Methods: We validated AM’s protective efficacy in an anterior cruciate ligament transection (ACLT) mouse model of OA. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database was utilized to identify AM’s active components and their targets. FerrDb (a database for regulators and markers of ferroptosis and ferroptosis-disease associations) pinpointed ferroptosis-related targets, while GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), Therapeutic Target Database (TTD), and DrugBank sourced OA-related genes. Molecular docking analysis further validated these targets. Ultimately, the validation of the results was accomplished through in vitro experiments.Results: AM exhibited anabolic effects and suppressed catabolism in OA chondrocytes. Network pharmacology identified 19 common genes, and molecular docking suggested quercetin, an AM constituent, interacts with key proteins like HO-1 and NRF2 to inhibit chondrocyte ferroptosis. In vitro experiments confirmed AM’s ability to modulate the NRF2/HO-1 pathway via quercetin, mitigating chondrocyte ferroptosis.Conclusion: This study elucidates how AM regulates chondrocyte ferroptosis, impacting OA progression, providing a theoretical basis and experimental support for AM’s scientific application.Keywords: systematic pharmacology, osteoarthritis, ferroptosis, Astragalus membranaceus, quercetin

Metformin (Met), a first-line management for type 2 diabetes mellitus, has been expansively employed and studied with results indicating its therapeutic potential extending beyond glycemic control. Beyond its established role, this therapeutic drug demonstrates a broad spectrum of action encompassing over 60 disorders, encompassing metabolic conditions, inflammatory disorders, carcinomas, cardiovascular diseases, and cerebrovascular pathologies. There is clear evidence of Met's action targeting specific nodes in the molecular pathways of these diseases and, intriguingly, interactions with the intestinal microbiota and epigenetic processes have been explored. Furthermore, novel Met derivatives with structural modifications tailored to diverse diseases have been synthesized and assessed. This manuscript proffers a comprehensive thematic review of the diseases amenable to Met treatment, elucidates their molecular mechanisms, and employs informatics technology to prospect future therapeutic applications of Met. These data and insights gleaned considerably contribute to enriching our understanding and appreciation of Met's far-reaching clinical potential and therapeutic applicability. [ABSTRACT FROM AUTHOR]

Objective: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. Methods: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. Results: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. Conclusion: Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways. [ABSTRACT FROM AUTHOR]

Context The mechanism of tetrandrine (TET) in hepatocellular carcinoma (HCC) progression and sorafenib (Sora) chemosensitivity deserves investigation. Objective Using network pharmacology approaches to elucidate the mechanisms of TET in HCC. Materials and methods CCK-8, colony formation, and flow cytometry assays were used to measure cell phenotypes. BALB/c nude mice were divided into Control, Sora (10 mg/kg), TET (50 mg/kg), and TET + Sora (10 mg/kg Sora plus 50 mg/kg TET) groups to evaluate the antitumor effects of TET for 21 days. Sora and TET were given by intraperitoneal injection or oral gavage. Results For SMMC7721 (IC50 = 22.5 μM) and PLC8024 (IC50 = 18.4 μM), TET (10, 20 μM) reduced colony number (0.68 ± 0.04- and 0.50 ± 0.04-fold, 0.56 ± 0.04- and 0.42 ± 0.02-fold), induced cell cycle arrest at G0/G1 stage (1.22 ± 0.03- and 1.39 ± 0.07-fold, 1.37 ± 0.06- and 1.55 ± 0.05-fold), promoted apoptosis (2.49 ± 0.26- and 3.63 ± 0.33-fold, 2.74 ± 0.42- and 3.73 ± 0.61-fold), and inactivated PI3K/AKT/mTOR signalling. Sora (10 μM) decreased cell proliferation, enhanced apoptosis, and inhibited PI3K/AKT/mTOR signalling, and these effects were further aggravated in the combination group. Activating PI3K/AKT/mTOR reversed the effects of TET on cell proliferation and Sora sensitivity. In the combination group, tumour volumes and weights were decreased to 202.3 ± 17.4 mm3 and 151.5 ± 25.8 mg compared with Sora (510.6 ± 48.2 mm3 and 396.7 ± 33.5 mg). Discussion and conclusions TET enhances Sora sensitivity by inactivating PI3K/AKT/mTOR, suggesting the potential of TET as a chemosensitizer in HCC.

[Display omitted] • UHPLC-Q-Exactive-MSE analysis revealed 23 compounds in SDLTAs. • SDLTAs reduced the overproduction of IL-4, IL-5, IgE and MUC5AC in asthmatic mice. • SDLTAs inhibited IL-6, IL-8 and MUC5AC expression in LPS-induced BEAS-2B cells. • Network pharmacology study predicted potential mechanism of SDLTAs against asthma. • SDLTAs regulated the activity of TLR4, Myd88 and p-c-Jun. Asthma is a complex heterogeneous and inflammatory disease with an increasing incidence worldwide. Here, UHPLC-Q-Exactive-MSE analysis revealed that 21 alkaloids and 1 coumarin compound (Scopoletin) were identified in SDLTAs. In mouse model, SDLTAs treatment reduced the airway pathological damage, the levels of IL-4, IL-5, IgE, MUC5AC, and splenic index. In cell model, SDLTAs treatment significantly decreased IL-6, IL-8, MUC5AC, and mucus secretion induced by LPS. Network pharmacology studies revealed that the main active ingredients of SDLTAs, including oxysophoridine, oxymatrine, scopoletin and sophoridine, target TLR4, DPP4, IL6 and TNF, as well as regulate IL-17 signaling pathway, TNF signaling pathway, and toll-like receptor signaling pathway, leading to relief of asthma on an inflammatory basis. Docking results showed that the binding energy of the main active ingredients of SDLTAs to TLR4 and MyD88 varied from −5.38 kcal/mol to −4.01 kcal/mol. Further, SDLTAs down-regulated the expression of TLR4, MyD88 and p-c-Jun. [ABSTRACT FROM AUTHOR]

