Exploring the mechanism of action of Shuangyang houbitong granules in the treatment of acute pharyngitis based on network pharmacology and molecular docking.

BACKGROUND: Acute pharyngitis (AP) refers to the acute inflammation of the pharynx, characterized by swelling and pain in the throat. Shuangyang houbitong granules (SHG), a traditional Chinese medicine compound, have been found to be effective in providing relief from symptoms associated with AP. METHODS: The chemical components of SHG were screened using Traditional Chinese Medicine Systems Pharmacology database, HERB database, and China National Knowledge Infrastructure. The targets of the granules were predicted using SwissTargetPrediction database. A network was constructed based on the targets of AP obtained from Genecards database, and protein-protein interaction analysis was performed on the intersection targets using STRING database. Key targets were screened for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and the binding activity of components and targets was predicted using AutoDockTools-1.5.7. RESULTS: A total of 65 components of SHG that met the screening criteria were retrieved, resulting in 867 corresponding targets. Additionally, 1086 AP target genes were retrieved, and 272 gene targets were obtained from the intersection as potential targets for SHG in the treatment of AP. Molecular docking results showed that the core components genkwanin, acacetin, apigenin, quercetin can stably bind to the core targets glyceraldehyde 3-phosphate dehydrogenase, interleukin 6, tumor necrosis factor, serine/threonine protein kinase, tumor protein 53, and epidermal growth factor receptor. CONCLUSION: The research results preliminarily predict and verify the mechanism of action of SHG in the treatment of AP, providing insights for further in-depth research.

The efficacy and safety of diterpene ginkgolides meglumine injection for cerebral infarction: A meta-analysis of randomized controlled trials.

OBJECTIVE: To systemically evaluate the efficacy and safety of diterpene ginkgolides meglumine injection (DGMI) on cerebral infarction (CI). METHODS: Comprehensively collect randomized controlled trials of DGMI in the treatment of CI in 7 databases including Embase, PubMed, the Cochrane Library, the China National Knowledge Infrastructure Database, the WanFang Database, the China Science and Technology Journal Database, and the China Biology Medicinedisc as of January 2023. The studies were screened according to the inclusion and exclusion criteria and evaluated according to the criteria recommended by the Cochrane Handbook, then RevMan 5.3, Stata 12.0 software were used for Meta-analysis. RESULTS: A total of 22 randomized controlled trials with 2194 patients were included. Meta analysis showed that: the total effective rate of treatment (relative risk = 1.29, 95% confidence interval (1.21, 1.38), P < .001), National Institute of Health stroke scale score, Barthel index and Modified Rankin Scale were better in DGMI group than in Conventional Western Medicine Treatment group. The included studies reported 42 adverse events, 25 of which belonged to DGMI groups. CONCLUSION: Available evidence suggested that DGMI can significantly improve the clinical efficiency in the treatment of CI. DGMI is an ideal treatment for CI, which has high clinical application value.

Systematic review and meta-analysis on the efficacy and safety of Injectable Lentinan combined with chemotherapy in the treatment of gastric cancer.

BACKGROUND: This study employed a meta-analysis to evaluate the efficacy and safety of adjunctive treatment with injectable Lentinan (LNT) in combination with chemotherapy for gastric cancer (GC). METHODS: Computer-based searches of 6 databases were performed to identify randomized controlled trials (RCTs) relevant to the treatment of GC with LNT through mid-March 2023. Two independent researchers performed risk of bias assessment and trial sequential analysis(TSA), extracted the data and used Revman 5.3 software for data analysis. The certainty of evidence was graded based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: A total of 31 RCTs with 2729 patients were included in the analysis. The results revealed that adjunctive therapy with LNT was associated with improved treatment efficacy (RR = 1.48, 95%CI: 1.36 ∼ 1.61, p < 0.00001), improvement in clusters of differentiation (CD3+, CD4+, and CD4+/CD8+), natural killer (NK) cells, and quality of life assessment (RR = 1.32, 95%CI: 1.20 ∼ 1.45, p < 0.00001) compared to using chemotherapy alone. In addition, there was a reduction in CD8+ levels, incidence of white blood cell decline, gastrointestinal reactions, and platelet decline. TSA results indicated that there was sufficient evidence to draw firm conclusions about these outcomes, and the GRADE scores showed 'high' or 'moderate' quality of evidence for these outcomes. CONCLUSION: The efficacy of treatment of GC with LNT in combination with chemotherapy was found to be better than chemotherapy alone. And no serious adverse effects were observed. However, further RCTs are needed to further validate the results of this study.

