The effects of Olmesartan/amlodipine administered in the Morning or At Night on nocturnal blood pressure reduction in Chinese patients with mild-moderate essential hypertension (OMAN Trial): study protocol for a prospective, multicenter, randomized, open-label clinical trial {1}.

INTRODUCTION: Hypertension increases the risk of cardiovascular disease. Uncontrolled nocturnal blood pressure is prevalent in patients taking antihypertensive medication, with an incidence rate of 30-60%. Although chronotherapy with antihypertensive agents may provide a new direction for effective control of nocturnal blood pressure, the clinical evidence base remains controversial. This research is presently underway to compare the effects of morning and bedtime administration of antihypertensive medication on nocturnal reduction and circadian rhythm of blood pressure in patients with hypertension. METHODS AND ANALYSIS: This study is being performed as a randomized, multicenter, open-label, parallel-group, clinical trial in which 720 participants are to undergo 24-h ambulatory blood pressure measurement (ABPM) and office blood pressure measurement (OBPM) at baseline before being randomly assigned to a morning (6-10 am) or a bedtime (6-10 pm) administration group. Each participant receives one 20/5-mg tablet of olmesartan/amlodipine (OA) daily for 4 weeks and is then followed up at 4-week intervals for a total of 12 weeks. During follow-up, the OA dosage is adjusted according to the ABPM and OBPM results. Patients with uncontrolled hypertension at the first follow-up visit will receive an increase in OA dosage to 1.5 tablets/day. For patients with blood pressure that is still uncontrolled after a further 4 weeks, the dosage of OA can be increased to 2 tablets/day. The primary objective is the reduction in mean nocturnal systolic blood pressure between baseline and week 12. The secondary objectives are the reduction in ambulatory blood pressure at weeks 4 and 12 and the blood pressure control rate at weeks 4, 8, and 12. DISCUSSION: Antihypertensive chronotherapy remains controversial. A superiority test hypothesis design has been adopted for this trial, in which all participants will be taking the same antihypertensive medication. We anticipate that our findings will determine if nocturnal blood pressure control in Chinese patients with essential hypertension varies according to whether antihypertensive medication is taken in the morning or at bedtime. This study may provide scientific evidence for the application of chronotherapy in clinical practice. TRIAL REGISTRATION: ChiCTR2200059719. Registered on 10 May 2022 ( http://www.chictr.org.cn/edit.aspx?pid=169782&htm=4 ) {2a,2b}.

Association between dietary approaches to stop hypertension (DASH) diet and hyperuricemia among Chinese adults: findings from a nationwide representative study.

BACKGROUND: Certain foods and food groups could positively or negatively impact serum uric acid (SUA) levels. However, evidence on the holistic dietary strategy to prevent and control hyperuricemia (HUA) development remains limited. OBJECTIVE: The aim of this research work was to explore the association of dietary approaches to stop hypertension (DASH) diet with SUA levels and odds of HUA among Chinese adults. METHODS: This research premise included 66,427 Chinese adults aged 18 and above who were part of the China Adult Chronic Disease and Nutrition Surveillance in 2015. Dietary consumptions were assessed via the household condiment weighing approach and a three-day, 24-hour dietary recall. Total fat, saturated fat, calcium, protein, potassium, cholesterol, magnesium, fiber, and sodium were all adopted to calculate the DASH score (score range, 0-9). The associations of DASH score with SUA levels and odds of HUA were evaluated using multiple linear and logistic regression models, respectively. RESULTS: We established that a higher DASH score was linked with a lower SUA levels (ß = - 0.11; 95% CI: - 0.12, - 0.1; p < 0.001) and odds of HUA (OR = 0.85; 95% CI: 0.83, 0.87; p < 0.001) after adjustment for age, sex, ethnicity, education status, marital status, health behaviours and health factors. The association of the DASH diet with odds of HUA was stronger among men (p-interaction = 0.009), non-Han Chinese (p-interaction< 0.001) as well as rural residents (p-interaction< 0.001). CONCLUSIONS: Our results illustrate that the DASH diet was remarkably negatively with SUA levels and odds of HUA in the Chinese adult population.

Rapid quality evaluation of Chinese herbal medicines using a miniature mass spectrometer: Lygodium japonicum (Thunb.) Sw. as an example.