Biatractylolide is an Atractylodes macrocephala derived bisesquiterpenoid that has been found treatment of dementia in model mice. This study aims to explore the therapeutic effect on vascular dementia. Network pharmacological techniques have been used to elaborate the involved mechanisms of biatractylolide treating vascular dementia. Based on PubChem database, Swiss target prediction and human gene database GeneCards, 19 common target molecules were screened, they were enriched in many biological, such as Alzheimer’s disease corrective pathway, pathways of neurodegeneration-multiple diseases, calcium signaling pathway, notch signaling pathway and vascular endothelial growth factor signaling pathway. Muscarinic acetylcholine receptor M1, amyloid-beta precursor protein, microtubule-associated protein tau, presenilin-1, presenilin-2, prostaglandin G/H synthase 2 and disintegrin, and metalloproteinase domain-containing protein 17 were enriched in Alzheimer’s disease corrective pathway. Protein–protein interaction network presents that six highest degree nodes, phosphoinositide-3-kinase regulatory subunit 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, Harvey rat sarcoma virus, Jun N-terminal kinases, catenin beta 1, mitogen-activated protein kinase 3 and tumor protein P53, play core role in vascular dementia and four molecules, mitogen-activated protein kinase 14, Janus kinase 2, amyloid-beta precursor protein and tyrosine-protein phosphatase non-receptor type 1, closely interact with biatractylolide. In addition, acetylcholinesterase was identified to have a strong interaction with biatractylolide. This study suggests that biatractylolide is a potential drug for treatment of vascular dementia or Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetes is a complex metabolic disease characterized by hyperglycemia, plaguing the whole world. However, the action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of diabetes mellitus. According to the previous research, the TCM of Polygonum multiflorum (PM) showed noteworthy hypoglycemic effect. Up to now, its hypoglycemic active ingredients and mechanism of action are not yet clear. In this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypoglycemic mechanism of PM. Methods First, the compounds with good pharmacokinetic properties were screened from the self-established library of PM, and the targets of these compounds were predicted and collected through database. Relevant targets of diabetes were summarized by searching database. The intersection targets of compound-targets and disease-targets were obtained soon. Secondly, the interaction net between the compounds and the filtered targets was established. These key targets were enriched and analyzed by protein–protein interactions (PPI) analysis, molecular docking verification. Thirdly, the key genes were used to find the biologic pathway and explain the therapeutic mechanism by genome ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis. Lastly, the part of potential bioactive compounds were under enzyme activity inhibition tests. Results In this study, 29 hypoglycemic components and 63 hypoglycemic targets of PM were filtrated based on online network database. Then the component-target interaction network was constructed and five key components resveratrol, apigenin, kaempferol, quercetin and luteolin were further obtained. Sequential studies turned out, AKT1, EGFR, ESR1, PTGS2, MMP9, MAPK14, and KDR were the common key targets. Docking studies indicated that the bioactive compounds could stably bind the pockets of target proteins. There were 38 metabolic pathways, including regulation of lipolysis in adipocytes, prolactin signaling pathway, TNF signaling pathway, VEGF signaling pathway, FoxO signaling pathway, estrogen signaling pathway, linoleic acid metabolism, Rap1 signaling pathway, arachidonic acid metabolism, and osteoclast differentiation closely connected with the hypoglycemic mechanism of PM. And the enzyme activity inhibition tests showed the bioactive ingredients have great hypoglycemic activity. Conclusion In summary, the study used systems pharmacology to elucidate the main hypoglycemic components and mechanism of PM. The work provided a scientific basis for the further hypoglycemic effect research of PM and its monomer components, but also provided a reference for the secondary development of PM.

Salvia miltiorrhiza and Radix Pueraria lobata herb pair is the core of the huoxuehuayu method to treat type 2 diabetes in Chinese. However, the mechanisms of this herb pair remain unclear. In this study, after fecal samples of rats were analyzed, 12 biomarkers and 15 pathways were identified by metabolomics. Then systematic pharmacology predicted 138 targets and 245 pathways. After combining these results with 3 overlapping pathways, a complete network was built. The 7 hub targets in it were verified by quantitative polymerase chain reaction (qPCR). Compared with the Model group, the mRNA level of ADCY2 (P＜0.05), MAOB, (P＜0.01), AKR1B1 (P＜0.05), XDH (P＜0.05), PDE3A (P＜0.05), and NOS2 (P＜0.01) were decreased, while the level of NOS3 (P＜0.05) was elevated after herb pair treatment. The results indicate treating effect of this herb pair is related to reducing oxidative stress, inflammation, and improving energy metabolism.