Isoliquiritigenin inhibits virus replication and virus-mediated inflammation via NRF2 signaling.

BACKGROUND: The transcription factor NRF2 is a master redox switch that regulates the cellular antioxidant response. However, recent advances have revealed new roles for NRF2, including the regulation of antiviral responses to various viruses, suggesting that pharmacological NRF2-activating agents may be a promising therapeutic drug for viral diseases. Isoliquiritigenin (ISL), a chalcone isolated from liquorice (Glycyrrhizae Radix) root, is reported to be a natural NRF2 agonist and has has antiviral activities against HCV (hepatitis C virus) and IAV (influenza A virus). However, the spectrum of antiviral activity and associated mechanism of ISL against other viruses are not well defined. PURPOSE: This study investigated the antiviral activity and underlying mechanism of ISL against vesicular stomatitis virus (VSV), influenza A virus (H1N1), encephalomyocarditis virus (EMCV), herpes simplex virus type 1 (HSV-1). METHODS: We evaluated the antiviral activity of ISL against VSV, H1N1, EMCV, and HSV-1 using flow cytometry and qRT-PCR analysis. RNA sequencing and bioinformatic analysis were performed to investigate the potential antiviral mechanism of ISL. NRF2 knockout cells were used to investigate whether NRF2 is required for the antiviral activity of ISL. The anti-apoptosis and anti-inflammatory activities of ISL were further measured by counting cell death ratio and assessing proinflammatory cytokines expression in virus-infected cells, respectively. In addition, we evaluated the antiviral effect of ISL in vivo by measuring the survival rate, body weights, histological analysis, viral load, and cytokine expression in VSV-infected mouse model. RESULTS: Our data demonstrated that ISL effectively suppressed VSV, H1N1, HSV-1, and EMCV replication in vitro. The antiviral activity of ISL could be partially impaired in NRF2-deficient cells. Virus-induced cell death and proinflammatory cytokines were repressed by ISL. Finally, we showed that ISL treatment protected mice against VSV infection by reducing viral titers and suppressing the expression of inflammatory cytokines in vivo. CONCLUSION: These findings suggest that ISL has antiviral and anti-inflammatory effects in virus infections, which are associated with its ability to activate NRF2 signaling, thus indicating that ISL has the potential to serve as an NRF2 agonist in the treatment of viral diseases.

Identification of key pharmacological components and targets for Aidi injection in the treatment of pancreatic cancer by UPLC-MS, network pharmacology, and in vivo experiments.

BACKGROUND: Pancreatic cancer is one of the most lethal cancers worldwide. Aidi injection (ADI) is a representative antitumor medication based on Chinese herbal injection, but its antitumor mechanisms are still poorly understood. MATERIALS AND METHODS: In this work, the subcutaneous xenograft model of human pancreatic cancer cell line Panc-1 was established in nude mice to investigate the anticancer effect of ADI in vivo. We then determined the components of ADI using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) and explored the possible molecular mechanisms against pancreatic cancer using network pharmacology. RESULTS: In vivo experiments, the volume, weight, and degree of histological abnormalities of implanted tumors were significantly lower in the medium and high concentration ADI injection groups than in the control group. Network pharmacology analysis identified four active components of ADI and seven key targets, TNF, VEGFA, HSP90AA1, MAPK14, CASP3, P53 and JUN. Molecular docking also revealed high affinity between the active components and the target proteins, including Astragaloside IV to P53 and VEGFA, Ginsenoside Rb1 to CASP3 and Formononetin to JUN. CONCLUSION: ADI could reduce the growth rate of tumor tissue and alleviate the structural abnormalities in tumor tissue. ADI is predicted to act on VEGFA, P53, CASP3, and JUN in ADI-mediated treatment of pancreatic cancer.