The quality of Chinese herbal medicine (CHM) raw materials is essential, and mass spectrometry (MS)-based technologies have been playing key roles in the quality control of CHMs. However, the use of miniature mass spectrometry (mini-MS) for quality control of CHMs has rarely been reported. In this work, we developed a rapid analytical method for the quality evaluation of CHMs based on paper spray ionization (PSI)-mini-MS/MS. The quality evaluation of Lygodium japonicum (Thunb.) Sw. was used as an example. Following a "multi-component" quality evaluation strategy, nine active constituents of L. japonicum were selected to be used as analytes for quality control. We confirmed that the precursor-product ion information in the MS/MS spectra of each analyte in the herbal extracts was consistent with the standards. Also, we developed a mini-MS-based quantitative method for each analyte using its quantification ion. The quantitative methodology was rigorously validated using quality control samples. Finally, the quality evaluation of L. japonicum was carried out using the established MS/MS method combined with statistical analysis. A wide range of common quality issues with L. japonicum can be effectively determined, including whether it is adulterated with sand and distinguishing among different parts and species. This study demonstrates that mini-MS for quality evaluation of CHMs is feasible. Mini-MS for quality evaluation of herbal medicines will potentially have a good prospect due to its many advantages such as low cost, low power consumption, and portability in the future.

Analysis of Components and Properties of Extractives from Alnus cremastogyne Pods from Different Provenances.

Chemical components with anti-oxidant, anti-inflammatory, and anti-cancer properties extracted from Alnus bark and leaves have been extensively studied. However, less attention has been paid to extractives from Alnus pods, which are mostly treated as waste. Here, extractives of Alnus cremastogyne pods from 12 provenances in Sichuan Province were studied for high value-added utilization of Alnus waste. The extractives were analyzed by Gas Chromatography-Mass Spectrometer (GC-MS), Ultraviolet-visible spectroscopy (UV-Vis spectra), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity. A total of 58, 49, and 51 chemical components were found when the organic solvents of ethanol, petroleum ether, and ethyl acetate were used to collect extractives, respectively. These chemical components including Phytol, CIS-5,8,11,14,17-eicosapentaenoic acid, Germacrene D, Lupeol, and ß-sitosterol, etc., have wide applications in the fields of pharmacy and cosmetics. Moreover, it was also found that extractives in ethanol and ethyl acetate had impressive UV resistance, especially for UV-C and UV-B blocking. The results showed that the maximum block ratio towards UV-C and UV-B could reach 99%. In addition, the ethanol extract showed good anti-oxidant activity with a maximum free radical scavenging rate of 96.19%. This comprehensive and systematic study on extractives from Alnus cremastogyne pods promotes the development of high-value utilization of Alnus components.

Identification of molecular mechanisms underlying the therapeutic effects of Xintong granule in coronary artery disease by a network pharmacology and molecular docking approach.

Coronary artery disease (CAD) is a cardiovascular disease characterized by atherosclerosis, angiogenesis, thrombogenesis, inflammation, etc. Xintong granule (XTG) is considered a practical therapeutic strategy in China for CAD. Although its therapeutic role in CAD has been reported, the molecular mechanisms of XTG in CAD have not yet been explored. A network pharmacology approach including drug-likeness (DL) evaluation, oral bioavailability (OB) prediction, protein-protein interaction (PPI) network construction and analysis, and Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses was used to predict the active ingredients, potential targets, and molecular mechanisms of XTG associated with the treatment of CAD. Molecular docking analysis was performed to investigate the interactions between the active compounds and the underlying targets. Fifty-one active ingredients of XTG and 294 CAD-related targets were screened for analysis. Gene Ontology enrichment analysis showed that the therapeutic targets of XTG in CAD are mainly involved in blood circulation and vascular regulation. KEGG pathway analysis indicated that XTG intervenes in CAD mainly through the regulation of fluid shear stress and atherosclerosis, the AGE-RAGE signaling pathway in diabetic complications, and the relaxin signaling pathway. Molecular docking analysis showed that each key active ingredient (quercetin, luteolin, kaempferol, stigmasterol, resveratrol, fisetin, gamma-sitosterol, and beta-sitosterol) of XTG can bind to the core targets of CAD (AKT1, JUN, RELA, MAPK8, NFKB1, EDN1, and NOS3). The present study revealed the CAD treatment-related active ingredients, underlying targets, and potential molecular mechanisms of XTG acting by regulating fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, and relaxin signaling pathway.

Metal-organic framework on porous TiO2 thin film-coated alumina beads for fractional distillation of plant essential oils.