Objective To explore the active ingredients, targets and mechanisms of Osteoking(OK, Herbs of the Yi Minority in Yunnan Province) in the treatment of osteoporosis (OP) with the help of systematic pharmacology. And the molecular docking technology is used for docking verification. Methods Screened the active components and targets of OK through TCMSP. Queried GeneCard, OMIM, DisGeNet, TTD Databases to Screening of OP-related gene targets. Constructed the intersection gene target protein-protein interaction(PPI) network by using STRING and Cytoscape Software.The core targets were analyzed by GO and KEGG with the help of DAVID and KEGG Mapper database.Finally, Autodock was used for docking verification. Results The main active components such as quercetin, kaempferoland,11-octadecenoic acid,11-eicosenoic acid,ursolic acid,beta-sitosterol,tormentic acid were collected. It involves biological processes such as cell responses to lipids, toxic substances, lipopolysaccharides, bacterial molecules, inorganic substances, organic ring compounds, organic nitrogen compounds and so on.Theymight play rolesthrough PI3K-Akt, Ras, MAPK, ect multiple pathways.Molecular docking suggested that ursolic acid had better binding effect with AKT1, ALB and IL-6.Conclusion It is preliminarily clear that OK participates in promoting bone formation and inhibiting bone fracture through multi-targets and multi-pathways, which provides theoretical support and design ideas for further experimental research. [ABSTRACT FROM AUTHOR]

Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained.Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR.Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p < 0.05).Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study.

Background: Clinical research found that Hedysarum Multijugum Maxim. - Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained. Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC's potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC's targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR. Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p < 0.05). Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study. [ABSTRACT FROM AUTHOR]

Background: Xuefu Zhuyu decoration (XFZYD), as a traditional Chinese compound recipe, has been used to treat atherosclerosis cardiovascular disease (ASCVD) for thousands of years in China, but its effective compounds and underlying treatment molecular mechanism remains promiscuous, which severely limits its clinical application.Methods: The effective components and their targets of XFZYD were predicted and screened based on the Traditional Chinese Medicine System Pharmacology (TCMSP) database. The candidate therapeutic targets of ASCVD were screened by Pharmacogenomics Knowledgebase (PharmGKB) and Comparative Toxicogenomics Database (CTD). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Differentially expressed genes were identified using the GEO2R online tool. Molecular docking was performed by Schrodinger software. To assess the efficacy of the prediction, human umbilical vein endothelial cells (HUVECs) treated with the effective compound of XFZYD were used as the in vitro model.Results: A total of 108 effective compounds (including quercetin) and 137 candidate therapeutic targets were identified. Analyzing the relationships among effective compounds, candidate therapeutic targets, and signaling pathways, the therapy mechanisms of XFZYD were mainly reflected in the protection of vascular endothelium, anti-inflammatory, antioxidant stress, etc. Accordingly, we found the effective compound of XFZYD (quercetin) decreased intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expressions and pro-inflammatory cytokines in HUVECs treated with lipopolysaccharide (LPS), and reduced the adhesion function of HUVECs with monocytes. The inhibitor of the predicted target protein (PTGS2) could further reduce the expressions of VCAM-1, ICAM-1, and TNF-α induced by LPS, and inhibit the adhesion function of HUVECs with monocytes, while PTGS2 agonists partially counteracted the protective effect of quercetin.Conclusions: In this study, the effective components and potential therapeutic targets of XFZYD for ASCVD treatment were explored from the perspective of systemic pharmacology. The effective component quercetin was verified to protect endothelial cells by reducing endothelial inflammatory response and impeding the attachment of monocytes against the predicted therapeutic target PTGS2.

Metformin (Met), a first-line management for type 2 diabetes mellitus, has been expansively employed and studied with results indicating its therapeutic potential extending beyond glycemic control. Beyond its established role, this therapeutic drug demonstrates a broad spectrum of action encompassing over 60 disorders, encompassing metabolic conditions, inflammatory disorders, carcinomas, cardiovascular diseases, and cerebrovascular pathologies. There is clear evidence of Met's action targeting specific nodes in the molecular pathways of these diseases and, intriguingly, interactions with the intestinal microbiota and epigenetic processes have been explored. Furthermore, novel Met derivatives with structural modifications tailored to diverse diseases have been synthesized and assessed. This manuscript proffers a comprehensive thematic review of the diseases amenable to Met treatment, elucidates their molecular mechanisms, and employs informatics technology to prospect future therapeutic applications of Met. These data and insights gleaned considerably contribute to enriching our understanding and appreciation of Met's far-reaching clinical potential and therapeutic applicability., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Berberine (BBR) is the main component of Coptidis rhizoma, the dried rhizome of Coptis chinensis and is a potential plant alkaloid used for the treatment of cancer due to its high antitumor activity. The present study examined the therapeutic potential and molecular mechanism of action of BBR against HCC, using systematic pharmacology combined with a molecular docking approach and experimental validation in vitro. Through systematic pharmacological analysis, it was found that BBR serves a significant role in inhibiting HCC by affecting multiple pathways, especially the PI3K/AKT signaling pathway. Furthermore, the docking approach indicated that the binding of BBR to AKT could lead to the suppression of AKT activity. The present study examined the inhibitory effect of BBR on the PI3K/AKT pathway in HCC and identified that BBR downregulated the expressions of phosphorylated AKT and PI3K in MHCC97-H and HepG2 cells, inhibiting their growth, cell migration and invasion in a dose-dependent manner. In addition, inhibition of the AKT pathway by BBR also contributed to cell apoptosis in MHCC97-H and HepG2 cells. Taken together, the results of the present study suggested that BBR may be a promising antitumor drug for HCC that acts by inhibiting the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Gout is a chronic disease of deposition of monosodium urate crystals, characterised by hyperuricaemia and gouty arthritis, plaguing the whole world. Simiao Pill (SMP), a classic herbal formula, has been extensively used to treat arthritic symptoms in clinical practice in China for centuries. The action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of gout. However, the pharmacological mechanisms of SMP still remain vague to date. In this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypouricemic mechanisms of SMP. At first, we collected putative targets of SMP based on Traditional Chinese Medicine Systems Pharmacology Database databases, and relevant targets of gout were summarised by four searching database, including Disgenet, therapeutic target database, Online Mendelian Inheritance in Man, and Gene Cards. The putative targets of SMP and known therapeutic targets of gout built an interaction network, so the networks of compound targets and disease-targets were obtained soon. Then, the protein–protein interactions analysis and molecular docking verification were established. Finally, the key genes were used to find the biological pathway and explain the therapeutic mechanism by genome ontology and kyoto encyclopaedia of genes and genomes analysis. In our study, 30 hypouricemic components and 600 hypouricemic targets of SMP were filtrated based on an online network database. Then the component-target interaction network was constructed, 10 key components and 15 key targets were further obtained. Docking studies indicated that the bio-active compounds could stably bind the pockets of target proteins. Go enrichment and and kyoto encyclopaedia of Genes and genomes pathway analysis indicated that SMP had a strong integration with gout and hyperuricemia, which might significantly contribute to multiple therapeutic effect. In summary, this study used systems pharmacology to demonstrate the main components and mechanism of SMP in treating gout. Moreover, the work provided a scientific basis for the further effect research of SMP and its monomer components, but also provided a new therapeutic strategy in gout. [ABSTRACT FROM AUTHOR]