A novel strategy to reveal clinical advantages and molecular mechanism of aidi injection in the treatment of pancreatic cancer based on network meta-analysis and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pancreatic cancer is a common malignancy worldwide due to its poor prognosis and high mortality rate. It is clinically proven that the combination of chemotherapeutic drugs and Traditional Chinese Medicine injections (TCMIs) significantly improves the therapeutic effect. AIM OF THE STUDY: To evaluate the efficacy and clinical benefits of TCMIs in combination with chemotherapy in the treatment of pancreatic cancer and to explore the mechanism of clinical advantage of Aidi injection. METHODS: Randomized controlled trials (RCTs) were searched in databases by NMA before December 29, 2020. WinBUGS 1.4, Stata 14.0, and R 4.0.4 software were used for calculations. All results were expressed as odds ratios and 95% credible intervals. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed. And then, biological experiments were integrated to verify the results of network pharmacology analysis. (PROSPERO ID: CRD42021283559). RESULTS: A total of 33 RCTs with 8 TCMIs and 2011 patients were included. The results of NMA showed that Aidi injection can significantly improve the clinical efficacy (OR = 0.34, 95%CI: 0.16-0.74), and the clinical advantage was that it can significantly alleviate the leukopenia and thrombocytopenia caused by chemotherapy (OR = 5.65, 95%CI: 1.18-28.13). A total of 23 chemical compounds and 280 potential targets for Aidi injection were obtained from the online databases. Among them, there were 22 compounds, 50 targets and 211 signaling pathways closely related to leukopenia. Five genes were predicted to be core targets of ADI in alleviating leukopenia, and 2 of them (TP53 and VEGFA) were confirmed by biological experiments as regulatory targets of ADI in the treatment of PC. CONCLUSIONS: In conclusion, TCMIs in combination with chemotherapy, can improve clinical efficacy and safety in the treatment of pancreatic cancer. However, the overall evidence base is low, and large samples with multi-center RCTs are still needed to support further research findings. Aidi injection can alleviate leukopenia mainly by intervening in oxidative stress, regulating cell proliferation and apoptosis, and regulating the inflammatory response. The combined application of NMA, network pharmacology, and biological experiments provides a reference for clinical evaluation and mechanism of action exploration of other drugs.

Exploring potential mechanisms of Suhexiang Pill against COVID-19 based on network pharmacology and molecular docking.

BACKGROUND: The traditional Chinese medicine prescription Suhexiang Pill (SHXP), a classic prescription for the treatment of plague, has been recommended in the 2019 Guideline for coronavirus disease 2019 (COVID-19) diagnosis and treatment of a severe type of COVID-19. However, the bioactive compounds and underlying mechanisms of SHXP for COVID-19 prevention and treatment have not yet been elucidated. This study investigates the mechanisms of SHXP in the treatment of COVID-19 based on network pharmacology and molecular docking. METHODS: First, the bioactive ingredients and corresponding target genes of the SHXP were screened from the traditional Chinese medicine systems pharmacology database and analysis platform database. Then, we compiled COVID-19 disease targets from the GeneCards gene database and literature search. Subsequently, we constructed the core compound-target network, the protein-protein interaction network of the intersection of compound targets and disease targets, the drug-core compound-hub gene-pathway network, module analysis, and hub gene search by the Cytoscape software. The Metascape database and R language software were applied to analyze gene ontology biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, AutoDock software was used for molecular docking of hub genes and core compounds. RESULTS: A total of 326 compounds, 2450 target genes of SHXP, and 251 genes related to COVID-19 were collected, among which there were 6 hub genes of SHXP associated with the treatment of COVID-19, namely interleukin 6, interleukin 10, vascular endothelial growth factor A, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), and epidermal growth factor. Functional enrichment analysis suggested that the effect of SHXP against COVID-19 is mediated by synergistic regulation of several biological signaling pathways, including Janus kinase/ STAT3, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), T cell receptor, TNF, Nuclear factor kappa-B, Toll-like receptor, interleukin 17, Chemokine, and hypoxia-inducible factor 1 signaling pathways. SHXP may play a vital role in the treatment of COVID-19 by suppressing the inflammatory storm, regulating immune function, and resisting viral invasion. Furthermore, the molecular docking results showed an excellent binding affinity between the core compounds and the hub genes. CONCLUSION: This study preliminarily predicted the potential therapeutic targets, signaling pathways, and molecular mechanisms of SHXP in the treatment of severe COVID-19, which include the moderate immune system, relieves the "cytokine storm," and anti-viral entry into cells.

