Functional Mechanism And Clinical Observatio Of Wumei Pill In Treating Essential Hypertension Based Of Network Pharmacology

Objective:To explore the clinical efficacy,main pathway,related targets and internal mechanism of Wumei Pill in the treatment of primary hypertension with upper heat and lower cold syndrome,so as to provide theoretical and practical basis for clinical medication of Wumei Pill.Methods:1.clinical efficacy observation:72 patients with high blood pressure,upper and lower heat and cold syndrome were randomly divided into control group and experimental group,36 cases in each group,valsartan capsule in control group,valsartan capsule combined with Wumei Pill in the experimental group.The intervention was 4 weeks.Before and after treatment,the improvement of blood pressure value and syndrome score were observed.2.network pharmacology research:Based on the data platform,the components and targets of all drugs in Wumei pills are aggregated to screen the key components;the targets of essential hypertension are obtained from each database,and the two targets are mapped by Wayne map;the interaction relationship and enrichment pathway of the mapping results are obtained by using string and David databases to obtain the pathway and key targets of the antihypertensive effect of Wumei pills.3.Verification of key target expression:the serum of the experimental group and the control group before and after treatment was collected for ELISA test to observe the effect of Wumei Pill on the protein expression of key targets(VEGFA,EGFR,CXCL8,NOS3,CXCL10).Results:1.Clinical efficacy observation:Wumei Pill can play an auxiliary and enhancing role in the clinical efficacy of valsartan capsule in the treatment of primary hypertension with upper heat and lower cold syndrome,improve the blood pressure value and syndrome score of the experimental group,the effect is better than that of the control group(P<0.05),and has good safety.2.Network pharmacology:115 active components and 280 matching targets were obtained.Network topology analysis showed that there were 11 key components.2455 hypertension related targets were obtained,186 potential targets were obtained by mapping,and 11 key targets were extracted for molecular docking verification,which showed that the key components and targets could be well combined.In the enrichment analysis,the pathways related to hypertension involve the classical PI3K Akt,MAPK and Ca2+ signaling pathways,Energy metabolism pathways such as FOXO and HIF-1,erbB signaling pathway acting on the central nervous system,TNF and Toll receptor signaling pathways in immunity,smooth muscle contraction and vascular endothelial growth factor signaling pathways closely related to vascular remodeling,aldosterone sodium reabsorption pathway regulating water and sodium balance,and cell apoptosis and cell cycle are also involved The changes of cell cycle and extracellular matrix.Some key targets are to be further verified.3.Verification of key targets:before treatment,there was no difference in serum targets between the experimental group and the control group.After 4 weeks of drug intervention,the expression of VEGFA,EGFR,CXCL8 and CXCL10 in the above key targets was down regulated,while the expression of NOS3 was up-regulated,and the trend change was better than that in the control group(P<0.05).Conclusion:Wumei Pill has no obvious adverse effect on the treatment of the upper and lower heat cold syndrome of essential hypertension.It is found that the mechanism of its antihypertensive effect is related to down regulation of VEGFA,EGFR,CXCL8 and CXCL10,up-regulation of NOS3,involving the biological process of vascular remodeling and immunoregulation.This study provides theoretical support and clinical basis for the clinical application of Wumei Pill in the treatment of essential hypertension.