[Display omitted] • HPLC/LTQ-Orbitrap-MS negative and positive ion currents of DG. • LC-MS analyses of metabolic profiles. • The targets analysis related to potential biomarker. • Results of systematic pharmacology. • Study on the mechanism of DG on T2DM. The herbal pair of Salvia miltiorrhiza Bunge and Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (DG) is commonly used in the treatment of type 2 diabetes (T2DM) in traditional Chinese medicine (TCM). The drug pair DG was designed by Dr. Zhu chenyu to improve the treatment of T2DM. Aim: This study combined with systematic pharmacology and urine metabonomics to explore the mechanism of DG in the treatment of T2DM. Methods: The therapeutic effect of DG on T2DM was evaluated by fasting blood glucose (FBG) and biochemical indexes. Systematic pharmacology was used to screen the active components and targets that may be related to DG. Metabonomics was established to find urinary metabolites and pathways that may be induced by DG. Finally, integrate the results of these two parts for mutual verification. Results: FBG and biochemical indexes showed that DG could reduce FBG and adjust the related biochemical indexes. Metabolomics analysis indicated that 39 metabolites were related to DG for T2DM treatment. In addition, systematic pharmacology showed compounds and potential targets which were associated with DG. Finally, 12 promising targets were selected as targets for T2DM therapy by integrating the results. Conclusion: The combination of metabonomics and systematic pharmacology based on LC-MS is feasible and effective, which provides strong support for exploring the effective components and pharmacological mechanism of TCM. [ABSTRACT FROM AUTHOR]

Qingfei Paidu decoction (QFPDD) has been clinically proven to be effective in the treatment of coronavirus disease 2019 (COVID-19). However, the bioactive components and therapeutic mechanisms remain unclear. This study aimed to explore the effective components and underlying mechanisms of QFPDD in the treatment of COVID-19 by targeting the virus-host interactome and verifying the antiviral activities of its active components in vitro. Key active components and targets were identified by analysing the topological features of a compound-target-pathway-disease regulatory network of QFPDD for the treatment of COVID-19. The antiviral activity of the active components was determined by a live virus infection assay, and possible mechanisms were analysed by pseudotyped virus infection and molecular docking assays. The inhibitory effects of the components tested on the virus-induced release of IL-6, IL-1β and CXCL-10 were detected by ELISA. Three components of QFPDD, oroxylin A, hesperetin and scutellarin, exhibited potent antiviral activities against live SARS-CoV-2 virus and HCoV-OC43 virus with IC 50 values ranging from 18.68 to 63.27 μM. Oroxylin A inhibited the entry of SARS-CoV-2 pseudovirus into target cells and inhibited SARS-CoV-2 S protein-mediated cell-cell fusion by binding with the ACE2 receptor. The active components of QFPDD obviously inhibited the IL-6, IL-1β and CXCL-10 release induced by the SARS-CoV-2 S protein. This study supports the clinical application of QFPDD and provides an effective analysis method for the in-depth study of the mechanisms of traditional Chinese medicine (TCM) in the prevention and treatment of COVID-19. [Display omitted] • The active components of QFPDD were identified by targeting the virus-host interactome. • Three serum-absorbed components of QFPDD, oroxylin A, hesperetin and scutellarin, exhibit potent anti-SARS-CoV-2 activity. • Oroxylin A inhibits SARS-CoV-2 entry and S protein-mediated cell-cell fusion. • The active components of QFPDD inhibit the release of SARS-CoV-2 S protein-induced cytokines. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease that often results in joint destruction. Ershiwuwei Lvxue Pill (ELP), a prescription of Tibetan medicine, has been used for centuries for the clinical treatment of RA in Tibet, China. In a previous study, we reported that ELP could ameliorate RA symptoms in CIA rats by inhibiting the inflammatory response and inducing apoptosis in synovial tissues. It is still needed further to clarify the mechanisms of action of ELP in mitigating RA.Purpose: In this study, we aim to elucidate the mechanism of action of ELP to improve RA joint damage and explore the changes in the intestinal flora and host metabolites.Methods: Firstly, we analyzed the main absorbed constituents of ELP in the serum of rats by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF/MS). Then, we verified the alleviating effects of ELP on cartilage injury and bone erosion as well as the inflammatory response in CIA rats by microCT, H&E staining, safranin-O staining, and ELISA. Moreover, we investigated the main factors that mediate joint damage, including the production of matrix metalloproteinases (MMPs) and osteoclast activity in the ankle of rats by immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining. Further, we explored the molecular mechanisms of the MMPs production and osteoclast activity in CIA rats treated with ELP through various experiments such as ELISA, qRT-PCR, western blotting, and immunofluorescence assay. Besides, we investigated gut microbiota composition by 16S rDNA sequencing and serum metabolites through untargeted metabolomics. In addition, we analyzed the correlation between gut microbiota and metabolites by Spearman correlation analysis.Results: In this study, we identified 20 compounds from rat serum samples, which could be the ELP components that improve RA. Moreover, we found that ELP could alleviate cartilage and bone injury by reducing MMP-1, MMP-3, and MMP-13 expression and osteoclast activity in CIA rats. Further studies demonstrated that ELP could reduce joint damage by inhibiting osteoprotegerin (OPG)/receptor activator for nuclear factor-κB ligand (RANKL) /nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinases (JNK) signal pathways. The 16S rDNA sequencing analysis indicated that there was a significant difference in the gut microbiota composition between the normal and CIA rats, and these differences were changed after ELP administration. ELP could alter the gut microbiota by increasing the abundance of the genus Lactobacillus and decreasing the abundance of Dorea, [Eubacterium]_ventriosum_group, Anaerostipes, Collinsella, Coprococcus_1, Ruminiclostridium_5, Ruminococcus_1, Family_XIII_UCG-001, Butyricicoccus, Erysipelotrichaceae_UCG-003, Lachnoclostridium, Faecalibacterium, Lachnospiraceae_UCG-010, Roseburia, Rs-E47_termite_group_norank, Treponema_2 genera. Non-targeted metabolomics analysis showed that ELP reduced arachidonic acid levels. The serum arachidonic acid level was significantly correlated with the abundance of 41 genera, particularly Collinsella and Lactobacillus.Conclusion: Our study shows that ELP can improve RA joint damage by inhibiting MMPs production and osteoclast activity, and regulating intestinal flora and host metabolites, which provides a novel insight into the ELP in alleviating RA. [ABSTRACT FROM AUTHOR]