Investigation on the mechanisms of guiqi huoxue capsule for treating cervical spondylosis based on network pharmacology and molecular docking.

BACKGROUND: Guiqi huoxue capsule (GQHXC) is a patented Chinese medicine used for treating a liver and kidney deficiency and blood stasis syndrome due to qi deficiency. It is caused by cervical spondylosis (cervical spondylotic radiculopathy (CSR), mixed cervical spondylosis mainly composed of nerve root type). Its underlying mechanisms need, however, to be further clarified. METHODS: In this study, collecting compounds, predicting therapeutic targets, constructing networks, and analyzing biological functions and pathways were based on network pharmacology analysis. In addition, molecular docking verification was engaged to assess the binding potential of selected target-compound pairs. RESULTS: We established 5 networks: compound-putative target network of GQHXC, protein-protein interaction (PPI) network related to CSR, compound-CSR target network, potential therapeutic targets PPI network, and herb-compound-target-pathway network. Network analysis indicated that 7 targets (tumor necrosis factor [TNF], interleukin 6 [IL6], nitric oxide synthase 3 [NOS3], Interleukin-8 [CXCL8], prostaglandin-endoperoxide synthase 2 [PTGS2], vascular endothelial growth factor A [VEGFA], and AP-1 transcription factor subunit [JUN]) might be the therapeutic targets of GQHXC in CSR. Moreover, molecular docking verification showed that TNF, IL6, NOS3, CXCL8, PTGS2, VEGFA, and JUN had a good is interaction with the corresponding compounds. Furthermore, enrichment analysis indicated that GQHXC might exert a curative role in CSR by regulating some important pathways, such as TNF signaling pathway, NF-kappa B signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and so on. CONCLUSION: Our study preliminarily explained the underlying mechanisms of GQHXC for treating CSR, and molecular docking verification was adopted as an additional verification. These findings laid a valuable foundation for experimental research and further application of GQHXC in the clinical treatment of CSR.

A Multidimensional Bayesian Network Meta-Analysis of Chinese Herbal Injections for Treating Non-small Cell Lung Cancer With Gemcitabine and Cisplatin.

Introduction: As non-small cell lung cancer (NSCLC) seriously threatens human health, several clinical studies have reported that Chinese herbal injections (CHIs) in combination with and gemcitabine plus cisplatin (GP) are beneficial. This multidimensional network meta-analysis aimed to compare the clinical efficacy and safety of different CHIs in combination with GP against NSCLC. Methods: Randomized controlled trials (RCTs) for the treatment of NSCLC were retrieved from seven electronic databases from inception to April 30, 2020. Study selection and data extraction were based on a priori criteria. Data analysis was performed using Stata 13.0, WinBUGS 14.0 software. Multidimensional cluster analysis was performed using the "scatterplot3d" package in R 3.6.1 software. Results: This network meta-analysis included 71 eligible RCTs and 10 Chinese herbal injections. Delisheng injection and Kangai injection had the highest probability in terms of clinical effectiveness rate (94.60%) and gastrointestinal reactions (82.62%) when combined with GP compared with the other interventions. Compound Kushen injection combined with GP ranked ahead of the other interventions in terms of performance status (73.36%) and abnormal liver function (87.17%). Shenmai injection combined with GP had the highest probability in terms of leukopenia (94.59%) and thrombocytopenia (99.18%). Conclusion: The current evidence revealed that CHIs combined with GP have a better impact on patients with NSCLC than GP alone. Aidi injection, Compound kushen injection, and Kanglaite injection deserve more attention of clinicians when combined with GP in patients with NSCLC. Additionally, due to the limitations of this network meta-analysis, further well-designed, large-sample, multicenter RCTs are required to support our findings adequately.

Investigation on the clinical efficacy and mechanism of compound kushen injection in treating esophageal cancer based on multi-dimensional network meta-analysis and in vitro experiment.