Fractionation of essential oils is technically challenging due to enormous scaffold diversities and structural complexities as well as difficulties in the implementation of the fractionation in the gas phase. Packing beads with multi-dimensional hierarchical nanostructures have been developed herein to pack fractional columns for atmospheric distillations. Activated alumina beads were coated with a porous TiO2 thin film. Growth of Cu-BTC (benzene-1,3,5-tricarboxylate) crystals in resultant porous surfaces leads to the generation of new nanopores and increased metal centers for differential coordination with diverse components of essential oils. The TiO2 thin film is not only an integral part of the composites but also induces the oriented growth of Cu-BTC metal organic framework (MOF) crystals through coordinative interactions. These Al2O3@TiO2@Cu-BTC MOF beads show very strong absorptive capability for major components of essential oils, except for a single cyclic ether eucalyptol with steric hindrances. The eucalyptol was fractionated by using the column packed with those modified alumina beads from raw materials of Artemisia argyi, and Rosmarinus officinalis with high purities up to 96% and 93%, respectively.

Revealing Calcium Signaling Pathway as Novel Mechanism of Danhong Injection for Treating Acute Myocardial Infarction by Systems Pharmacology and Experiment Validation.

Introduction: Danhong injection (DHI) is a traditional Chinese medicine preparation commonly used in the clinical treatment of acute myocardial infarction (AMI). In this study, the active components of DHI and its mechanism in the treatment of AMI were investigated. Methods: The chemical components of DHI were detected by the ultra-high-performance liquid chromatography-linear trap quadrupole-orbitrap-tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS/MS), and the targets and pathways of DHI in the treatment of AMI were analyzed by systems pharmacology, which was verified by molecular docking and animal experiments. Results: A total of 12 active components of DHI were obtained, and 158 common targets of component and disease were identified by systems pharmacology. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results showed that DHI is closely related to the calcium signaling pathway in the treatment of AMI. Molecular docking showed that the key target protein has good binding affinity to related compounds. The experimental results showed that compared with the model group, LVAWs, EF, and FS significantly (p < 0.05) increased in the DHI group. The percentage of myocardial infarction significantly (p < 0.01) decreased, both in the ventricular and total cardiac regions, and the pathological damage of myocardial tissue also decreased. In addition, the expression of the protein CaMK II decreased (p < 0.01) and the expression of SERCA significantly increased (p < 0.01). Conclusion: This study revealed that ferulic acid, caffeic acid and rosmarinic acid could inhibit AMI by regulating PLB, CaMK II, SERCA, etc. And mechanistically, calcium signaling pathway was critically involved. Combination of systems pharmacology prediction with experimental validation may provide a scientific basis for in-depth clinical investigation of the material basis of DHI.

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.

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.

Dissecting the novel mechanism of reduning injection in treating Coronavirus Disease 2019 (COVID-19) based on network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Reduning injection (RDNI) is a patented Traditional Chinese medicine that contains three Chinese herbal medicines, respectively are the dry aboveground part of Artemisia annua L., the flower of Lonicera japonica Thunb., and the fruit Gardenia jasminoides J.Ellis. RDNI has been recommended for treating Coronavirus Disease 2019 (COVID-19) in the "New Coronavirus Pneumonia Diagnosis and Treatment Plan". AIM OF THE STUDY: To elucidate and verify the underlying mechanisms of RDNI for the treatment of COVID-19. METHODS: This study firstly performed anti-SARS-CoV-2 experiments in Vero E6 cells. Then, network pharmacology combined with molecular docking was adopted to explore the potential mechanisms of RDNI in the treatment for COVID-19. After that, western blot and a cytokine chip were used to validate the predictive results. RESULTS: We concluded that half toxic concentration of drug CC50 (dilution ratio) = 1:1280, CC50 = 2.031 mg crude drugs/mL (0.047 mg solid content/mL) and half effective concentration of drug (EC50) (diluted multiples) = 1:25140.3, EC50 = 103.420 µg crude drugs/mL (2.405 µg solid content/mL). We found that RDNI can mainly regulate targets like carbonic anhydrases (CAs), matrix metallopeptidases (MMPs) and pathways like PI3K/AKT, MAPK, Forkhead box O s and T cell receptor signaling pathways to reduce lung damage. We verified that RDNI could effectively inhibit the overexpression of MAPKs, PKC and p65 nuclear factor-κB. The injection could also affect cytokine levels, reduce inflammation and display antipyretic activity. CONCLUSION: RDNI can regulate ACE2, Mpro and PLP in COVID-19. The underlying mechanisms of RDNI in the treatment for COVID-19 may be related to the modulation of the cytokine levels and inflammation and its antipyretic activity by regulating the expression of MAPKs, PKC and p65 nuclear factor NF-κB.