Coronary heart disease (CHD) and depression are very common and often co-existing disorders. Xiong-Pi-Fang (XPF), a therapeutic classical traditional Chinese medicine (TCM) formula, has shown satisfactory efficacy in treating CHD associated with depression. However, its mechanism of action is still unknown. To employ a systematic pharmacology approach for identifying the action mechanisms of XPF in treating CHD associated with depression. We used a systematic pharmacology approach to identify the potential active mechanisms of XPF in treating CHD with depression. Potential active compounds in XPF and the diseases targets were screened using relevant databases to build corresponding pathways, following the experiments that were conducted to confirm whether the presumptive results of systemic pharmacology were correct. Network pharmacology predicted 42 key targets and 20 signaling pathways involved in XPF-mediated treatment, with IL-6/JAK2/STAT3/HIF-1α/VEGF-A pathway significantly affected. The common influences were hypothalamic–pituitary–adrenal axis (HPA axis) and glucocorticoid signaling, validated through chronic unexpected mild stress (CUMS) with isoprenaline (ISO) for inducing CHD within the depression model in rats. In addition, XPF intake reduced depressive-like behaviors and improved ECG ischemic changes. Furthermore, XPF exerted some anti-inflammatory effects by inhibiting the interleukin-6 (IL-6) induced phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), ultimately downregulating hypoxia-inducible factor 1-α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) activation. The dysfunctional HPA axis feedback loop was also regulated, which enhanced the glucocorticoid receptor (GR) expression. In contrast, it improved glucocorticoid resistance by reducing the mineralocorticoid receptor expression. Suppressing IL-6 release and maintaining the HPA feedback loop balance could be the primary mechanism of XPF against CHD with depression. The significance of the IL-6 and HPA axis identified indicates their potential as essential targets for CHD therapy with depression. [Display omitted] • XPF regulates IL-6/JAK2/STAT3/HIF-1α/VEGF-A pathway and the HPA axis against CHD with depression. • Systematic pharmacology acts as an effective strategy for researching complex mechanisms disease. • TCM treatment of diseases is a multi-target comprehensive effect. • Our study provides a good model for TCM research. [ABSTRACT FROM AUTHOR]

[Display omitted] • DG is a famous TCM herb pair to treat T2DM. • DG makes changes of 12 biomarkers: alanine, n-butyrate, succinic acid, lactic acid, L-proline, valine, leucine, glutamate, glucose, isoleucine, α-ketoisovalerate, and hypoxanthine. • DG mainly functions through Purine Metabolism, Galactose Metabolism, and Arginine and Proline Metabolism pathways to treat T2DM. • DG adjust the mRNA levels of ADCY2, MAOB, AKR1B1, XDH, PDE3A, NOS2, and NOS3. Salvia miltiorrhiza and Radix Pueraria lobata herb pair is the core of the huoxuehuayu method to treat type 2 diabetes in Chinese. However, the mechanisms of this herb pair remain unclear. In this study, after fecal samples of rats were analyzed, 12 biomarkers and 15 pathways were identified by metabolomics. Then systematic pharmacology predicted 138 targets and 245 pathways. After combining these results with 3 overlapping pathways, a complete network was built. The 7 hub targets in it were verified by quantitative polymerase chain reaction (qPCR). Compared with the Model group, the mRNA level of ADCY2 (P＜0.05), MAOB, (P＜0.01), AKR1B1 (P＜0.05), XDH (P＜0.05), PDE3A (P＜0.05), and NOS2 (P＜0.01) were decreased, while the level of NOS3 (P＜0.05) was elevated after herb pair treatment. The results indicate treating effect of this herb pair is related to reducing oxidative stress, inflammation, and improving energy metabolism. [ABSTRACT FROM AUTHOR]