ETHNOPHARMACOLOGICAL RELEVANCE: Esophageal cancer, as a high incidence of gastrointestinal cancer, has an indelible impact on human life and health. The combination of Chinese herbal injections and chemotherapy is commonly applied in the treatment of Esophageal cancer. AIM OF THE STUDY: This study aimed to confirm the clinical advantage of Compound Kushen Injection to treat esophageal cancer and explore its molecular mechanism. METHODS: The network meta-analysis method was used for the clinical evaluation of anti-tumor Chinese herbal injections. Initially, several electronic databases were searched to identify randomized controlled trials regarding Chinese herbal injections to treat esophageal cancer from their inception to September 5, 2020. Then, WinBugs and Stata software was used to calculate and analyze the outcome indicators, including total clinical efficiency, improvement of quality of life and adverse reactions. Furthermore, the surface under the cumulative ranking curve and three-dimensional cluster analysis were used to rank the efficacy and safety of Chinese herbal injections about each outcome. Cell Counting Kit-8 assay was used to observe the effect of Compound Kushen Injection on the proliferation of esophageal cancer cells. Real-Time Quantitative PCR and Western Blot analysis were used to detect the mRNA and protein expression of EGFR and AURKA in ESCA cells. RESULTS: The surface under the cumulative ranking curve of Compound Kushen Injection combined with chemotherapy in total clinical efficiency, quality of life, reduction of nausea and vomiting were ranking at 89.1%, 81.8% and 92.4%, respectively. Compound Kushen Injection was determined as the dominant variety in the treatment of esophageal cancer which can inhibit the proliferation of esophageal cancer cells and downregulate the overexpression of EGFR and AURKA mRNA and protein. CONCLUSION: In this study, network meta-analysis was applied to confirm that Compound Kushen Injection has a curative effect on esophageal cancer and is superior to other anti-tumor Chinese herbal injections. Combined with the network pharmacology and in vitro experiment, the mechanism of Compound Kushen Injection inhibiting the proliferation of esophageal cancer cells by regulating the abnormal expression of EGFR and AURKA was revealed.

Investigation on the Efficiency of Chinese Herbal Injections combined with Concurrent Chemoradiotherapy for Treating Nasopharyngeal Carcinoma based on Multidimensional Bayesian Network Meta-analysis.

Introduction: Given the wide utilization of Chinese herbal injections in the treatment of nasopharyngeal carcinoma (NPC), this network meta-analysis (NMA) was devised to compare the clinical efficacy and safety of different Chinese herbal injections combined with concurrent chemoradiotherapy (CCRT) against NPC. Methods: Randomized controlled trials (RCTs) were retrieved from seven electronic databases from the date of database establishment to October 5, 2020. Study selection and data extraction conformed to a priori criteria. Focusing on clinical effective rate, performance status, grade ≥3 oral mucositis, nausea and vomiting, leukopenia, and thrombopenia, this NMA was performed with Review Manager 5.3.5, Stata 13.1, WinBUGS 1.4.3, and R 4.0.3 software. Results: Ten inventions from 37 RCTs involving 2,581 participants with NPC that evaluated the clinical effective rate, nausea and vomiting, leukopenia, thrombopenia, and grade ≥3 oral mucositis were included. Compared with CCRT alone, Elemene injection and Compound Kushen injection were associated with significantly improved clinical effective rates, and Elemene injection plus CCRT had the highest probability in terms of clinical effective rate (78.07%) compared with the other interventions. Shenqifuzheng injection, Xiaoaiping injection, and Shenmai injection ranked the best in terms of performance status (79.02%), nausea and vomiting (86.35%), and grade ≥3 oral mucositis (78.14%) when combined with CCRT. Kangai injection combined with CCRT ranked ahead of the other injections in terms of leukopenia (90.80%) and thrombopenia (91.04%), and had a better impact on improving performance status and reducing leukopenia, thrombopenia, grade ≥3 oral mucositis, and nausea and vomiting in the multidimensional cluster analysis. Conclusion: Current clinical evidence indicates that Elemene injection combined with CCRT has the best clinical effective rate and that Kangai injection might have a comprehensively better impact on improving performance status and reducing adverse reactions against NPC. Additionally, due to the limitations of this NMA, more multicenter, high-quality, and head-to-head RCTs are needed to properly support our findings.

Investigation on the Efficiency of Tonic Chinese Herbal Injections for Treating Dilated Cardiomyopathy Based on Bayesian Network Meta-Analysis.

