Study On The Antihypertensive Effect Of Salvia Miltiorrhiza Compound Based On Network Pharmacology And Experimental Verification

Hypertension is an epidemic that threatens human health all over the world,at present,the global prevalence is generally on the rise and patients are getting younger.Therefore,our task of preventing and treating hypertension is very difficult.In recent years,phytochemical resources have received more and more attention,with wide resources and few side effects,and have broad application prospects.Salvia miltiorrhiza compound is based on the theory of traditional Chinese medicine,which is composed of Salvia miltiorrhiza,Panax notoginseng,Semen cassiae torae,Crataegus pinnatifida and Ligusticum chuanxiong.It has certain therapeutic effect on patients with hypertension,but there is no detailed data to support it and its application is limited.In this paper,Salvia miltiorrhiza compound is taken as the research object,and the theoretical basis of antihypertensive effect is analyzed by network pharmacology,then the antihypertensive effect and possible hypotensive mechanism are verified according to the in vitro and in vivo experiments,which provides a scientific basis for its rational development and utilization.The main research results are as follows:（1）Based on network pharmacology,we analyzed the Salvia miltiorrhiza compound and screened 106 active compounds,221 potential targets,and 83 possible pathways.GO analysis found that potential targets can act on blood pressure regulation,smooth muscle contraction,nitric oxide biosynthesis,antioxidants,regulation of myocardial tissue growth and other biological processes closely related to hypertension.KEGG metabolic pathway shows that Salvia miltiorrhiza compound mainly acts on vascular endothelial growth factor pathway,vascular smooth muscle contraction pathway and oxidative stress pathway which can regulate endothelial dysfunction,promote the release of vasodilators and regulate glycolipid metabolism,so as to reduce blood pressure.（2）Through in vitro experiments,it was found that Salvia miltiorrhiza compound has good reducing power and scavenging effect on DPPH,O₂^-and OH free radicals;it has the ability to combine sodium taurocholate,sodium glycocholate and sodium cholate;it has an inhibitory effect on angiotensin converting enzyme with an IC₅₀ of 19.32 mg/mL.（3）The model of hypertensive rat was induced by high-salt,high-fat,high-fructose diet.At the end of the eighth week,the SBP of the rats in the diet-induced group reached 150-175 mmHg,and the DBP reached 120-135 mmHg,which were significantly higher than those in the blank control group.（4）The salvia miltiorrhiza compound has a significant antihypertensive effect on hypertensive rats,and the high dose group has the best effect,SBP and DBP were decreased to 140 mmHg and 118 mmHg respectively.By detecting blood and organ indicators in hypertensive rats,it was found that:1)Salvia miltiorrhiza compound could significantly reduce the content of Vasoconstriction factor,the levels of Renin,AngII and ET-1 in the high dose group were decreased by 18.37%,38.12%and37.94%,respectively;2)The content of vasodilator factor and the activity of eNOS were significantly increased,the NO content in the high dose group was increased52.24%;3)Left ventricular hypertrophy index and cardiac coefficient were significantly decreased in high dose group;4)It can regulate blood lipid and blood sugar,the contents of TG,TC,LDL-C,insulin and uric acid were reduced,but the level of HDL-C was increased;5)The oxidative stress was regulated,the activity of SOD and GSH-Px were increased,and the content of MDA was decreased.The above results suggest that Salvia miltiorrhiza compound can regulate the RAS system and endothelial function of hypertensive rats,balance vasoconstriction and vasodilator factor,and then regulate the abnormal metabolism of glucose and lipid and improve oxidative stress,through many aspects of synergetic effect to play a role in lowering blood pressure.