Leukemia is a common blood cancer, whose treatment usually necessitates chemo/radiotherapy and bone marrow transplant. Hence, safer and more effective options are urgently needed. Mylabris, the dried body of blister beetles, has been used extensively in traditional Chinese medicine. This study applied bioinformatics and systematic pharmacology to investigate the mechanism of action of mylabris in the treatment of leukemia. Five effective components and 35 corresponding target proteins were identified by screening the TCMSP database; whereas 776 genes related to leukemia were selected using OMIM, GeneCards, and the Therapeutic Target Database. Eight genes common to mylabris and leukemia were identified. Protein-protein interaction network analysis and a component-target-pathway diagram identified TP53 and PTEN as key gene targets of mylabris in the treatment of leukemia. GO enrichment analysis pointed to DNA damage and cell cycle disorder caused by p53 signaling as the most significant processes; whereas KEGG enrichment pointed to the p53 signaling pathway. In summary, mylabris may exert a therapeutic effect on leukemia by triggering DNA damage, inducing apoptosis, as well as inhibiting the growth and proliferation of tumor cells through the regulation of TP53 and PTEN . These findings provide a mechanistic rationale for the treatment of leukemia with traditional Chinese medicine.

Qiwei Putao powder (Uzhumu-7 in Mongolian) is a traditional Mongolian medicine, which has been widely used for alleviating cough and dyspnea, especially in aged individuals in both Inner Mongolia Autonomous Region and Xinjiang Uygur Autonomous Region of China. However, the active ingredients and exact pharmacological mechanism remain unclear. The protective effect of Qiwei Putao powder (QPP) on mice with cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced chronic obstructive pulmonary disease (COPD) was assessed by histopathological hematoxylin and eosin staining, lung coefficient determination and measurement of cytokine levels. The bioactive ingredients and potential targets of the QPP were screened and detected with network pharmacology method and ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). The mechanism and efficacy of active ingredients were further validated in COPD mice with immunohistochemistry tests, cytokine level measurement and RT-PCR. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) in the nucleus, interleukin (IL)-1β, superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA) kits to evaluate oxidative stress and inflammatory conditions in vivo after treatment. The expression of Nrf2 and downstream genes was detected by RT-PCR. QPP can alleviate pathological changes in the lung during COPD progression. Sixty-one bioactive molecules were identified in QPP, 42 candidate compounds present in UPLC-Q/TOF-MS and 30 predicted COPD-related targets were generated by in silico analysis. A therapeutic network was constructed with all potential targets to predict the preventive effects of the targets on respiratory disease as well as cardiovascular diseases, nervous system diseases, musculoskeletal diseases and bacterial infections. Targets related to inflammation, immunity and oxidative stress (prostaglandin-endoperoxide synthase 2, PTGS2; Nrf2; heat shock protein 90 alpha class A1, HSP90AA1; nitric oxide synthase, NOS2A; etc.) influenced COPD progression the most. We found that Nrf2 promotes a cell antioxidant response and is a key common target in the response to treatment with isoliquiritigenin (ISL), pterostilbene (PTE) and quercetin (QUE), the highly absorbed active ingredients in the formula. The data showed a strong synergistic protective role of these three molecules against the death of human type II alveolar adenocarcinoma (A549) cells through Nrf2 activation following H 2 O 2 exposure and provide pharmacological mechanism of QPP in COPD treatment. Image 1 [ABSTRACT FROM AUTHOR]

Radix Angelicae biseratae is a widely used Chinese traditional herbal medicine for osteoarthritis (OA). Its therapeutic efficacy has been confirmed in clinical practice. However, its mechanisms of action in treating OA have remained elusive. The purpose of the present study was to identify active components with good oral bioavailability and drug-like properties from Radix Angelicae biseratae through systematic pharmacology and in vitro experiments to determine targets of Radix Angelicae biseratae in the treatment of OA. The functional components of Radix Angelicae biseratae were screened from the Traditional Chinese Medicine Systems Pharmacology database based on oral bioavailability and drug-like properties. Subsequently, the databases STITCH, Open Targets Platform and DrugBank were searched and microarray analysis was performed to screen the active components of Radix Angelicae biseratae to treat OA and predict its potential target proteins. The interaction network and protein interaction network were then generated and examined, molecular docking between active components and targets was performed and the enrichment of potential target proteins was analyzed. Finally, reverse transcription-quantitative (RT-q)PCR and western blot analyses were used to verify the therapeutic effect of Radix Angelicae biseratae extract on the expression of OA-associated target proteins. The results provided eight active components in Radix Angelicae biseratae, which were firmly linked to 20 targets of OA. In combination with molecular docking and the analysis of the interaction network between components and targets, it was suggested that sitosterol was a major active component of Radix Angelicae biseratae in the treatment of OA. Protein interaction network analysis suggested that prostaglandin-endoperoxide synthase 2 (PTGS2), nitric oxide synthase 3 and cytochrome P450 2B6 may be critical targets for Radix Angelicae biseratae in the treatment of OA. In addition, RT-qPCR and western blot analyses suggested that Radix Angelicae biseratae extract inhibited the mRNA and protein expression of PTGS2 in degenerative articular cartilage cells in vitro, whilst other targets remain to be verified. Functional enrichment analysis indicated that Radix Angelicae biseratae confers pharmacological efficacy towards OA through exerting anti-inflammatory effects and immune regulation. [ABSTRACT FROM AUTHOR]