INTRODUCTION: This network meta-analysis investigated the efficacy of six tonic Chinese herbal injections (Huangqi injection, Shenfu injection, Shengmai injection, Shenmai injection, Shenqi Fuzheng injection, and Yiqifumai injection) compared to Western medicine for the treatment of the deteriorating state associated with dilated cardiomyopathy. METHODS: PubMed, the Cochrane Library, Embase, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, the Wanfang Database, and the Chinese Scientific Journal Database were searched from their inception to October 15, 2020, to retrieve randomized controlled trials (RCTs). Study selection and data extraction conformed to a priori criteria. The risk of bias of the included RCTs was determined, and GRADE was used to evaluate outcomes. The network meta-analysis was calculated using WinBUGS 1.4.3 and Stata 13.0 software. The clinical effective rate, left ventricular ejection fraction, 6-minute walk test, left ventricular end-diastolic dimension, heart rate, and cardiac output were deemed outcomes. All outcomes were summarized as odds ratios or mean differences with their 95% credible intervals. The ranking probability of the interventions across various outcomes was also presented. RESULTS: Forty RCTs and 2970 patients were enrolled. Integration of the outcome results revealed that a combination of Shenfu injection and Western medicine ranked ahead of the other injections in most outcomes, especially in the clinical effective rate (OR = 0.21, 95% CI: 0.12-0.34), left ventricular ejection fraction (MD = 7.43, 95% CI: 2.41-12.38), and 6-minute walk test (MD = 50.39, 95% CI: 25.78-76.33). Shenmai injection plus Western medicine ranked ahead of the other injections in left ventricular end-diastolic dimension (69.5%) and cardiac output (60.9%). The cluster analysis suggested that Shenfu injection plus Western medicine was the most effective intervention for dilated cardiomyopathy. CONCLUSIONS: Shenfu injection plus Western medicine may be a preferable treatment in dilated cardiomyopathy. Clinicians should also consider the specific patient's various conditions when making diagnostic decisions. Due to an insufficient network meta-analysis, more high-quality RCTs need to be implemented to support our conclusions.

Comparative Efficacy of Chinese Herbal Injections Combined with Paclitaxel Plus Cisplatin for Non-Small-Cell Lung Cancer: A Multidimensional Bayesian Network Meta-Analysis.

INTRODUCTION: Considering the limitations of pure paclitaxel plus cisplatin chemotherapy in the treatment of non-small-cell lung cancer and the extensive exploration of Chinese herbal injections, this study performed a multidimensional network meta-analysis to systematically evaluate the clinical efficacy and safety of 12 Chinese herbal injections in the treatment of non-small-cell lung cancer. METHODS: Randomized controlled trials were obtained from several databases according to the eligibility criteria, and the study quality was assessed by the Cochrane risk of bias tool. Data analysis was performed by Stata 13.1 software and WinBUGS 14.0 software. Multidimensional cluster analysis was performed with the "scatterplot3d" package in R 3.6.1 software (PROSPERO ID: CRD42020163503). RESULTS: A total of 58 eligible randomized controlled trials involving 4578 patients and 12 Chinese herbal injections were included. Combined with paclitaxel plus cisplatin chemotherapy, Xiaoaiping injection exhibited a better impact on the clinical effective rate than paclitaxel plus cisplatin alone. Shenqifuzheng injection was associated with a preferable response in performance status and reduced leukopenia and gastrointestinal reactions. Kangai injection was dominant in the comprehensive results of the cluster analysis. CONCLUSIONS: Chinese herbal injections combined with paclitaxel plus cisplatin chemotherapy have a certain adjuvant effect in treating non-small-cell lung cancer, but the results of this study need to be verified by more well-designed, large-sample, multicenter randomized controlled trials.

Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking.

BACKGROUND: Yuzhi Zhixue Granule (YZG) is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG. METHODS: The active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein-protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules. RESULTS: The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds. CONCLUSION: This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.