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 Danshen Class Injections for Treating Acute Coronary Syndrome: A Multidimensional Bayesian Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Acute coronary syndrome, that is a common and serious cardiovascular disease, imposes a huge economic burden on global public health. And Danshen class injections are commonly used in the treatment of acute coronary syndrome in China. Thus, the Bayesian network meta-analysis was devised to investigate the efficacy of different Danshen class injections against acute coronary syndrome. METHODS: Eligible inclusion and exclusion criteria were established in advance. Then, a systematic literature search was performed in several databases from inception to February 2020. Further, the included randomized controlled trials data were adopted to calculation, prepare graphs and multidimensional cluster analysis by WinBUGS 1.4.3, Stata V.13.0 and R 3.6.1 software, respectively. RESULTS: A total of 53 eligible randomized controlled trial studies with 6401 patients were obtained that evaluated the clinical effectiveness rate, the level of hypersensitive C-reactive protein, C-reactive protein, interleukin-6, fibrinogen, and adverse reactions after the application of Danshen class injections plus western medicine. Compared with western medicine alone, Danshen class injections combined with western medicine therapy were associated with significantly improved the therapeutic effect. In addition, the results of the multidimensional cluster analysis demonstrated that Danhong injection + western medicine and Danshen injection + western medicine had better therapeutic effects. However, since most eligible randomized controlled trial studies did not focus on the monitoring of adverse reactions, the safety of these Chinese herbal injections needs to be further explored. CONCLUSION: Based on this Bayesian network meta-analysis results, Danhong injection + western medicine and Danshen injection + western medicine might have a better impact on acute coronary syndrome patients. Nevertheless, more large samples, high-quality clinical and multicenter randomized controlled trial studies should be tested and verified in the future.

Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology.

Compound Kushen injection (CKI), a medicine in widespread clinical use in China, has proven therapeutic effects on cancer. However, few molecular mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network analysis with network pharmacology methods were undertaken to elucidate the underlying molecular mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clinical traits of ESCA were analysed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacology. Molecular docking simulation was performed to recognize the binding activity of hub genes with CKI compounds. The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the molecular mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment.

A bioinformatics investigation into molecular mechanism of Yinzhihuang granules for treating hepatitis B by network pharmacology and molecular docking verification.

Yinzhihuang granules (YZHG) is a patented Chinese medicine for the treatment of hepatitis B. This study aimed to investigate the intrinsic mechanisms of YZHG in the treatment of hepatitis B and to provide new evidence and insights for its clinical application. The chemical compounds of YZHG were searched in the CNKI and PUBMED databases, and their putative targets were then predicted through a search of the SuperPred and Swiss Target Prediction databases. In addition, the targets of hepatitis B were obtained from TTD, PharmGKB and DisGeNET. The abovementioned data were visualized using Cytoscape 3.7.1, and network construction identified a total of 13 potential targets of YZHG in the treatment of hepatitis B. Molecular docking verification showed that CDK6, CDK2, TP53 and BRCA1 might be strongly correlated with hepatitis B treatment. Furthermore, GO and KEGG analyses indicated that the treatment of hepatitis B by YZHG might be related to positive regulation of transcription, positive regulation of gene expression, the hepatitis B pathway and the viral carcinogenesis pathway. Network pharmacology intuitively shows the multicomponent, multitarget and multichannel pharmacological effects of YZHG in the treatment of hepatitis B and provides a scientific basis for its mechanism of action.

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.

Investigating the multi-target pharmacological mechanism of danhong injection acting on unstable angina by combined network pharmacology and molecular docking.

BACKGROUND: Danhong injection (DHI), which is one of the most well-known Traditional Chinese Medicine (TCM) injections, widely used to treat unstable angina (UA). However, its underlying pharmacological mechanisms need to be further clarified. METHODS: In the present study, network pharmacology was adopted. Firstly, the relative compounds were obtained by a wide-scaled literatures-mining and potential targets of these compounds by target fishing were collected. Then, we built the UA target database by DisGeNET, DigSee, TTD, OMIM. Based on data, protein-protein interaction (PPI) analysis, GO and KEGG pathway enrichment analysis were performed and screen the hub targets by topology. Furthermore, evaluation of the binding potential of key targets and compounds through molecular docking. RESULTS: The results showed that 12 ingredients of DHI and 27 putative known therapeutic targets were picked out. By systematic analysis, identified 4 hub targets (TNF, TLR4, NFKB1 and SERPINE1) mainly involved in the complex treating effects associated with coagulation and hemostasis, cell membrane region, platelet alpha granule, NF-kappa B signaling pathway and TNF signaling pathway. CONCLUSION: The results of this study preliminarily explained the potential targets and signaling pathways of DHI in the treatment of UA, which may help to laid a good foundation for experimental research and further clinical application.

Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology.

BACKGROUND: As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out. METHODS: In this study, we identified 16 active ingredients and 60 GC target proteins. Then, we established a compound-predicted target network and a GC target protein-protein interaction (PPI) network by Cytoscape 3.5.1 and systematically analyzed the potential targets of CKI for the treatment of GC. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. RESULTS: The results showed that the potential targets, including CCND1, PIK3CA, AKT1, MAPK1, ERBB2, and MMP2, are the therapeutic targets of CKI for the treatment of GC. Functional enrichment analysis indicated that CKI has a therapeutic effect on GC by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway. Moreover, molecular docking simulation indicated that the compounds had good binding activity to PIK3CA, AKT1, MAPK1, ERBB2, and MMP2 in vivo. CONCLUSION: This research partially highlighted the molecular mechanism of CKI for the treatment of GC, which has great potential in the identification of the effective compounds in CKI and biomarkers to treat GC.

Investigation on the Efficiency of Chinese Herbal Injections for Treating Non-small Cell Lung Cancer With Vinorelbine and Cisplatin Based on Multidimensional Bayesian Network Meta-Analysis.

Background: As non-small cell lung cancer (NSCLC) seriously threatens human health, several clinical studies have reported that Chinese herbal injections (CHIs) combined with vinorelbine and cisplatin (NP) are beneficial. This multidimensional network meta-analysis was performed to explore the preferable options among different CHIs for treating NSCLC. Methods: A literature search was performed in several databases to identify randomized controlled trials (RCTs) of CHIs in the treatment of NSCLC from inception to January 31, 2019. Final included studies met the eligibility criteria and methodological quality recommendations. Data analysis was performed using Stata 13.0 and WinBUGS 14.0 software. Each outcome was presented as an odds ratio and the surface under the cumulative ranking curve value (SCURA). The "scatterplot3d" package in R 3.6.1 software was used to perform multidimensional cluster analysis. Results: Ultimately, 97 eligible RCTs involving 7,440 patients and 14 CHIs were included in this network meta-analysis. Combined with NP chemotherapy, Kanglaite injection plus NP exhibited a better impact on the clinical effectiveness rate (SCURA probability: 78.34%), and Javanica oil emulsion injection plus NP was better in the performance status (95.44%). Huachansu injection plus NP was dominant in reducing thrombocytopenia (92.67%) and gastrointestinal reactions (92.52%). As to multidimensional cluster analysis, Shenmai injection plus NP was superior considering improving the clinical effectiveness rate, performance status and relieving leukopenia. Conclusions: The combination of CHIs and NP has a better impact on patients with NSCLC than NP alone. Among them, Shenmai injection plus NP, Kanglaite injection plus NP and Javanica oil emulsion injection plus NP were notable. Nevertheless, more multicenter and better designed RCTs are needed to validate our findings.

Antioxidant and Tyrosinase Inhibitory Activities of Seed Oils from Torreya grandis Fort. ex Lindl.

Torreya grandis Fort. ex Lindl. is a plant belonging to the Taxaceae family and Torreya grandis cv. Merrillii is the only grafted and thoroughbred species belonging to this species. In this study, we extracted five different seed oils, including T. grandis seed oil (TGSO), T. grandis "Xiangyafei" seed oil (XYSO), T. grandis "Zhimafei" seed oil (ZMSO), T. grandis "Majus"seed oil (TGMSO), and T. grandis "cunguangfei" seed oil (CGSO) using physical pressure. The resulting extracts were analyzed to determine their fatty acid composition, antioxidant activity, and inhibitory activity towards tyrosinase. The results of the antioxidant activity assays revealed that XYSO and ZMSO exhibited much greater DPPH radical scavenging activity and ferric reducing power than TGSO. Notably, all five of the seed oils showed dose-dependent inhibitory activity towards tyrosinase. XYSO and TGSO gave the highest activities of all of the seed oils tested in the current study against monophenolase and diphenolase, with IC50 values of 227.0 and 817.5µg/mL, respectively. The results of this study show that wild TGSOs exhibit strong antioxidant and tyrosinase inhibition activities. These results therefore suggest that wild TGSOs could be used as a potential source of natural antioxidant agents and tyrosinase inhibitors.