• A novel method for simultaneous determination of quinones in Rubia cordifolia L was developed. • Rubia cordifolia L. could improve fibrinolysis system by inhibiting HIF-1/PAI-1. • Rubia cordifolia L. could improve arachidonic acid metabolism by inhibiting COX-2 and cPLA2. • Mollugin played an important in role Rubia cordifolia L for treating abnormal uterine bleeding. The roots of Rubia cordifolia L. (RCL) have become an important medicine for abnormal uterine bleeding (AUB) and hemorrhage syndrome in Traditional Asian medicine. However, the underlying mechanism and the material basis of RCL for treating AUB has not been fully elucidated. In this study, quantitative evaluation of quinones, systematic pharmacology and experimental verification were adopted. Firstly, the Disease-Ingredient-Target network was established by Cytoscape, which was consistent with 23 compounds and 47 target genes. The hub targets were discovered by Maximal Clique Centrality (MCC) method with Cytohubba plugins of Cytoscape, and top 20 nodes were ranked by MCC. It was assumed that mollugin is the main ingredient of RCL for treating AUB. Pathways on which RCL acted were obtained from observation of its biological functions, KEGG pathways and Reactome pathway enrichment analysis. The possible mechanism of RCL for treating AUB was revealed for improvment of the blood clotting system, blood circulation, arachidonic acid metabolism and inflammation. Then, a novel method for evaluating the quality of RCL was established, and the content of mollugin in RCL was the higher than others. Finally, pharmacologic experiments confirmed that RCL could improve the inflammation by inhibiting the activity of COX-2 and cPLA 2 enzyme, ameliorate blood hypercoagulability by affecting coagulation cascade and fibrinolytic system. It was found that RCL inhibited the expression COX-2 and PAI-1 by reducing HIF-1α expression. The trend of each index of mollugin was consistent with that of RCL, indicating that it played an important role in RCL for treating AUB. The above results could provide a novel method for the quality evaluation of RCL and was expected to give us more important information regarding the use of RCL as a promising drug candidate for AUB, offering a fertility preserving medical, non-hormonal treatment choose for women with AUB. [ABSTRACT FROM AUTHOR]

Plumbagin (PL) pharmacologically plays the anti-proliferative effects in cancer cells, including effective suppression of colorectal cancer (CRC). However, the exact molecular mechanism of PL to treat CRC remains unclear. Using available SwissTargetPrediction and SuperPred databases, the anti-cancer biotargets of PL were identified, and the CRC-diseased targets were obtained through a DisGeNET database. The biological processes, and signaling pathways of PL to treat CRC were identified and visualized. Further, clinical and cell culture data were used to validate some bioinformatic findings. As shown in bioinformatics findings, 64 predictive biotargets of PL to treat CRC were collected, and 7 most important biotargets of tumor protein p53 (TP53), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), mitogen-activated protein kinase 1 (MAPK1), E1A-associated protein p300 (EP300), poly (ADP-ribose) polymerase 1 (PARP1), nuclear factor kappa p65 protein (RELA), Bcl-2 like protein 1 (BCL2L1) were identified respectively. In addition, top 20 functional biological processes, signaling pathways of PL to treat CRC were screened and prioritized. In human study, CRC samples showed elevated expressions of neoplastic MAPK1, PARP1 mRNAs and reduced EP300 mRNA level. In cell culture study, PL-treated CRC cells resulted in down-regulated MAPK1, PARP1 mRNA expressions and up-regulation of EP300 mRNA level, characterized with suppressed cell proliferation. Taken together, the therapeutic biotargets and molecular mechanisms of PL to treat CRC were screened and identified by using a systematic pharmacology analysis, and some bioinformatic findings were validated in clinical and cell line experiments. Potentially, these hub biotargets may be the biomarkers for CRC detection and treatment. Image 1 • All available biotargets of PL and CRC for constructing a PPI network of PL to treat CRC. • Identification of the important hub biotargets of PL to treat CRC. • Visualization of top 20 biological processes, signaling pathways of PL to treat CRC. • Some of hub biotargets were validated in human and cell culture studies. • These hub biotargets may be the potential biomarkers for screening CRC. [ABSTRACT FROM AUTHOR]

• Ephedra, Almond, Platycodon grandiflorum , Licorice and Scutellaria were identified as the five core drugs (HXF) in TCM mediated MPP treatment. • Total ninety-three active ingredients which are expected to be the effective components for MPP treatment were screened out. • TNF, β2AR and PTGS2 play pivotal role in TCM mediated MPP inhibition. • Three functional modules (suppression of inflammation, reduction of airway hyper-responsiveness and promotion of epithelial cell apoptosis) and five signaling pathways (C–type lectin receptors (CLRs), Pertussis, TNF, Th17 and IL17 signaling pathways) are key components in this complex bio-pathway network. Traditional Chinese Medicine (TCM) is widely used in the treatment of Mycoplasma pneumoniae Pneumonia (MPP) in East Asia. However, our current understanding of the underlying molecular mechanism remains dispersive and promiscuous. In this study, a systematic pharmacological approach combined with literature data mining was applied for drug similarity evaluation, drug half-life evaluation, oral bioavailability prediction, drug target exploration, Gene Ontology (GO) analysis, KEGG pathway enrichment and network construction, thus providing the rationale for its clinical performance. Five mostly studied herbs, including Ephedra Herba, Amygdalus communis Vas, Platycodon grandiforus , Licorice and Scutellariae Radix, were selected from the literature. Total ninety-three active ingredients, which are expected to be the effective components for MPP treatment, were screened out. Interrelationship between active compounds, drug targets and signaling pathways were analyzed to reveal the therapeutic effect of TCM in detail. Of importance, we found that TNF, β2AR and PTGS2 play pivotal role in TCM mediated MPP inhibition. And mechanistically, epithelial apoptosis (defensive barrier function), GPCR signaling (symptom amelioration) and immune pathways (innate signaling and adaptive Th17 response) are critically involved. Our work, achieved through systematic pharmacology and data mining, enlarges the knowledge of TCM in MPP therapy, and could provide valuable insights for further drug discovery studies. [ABSTRACT FROM AUTHOR]