Comparative Efficacy of Chinese Herbal Injections for the Treatment of Herpangina: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Considering the limitations of broad-spectrum antiviral drugs for the treatment of herpangina and the extensive exploration of Chinese herbal injections (CHIs), systematic evaluation of the efficacy of different CHIs in the treatment of herpangina is a key imperative. In this study, we performed a network meta-analysis to investigate the efficacy of CHIs, including Reduning injection (RDN), Shuanghuanglian injection (SHL), Tanreqing injection (TRQ), Xiyanping injection (XYP), and Yanhuning injection (YHN), in the treatment of herpangina. METHODS: A systematic literature review including studies published before December 17, 2018, was conducted in several databases. The quality of the included studies was assessed using the Cochrane risk of bias tool. Data were analyzed using STATA 13.0 and WinBUGS 1.4.3 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Clustering analysis was performed to compare the effects of CHIs between two different outcomes. RESULTS: A total of 72 eligible randomized controlled trials involving 8,592 patients and five CHIs were included. All patients were under the age of 15 years, and most were under 7 years. The results of the network meta-analysis showed that RDN, XYP, and YHN had significantly better treatment performance than ribavirin. SHL (OR: 0.18; 95% CI: 0.09-0.34) and TRQ (OR: 0.18; 95% CI: 0.10-0.31) were obviously superior to ribavirin with respect to total clinical effectiveness. The results of SUCRA and cluster analysis indicated that RDN is the best intervention with respect to total clinical effectiveness, antipyretic time, and blebs disappearing time. Fifty-four studies described adverse drug reactions/adverse drug events (ADRs/ADEs), and 32 studies reported ADRs/ADEs in detail. CONCLUSIONS: CHIs were found to be superior to ribavirin in terms of treatment performance and may be beneficial for patients with herpangina. RDN had the potential to be the best CHI with respect to all outcome measures. More evidence is needed to assess the safety aspects of CHIs.

Comparative Efficacy of Chinese Herbal Injections for Treating Pediatric Bronchopneumonia: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Pediatric bronchopneumonia is one of the common respiratory diseases in pediatrics. Chinese herbal injections (CHIs) are widely used to treat pediatric bronchopneumonia. In this study, we examined the efficacy of CHIs in the treatment of pediatric bronchopneumonia using a network meta-analysis (NMA). METHODS: Randomized controlled trials (RCTs) of CHIs combined western medicine (WM) versus WM were searched from electronic databases. WinBUGS 1.4.3 and Stata 13.0 were adopted to compute calculations and prepare graphs, respectively. RESULTS: 168 RCTs with 21917 patients were included. The results revealed that Xixinnao injection (XXN) + WM had the most probability to be the best intervention in the four aspects of rate of clinical efficacy, antipyretic time, cough disappearance time, and lung shadow disappearance time. While as to lung shadow disappearance time, asthma disappearance time, and hospitalization time, Yanhuning injection (YHN) + WM could be the best intervention. The safety of CHIs needs to be further assessed. CONCLUSIONS: Based on this NMA, XXN + WM and YHN + WM were potential optimal therapies in pediatric bronchopneumonia, and their safety should be strictly monitored.

A bioinformatics investigation into the pharmacological mechanisms of javanica oil emulsion injection in non-small cell lung cancer based on network pharmacology methodologies.

BACKGROUND: Javanica oil emulsion injection (JOEI) is an effective therapeutic option for patients with non-small cell lung cancer (NSCLC), but its mechanisms have not been fully elucidated. METHODS: In this study, we utilized network pharmacology to systematically investigate the bioactive components and targets of JOEI, identify common targets in NSCLC, and understand and evaluate the underlying mechanism of JOEI in the treatment of NSCLC through expression level, correlation, enrichment, Cox, survival and molecular docking analyses. The results indicated that five compounds of JOEI interact with five pivotal targets (LDLR, FABP4, ABCB1, PTGS2, and SDC4) that might be strongly correlated with the JOEI-mediated treatment of NSCLC. RESULTS: The expression level analysis demonstrated that NSCLC tissues exhibit low expression of FABP4, ABCB1, LDLR and PTGS2 and high SDC4 expression. According to the correlation analysis, a decrease in FABP4 expression was strongly correlated with decreases in LDLR and ABCB1, and a decrease in LDLR was strongly correlated with decreased PTGS2 and increased in SDC4 expression. Cox and survival analyses showed that the survival rate of the high-risk group was significantly lower than that of the low-risk group (p = 0.00388). In the survival analysis, the area under the curve (AUC) showed that the pivotal gene model exhibited the best predictive capacity over 4 years (AUC = 0.613). Moreover, the molecular docking analysis indicated that LDLR, FABP4, ABCB1, PTGS2 and SDC4 exhibit good binding activity with the corresponding compounds. CONCLUSION: In conclusion, this study predicted and verified that the mechanism of JOEI against NSCLC involves multiple targets and signaling pathways. Furthermore, this study provides candidate targets for the treatment of NSCLC, lays a good foundation for further experimental research and promotes the reasonable application of JOEI in clinical treatment.

