Exploring the mechanism of action of Wuzhuyu Decoction for vascular headache based on network pharmacology and molecular docking

Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal medicine,and the Gendcars,OMIM,PharmGKB,TTD,and DrugBank databases were used to screen for disease targets.We constructed the PPI network of targets by utilizing the String database,and GO and KEGG analyses were performed.The"drug-ingredient-target-disease"network diagram was constructed using Cytoscape 3.8.0 software.We analyzed the topological parameters to identify the primary active ingredients and targets of Wuzhuyu Decoction,and subsequently confirmed the findings via molecular docking.Results:A total of 86 active ingredients were obtained,including Quercetin,Kaempferol,Beta-sitosterol,Stigmasterol,and Nuciferin.Fourteen core targets were identified,including JUN,TP53,AKT1,RELA,MAPK1,MAPK14,MYC,MAPK8,CCND1,ESR1,CTNNB1,FOS,NR3C1,and RB1.GO enrichment analysis involved biological processes such as response to drug,response to lipopolysaccharide,and response to molecule of bacterial origin.The cellular components were membrane raft and membrane microdomain,and the molecular functions were catecholamine binding and nuclear receptor activity.The KEGG pathway enrichment analysis demonstrated the potential regulation of 171 pathways by Wuzhuyu Decoction.including the Lipid and atherosclerosis signaling pathway,the Fluid shear stress and atherosclerosis signaling pathway,and the PI3K-AKT signaling pathway.Molecular docking showed that Nuciferin had good binding activity with AKT1(-9.9 kJ/mol),as did Quercetin with AKT1(-9.8 kJ/mol),Stigmasterol with MAPK1(-9.7 kJ/mol),and Kaempferol with AKT1(-9.5 kJ/mol).Conclusion:Wuzhuyu Decoction may exert its therapeutic effect on vascular headache by inhibiting neurogenic inflammation,providing analgesia,and modulating the immune system.

Pregnane receptor gene polymorphisms,pathogenic bacteria distribution and drug sensitivity,and TCM dyndrome differentiation in patients with cholelithiasis

Objective:To investigate the distribution of pathogens and drug resistance in bile and the association between the pregane X receptor(PXR) gene polymorphisms,traditional Chinese medicine(TCM) syndromes and the risk of cholesterol gallstone disease(CGD).Methods:A total of 392 samples were enrolled in this study from January 2014 to February 2015.among which 192 patients were with CGD.and 200 samples were healthy.Strains were isolated and susceptibility testing was the disk diffusion method susceptibility testing.The patients were divided into hepatochlic hygropyrexia.stagnation of liver-qi.and the accumulation of damp.The PXR gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism.The association between the PXR gene polymorphisms and the risk of CGD was examined by logistic regression analysis.Results:A total of 192 cases were detected in 230 of bile culture pathogens,including Grain-negative bacteria 133(57.83%),Gram-positive bacteria76(33.04%),and fungi 21(9.13%).The top five pathogens were Escherichia coli,Klebsiella pneumoniae.Enterococcus faecalis,Candida albicans,and Enterococcus feces,ot which 110 cases was of single infection.48 cases of mixed infection of two strains,eight cases of mixed infection of three bacteria.Among 59 Escherichia coli,the yield extended-spectrum beta-laetamases had 40(67.80%).The hepatochlic hygropyrexia was the most TCM syndrome,followed by stagnation of liver-qi.and the accumulation of damp was least.Different pathogens and the rs6785049 genotypes distributed differently in cholelithiasis patients with different TCM syndromes(P<0.05).In hepatochlic hygropyrexia patients the Gram-negative bacteria was most.There was significant differences between CGD group and control group in rs6785049(P<0.001).Comparison with wild-type portable GG.GA genotype increased the risk of the occurrence of gallstones(OR=0.40.95%CI:0.16-0.79);likewise,carrying the GA + AA genotype also increased the risk(OR=0.38,95%CI:0.19-0.81).There was no significant differences in rs2276707,rs3814055 site polymorphic loci alleles in CGD group and control group.Conclusions:In the treatment of cholelithiasis,bile samples should be collected for bacterial culture and sensitivity test,and drugs should be strictly chosen based on the results.The rs6785049 polymorphisms in PXR gene may increase the risk of gallstones ontogeny,and gallstones can he early detected and prevented by detecting genotypes.rs6785049 polymorphisms in PXR gene may has relationship with TCM syndromes.