Objective: To explore the mechanism of Radix Rhei Et Rhizome (Dahuang, DH) intervention in intracerebral hemorrhage (ICH) based on systematic pharmacology and proteomics strategy., Methods: The systematic pharmacological strategies were utilized to find the bioactive compounds of Radix Rhei Et Rhizome, predict its potential targets, and collect ICH's disease genes; then, the Cytoscape 3.7.1 software was applied for network construction and network topology analysis. After that, in-depth analysis of the proteomics data of Radix Rhei Et Rhizome intervention in ICH was performed to complement and validate the results of systematic pharmacological predictions., Results: A total of three major networks were constructed in the present study: (1) compound-compound target network of Radix Rhei Et Rhizome, (2) DH-ICH PPI network, (3) proteomics proteins' PPI network. These three major networks have been analyzed by network topology, and several small networks derived (such as signaling pathway networks). The enrichment analysis showed that Radix Rhei Et Rhizome can intervene in several biological process (such as inflammation, smooth muscle proliferation, platelet activation, blood pressure regulation, angiogenesis, hypoxia, and inflammatory response of leukocytes), signaling pathway (such as FoxO signaling pathway, complement and coagulation cascades, cGMP-PKG signaling pathway, and Rap1 signaling pathway), and reactome pathway (such as signaling by interleukins, interleukin-4 and interleukin-13 signaling, nuclear receptor transcription pathway, and platelet activation)., Conclusion: Radix Rhei Et Rhizome may intervene in ICH-related biological process, signaling pathway, and reactome pathway found in this research so as to achieve the effect of treating ICH related injuries., (© 2021 The Author(s).)

Background: Xuefu Zhuyu decoration (XFZYD), as a traditional Chinese compound recipe, has been used to treat atherosclerosis cardiovascular disease (ASCVD) for thousands of years in China, but its effective compounds and underlying treatment molecular mechanism remains promiscuous, which severely limits its clinical application. Methods: The effective components and their targets of XFZYD were predicted and screened based on the Traditional Chinese Medicine System Pharmacology (TCMSP) database. The candidate therapeutic targets of ASCVD were screened by Pharmacogenomics Knowledgebase (PharmGKB) and Comparative Toxicogenomics Database (CTD). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Differentially expressed genes were identified using the GEO2R online tool. Molecular docking was performed by Schrodinger software. To assess the efficacy of the prediction, human umbilical vein endothelial cells (HUVECs) treated with the effective compound of XFZYD were used as the in vitro model. Results: A total of 108 effective compounds (including quercetin) and 137 candidate therapeutic targets were identified. Analyzing the relationships among effective compounds, candidate therapeutic targets, and signaling pathways, the therapy mechanisms of XFZYD were mainly reflected in the protection of vascular endothelium, anti-inflammatory, antioxidant stress, etc. Accordingly, we found the effective compound of XFZYD (quercetin) decreased intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expressions and pro-inflammatory cytokines in HUVECs treated with lipopolysaccharide (LPS), and reduced the adhesion function of HUVECs with monocytes. The inhibitor of the predicted target protein (PTGS2) could further reduce the expressions of VCAM-1, ICAM-1, and TNF-α induced by LPS, and inhibit the adhesion function of HUVECs with monocytes, while PTGS2 agonists partially counteracted the protective effect of quercetin. Conclusions: In this study, the effective components and potential therapeutic targets of XFZYD for ASCVD treatment were explored from the perspective of systemic pharmacology. The effective component quercetin was verified to protect endothelial cells by reducing endothelial inflammatory response and impeding the attachment of monocytes against the predicted therapeutic target PTGS2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Liang, Xiang, Zhang, Wang, Jin, Zhao and Zheng.)

Objective: To explore the mechanism of Shengmai Yin (SMY) for coronary heart disease (CHD) by systemic pharmacology and chemoinformatics., Methods: Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), traditional Chinese medicine integrative database (TCMID) and the traditional Chinese medicine (TCM) Database@Taiwan were used to screen and predict the bioactive components of SMY. Pharmmapper were utilized to predict the potential targets of SMY, the TCMSP was utilized to obtain the known targets of SMY. The Genecards and OMIM database were utilized to collect CHD genes. Cytoscape was then used for network construction and analysis, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. After that, animal experiments were then performed to further validate the results of systemic pharmacology and chemoinformatics., Results: Three major networks were constructed: (1) CHD genes' protein-protein interaction (PPI) network; (2) SMY-CHD PPI network; (3) SMY known target-CHD PPI network. The other networks are minor networks generated by analyzing the three major networks. Experimental results showed that compared with the model group, the Shengmai injection (SMI) can reduce the myocardial injury score and the activities of serum aspartate aminoconvertase (AST), CK and lactate dehydrogenase (LDH) in rats (P<0.05), and reduce serum lipid peroxide (LPO) content and increase serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in myocardial infarction rats (P<0.05). SMI can also decrease the expression of MMP-9 mRNA and increase that of TIMP-1 mRNA (P<0.01)., Conclusion: SMY may regulate the signaling pathways (such as PPAR, FoxO, VEGF signaling), biological processes (such as angiogenesis, blood pressure formation, inflammatory response) and targets (such as AKT1, EGFR, MAPK1) so as to play a therapeutic role in CHD., (© 2020 The Author(s).)