Comparative Efficacy of Chinese Herbal Injections for Pulmonary Heart Disease: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Given the severity of pulmonary heart disease and the wide utilization of Chinese herbal injections, this network meta-analysis was devised to assess the comparative efficacy of seven Chinese herbal injections (Ciwujia injection, Dazhuhongjingtan injection, Huangqi injection, Shenfu injection, Shengmai injection, Shenmai injection, and Shenqi Fuzheng injection) that were combined with Western medicines in the treatment of pulmonary heart disease. METHODS: A literature search was performed in PubMed, Cochrane Library, EMBASE, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang Database, and the Chinese Scientific Journal Database from their inception to July14, 2019. This network meta-analysis was conducted in accordance with a priori eligibility criteria and methodological quality recommendations. Data analysis was performed with WinBUGS 1.4.3 and Stata 13.0 software focusing on clinical effectiveness rate, arterial blood gas analysis, hemorheology and hemodynamic indexes and right ventricular dimensions. In addition to the odds ratio or mean difference in various outcomes, the ranking probability of interventions calculated by the surface under the cumulative ranking area curve was demonstrated. The surface under the cumulative ranking area was equal to the rank of the intervention and was aimed to assess the best intervention. RESULTS: Ultimately, 118 randomized controlled trials including 10,085 patients were included. Integrating the outcome results, all eligible Chinese herbal injections plus Western medicines were superior to Western medicines alone, especially Shenfu injection+ Western medicines, Shenmai injection+ Western medicines, and Shenqi Fuzheng injection+ Western medicines. Regarding safety, the drip rate was an essential element for clinicians to consider during treatment. CONCLUSIONS: In conclusion, Shenfu injection+ Western medicines, Shenmai injection+ Western medicines and Shenqi Fuzheng injection+ Western medicines may be potential optimal treatments for pulmonary heart disease. A larger sample size and high-quality randomized controlled trials are needed to confirm and support this network meta-analysis.

Comparative Efficacy and Safety of Chinese Herbal Injections Combined With Cyclophosphamide and 5-Fluorouracil Chemotherapies in Treatment of Breast Cancer: A Bayesian Network Meta-Analysis.

Background: Given the limitations of chemotherapy for the treatment of breast cancer (BC) and the wide exploration of Chinese herbal injections (CHIs), this network meta-analysis (NMA) was conducted to analyze the comparative efficacy and safety of nine CHIs combined with CF (Cyclophosphamide and 5-Fluorouracil) chemotherapy regimens in the treatment of BC. Methods: Several electronic databases were searched to identify randomized controlled trials (RCTs) from inception to January 6, 2020. RCTs were screened by pre-established eligibility criteria, and the quality of which was assessed using the Cochrane risk of bias tool. Outcomes such as the clinical effectiveness rate, performance status, peripheral hemogram, and detection of T-lymphocyte subsets were analyzed using the Winbugs 1.4.3 and Stata 13.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Cluster analysis was performed to compare the effect of CHIs between two or three different outcomes. Results: A total of 84 RCTs involving 7855 patients and nine CHIs were included. The results showed that compared to CF chemotherapy regimens alone, the ones injected along with Aidi, Shenmai, Shenqi Fuzheng, Kangai, Kanglaite, or Shengmai combined with CF can improve the clinical effectiveness rate. Aidi, Shenmai, Shenqi Fuzheng, Compound Kushen, Kangai, and Kanglaite injection combined with CF can improve the performance status. Shenqi Fuzheng injection was considered as a favorable choice for relieving adverse reactions. According to the results of cluster analysis, Aidi injection and Compound Kushen injection plus CF were more favorable for the clinical effectiveness rate and performance status. Conclusion: In conclusion, Shenqi Fuzheng, Compound Kushen, Aidi, and Kangai injection combined with CF chemotherapy regimen have more significant effects for patients with BC. However, more high-quality clinical RCTs, especialy which correctly use blinding and allocation concealment, are required to support the conclusions.