Study On The Effect Of PDG In Regulating SHR Renin Synthesis And Substance Metabolism

Pinoresinol Diglucoside(PDG)is a lignan component mainly found in Eucommia ulmoides.In 1976,Sih first mentioned that PDG has anti-hypertensive activity in the paper about PDG separation and synthesis.How does PDG exert anti-hypertensive effect in the body? Is PDG the main anti-hypertensive component in Eucommia? Our previous study found that PDG can reduce the blood pressure of Spontaneously Hypertensive Rats(SHR),significantly reduce the activity of renin in the blood,promote the release of NO,reduce the content of Ang II,and then exerts anti-hypertensive effect by Renin-angiotensin-aldosterone system(RAAS).PDG also improves myocardial function and has no effect on blood pressure and heart rate of normal animals.In this paper,systematic pharmacology,molecular docking technology,molecular biology technology,metabolomics technology and other methods to further study the mechanism of PDG regulation of renin activity.What is the effect of PDG on the metabolism of endogenous substances in hypertensive state? To provide a reference for further clarifying the antihypertensive effect of PDG.1.Using the Systematic Pharmacology TCMSP Analysis Platform to predict potential targets of PDG-related compounds,obtain target-related diseases through the CTD database,and map drug-target-disease networks using Cytoscape(version 3.7.1)software,through network topology The interaction relationship of the target was analyzed,and the DAVID database was used to perform path enrichment analysis on all predicted proteins to obtain the main action pathway information associated with the target.Molecular docking techniques are used to predict the binding of potential targets to the binding of active ingredients to identify key targets.Results 14 potential targets were screened and 10 potential targets were used to intervene in hypertensive diseases.According to the possible target,9 pathways were speculated.Molecular docking results showed that PDG-related compounds might bind closely to CREB,RENIN and CTSB,which were the key factors regulating renin.2.Animals were divided into WKY blank group,SHR Mod.group,captopril positive control PL group,high dose PDG-L group,medium dose PDG-M group,and low dose PDG-S group.Large,medium,and small doses were given intraperitoneal injection of PDG in SHR for four weeks.After four weeks of blood and major organ tissues,the m RNA levels of CREB and RENIN in renal tissues were determined by RT-PCR.The results showed that PDG could inhibit the relative expression of CREB and RENIN m RNA.3.The optimized HPLC-Q-TOF-MS technique was used to analyze the endogenous substances in SHR plasma.The results showed that compared with WKY blank group animals,There were 16 significant changes in endogenous substances in SHR plasma,and PDG was able to improve these changes to varying degrees.The metabolic pathways involved in 16 endogenous substances include glycerophospholipid metabolism,fatty acid metabolism pathway,biosynthesis of unsaturated fatty acids,and ?-linolenic acid metabolic pathway.This study demonstrates that PDG can regulate the gene levels of key factors CREB and RENIN in the renin secretion pathway,inhibit the synthesis and secretion of renin,reduce the content of Ang II,lower blood pressure by affecting the RAAS system,and reduce the blood pressure of PDG.Phospholipid metabolism,fatty acid metabolism and other pathways.