Effect of emodin on mobility signal transduction system of gallbladder smooth muscle in Guinea pig with cholelithiasis

Objective: To study the effect of emodin on protein and gene expressions of the massagers in mobility signal transduction system of cholecyst smooth muscle cells in guinea pig with cholesterol calculus. Methods: The guinea pigs were randomly divided into 4 groups, such as control group, gall-stone(GS) group, emodin group and ursodesoxycholic acid(UA) group. Cholesterol calculus models were induced in guinea pigs of GS, emodin and UA groups of induced models by lithogenic diet, while emodin or UA were given to the corresponding group for 7 weeks. The histomorphological and ultrastructure change of gallbladder were detected by microscope and electron microscope, the content of plasma cholecystokinin(CCK) and [Ca^(2+)]i were analyzed successively by radioimmunoassay and flow cytometry. The protein and mR NA of Gsα, Giα and Cap in cholecyst cells were determined by western blotting and real time polymerase chain reaction(RT-PCR). Results: Emodin or UA can relieve pathogenic changes in epithelial cells and muscle cells in gallbladder of guinea pig with cholesterol calculus by microscope and transmission electron microscope. In the cholecyst cells of GS group, CCK levels in plasma and [Ca^(2+)]i decreased, the protein and m RNA of GS group were downregulated,the protein and m RNA of Gi and Cap were up-regulated. Emodin significantly decreased the formative rate of gallstone, improved the pathogenic change in epithelial cells and muscle cells, increased CCK levels in plasma and [Ca^(2+)]i in cholecyst cells, enhanced the protein and mR NA of Gs in cholecyst cells, reduced the protein and mR NA of Gi and Cap in cholecyst cells in guinea pig with cholesterol calculus. Conclusion: The dysfunction of gallbladder contraction gives rise to the disorders of mobility signal transduction system in cholecyst smooth muscle cells, including low content of plasma CCK and [Ca^(2+)]i in cholecyst cells, abnormal protein and mRNA of Gs, Gi and Cap. Emodin can enhance the contractibility of gallbladder and alleviate cholestasis by regulating plasma CCK levels, [Ca2+]i in cholecyst cells and the protein and mR NA of Gs, Gi and Cap.

Albiflorin Granule significantly decreased the cholesterol gallstone formation by the regulation of insulin transduction signal

Objective:To study the mechanism of insulin resistance in the cholesterol gallstone formation from insulin signal transduction pathway so as to reveal the possible mechanism and the effective role of Albiflorin Granule on preventing the cholesterol gallstones.Methods:Serum triglycerides(TG),free fatty acid(FFA),and total cholesterol(TC) from different groups were measured and liver cells Ins R,PKB,IKK-β protein expression levels were detected by western blotting.Results:Albiflorin significantly decreased the cholesterol gallstone formation rate,increased glucose infusion rate in gallstone guinea pigs and improved insulin resistance.Compared with the normal group,insulin receptor and PKB protein expression in GS group were significantly reduced.IKK-β protein in the GS group increased significantly and Albiflorin could reduce IKK-β protein expression in guinea pig liver cells.Conclusions:The model of insulin resistance in cholesterol gallstone guinea pig was successfully established,which plays an important role in the cholesterol gallstone formation.All aspects of insulin signaling pathway are involved in gallstone formation.Albiflorin can regulate various aspects of insulin signal transduction pathway to prevent the formation of gallbladder.

Consensus statement on layout and delivery of automatic external defibrillator in China

1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symptoms that are atypical and not easily detected[1].According to a recent study,nearly 544000 patients suffer from SCD every year in China[2].

Analysis of mechanisms of Shenhuang Granule in treating severe COVID-19 based on network pharmacology and molecular docking

Objective:Severe cases of coronavirus disease 2019(COVID-19)are expected to have a worse prognosis than mild cases.Shenhuang Granule(SHG)has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial,but the active chemical constituents and underlying mechanisms of action remain unknown.The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19,using network pharmacology.Methods:Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG.Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform,Swiss Target Prediction,and Gene Expression Omnibus(GEO)databases.The target protein–protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms.Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets.Results:Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets,including hub genes such as HSP90AA1,MMP9,CXCL8,PTGS2,IFNG,DNMT1,TYMS,MDM2,HDAC3 and ABCB1.Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction,calcium signaling pathway and c AMP signaling pathway.Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets.Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase.Conclusion:Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways;this provides a scientific basis for clinical applications and further experiments.