Effects Of ’Liang Guanxi’ Herb Pair Salvia Miltiorrhiza-Borneol Against Cerebral Ischemia

Stroke is a disease that causes damage to brain tissue due to blockage or rupture of blood vessels in the brain.It has the characteristics of ‘four highs and one low’,and its disability rate ranks first.Salvia miltiorrhiza is a classic herb for promoting blood circulation and removing blood stasis.Borneol can awaken the mind,clear heat and relieve pain.The combination of the two herbs can dilate blood vessels,increase blood flow,and treat cardiovascular and cerebrovascular diseases.In this paper,the ‘Liang Guanxi’ herb pair derived from the compound Salvia miltiorrhiza prescription was used as the research object to investigate the anti-cerebral ischemia efficacy of Salvia miltiorrhiza-borneol,and the brain substance basis of Salvia miltiorrhiza-borneol against cerebral ischemia injury was studied from the aspects of metabolism,as follows:1.In this study,the middle cerebral artery occlusion model was prepared by the method of thread embolization,and the effects of salvia miltiorrhiza and borneol on cerebral ischemia injury were investigated from the aspects of rat behavior,brain water content,cerebral infarction area and inflammation.The results showed that salvia miltiorrhiza,borneol and their combination could reduce behavioral score,cerebral water content and cerebral infarction area,and alleviate cerebral ischemia injury in rats,and the improvement effect of salvia miltiorrhiza-borneol combination group was better.After cerebral ischemia,IL-6,IL-1β,TNF-α,NO inflammatory factors were significantly increased,and the combination of Salvia miltiorrhiza and borneol showed improvement to a certain extent.2.In this study,the effects of salvia miltiorrhiza-borneol on cerebral ischemic injury were studied by using the method of UPLC-Q-TOF/MS in rat brain tissue.It was found that after cerebral ischemia occurred,the levels of 33 endogenous substances in rat brain tissue changed significantly.Salvia miltiorrhiza-borneol can improve the disorder of 24 kinds of endogenous substances,Salvia miltiorrhiza can improve 6 kinds,and borneol can improve 5kinds.In contrast,the Salvia miltiorrhiza-borneol group can reverse more cerebral ischemia-related differential endogenous substances,The results were consistent with the results of pharmacodynamics,involving Amino acid metabolism,Fatty acid metabolism,Energy metabolism and other pathways.At the same time,the metabolites of Salvia miltiorrhiza-borneol into the brain were found to be Salvia miltiorrhizasu isopropyl ester(IDHP)and caffeic acid isopropyl ester(KYB).3.This study uses network pharmacology to explore the mechanism of potential medicinal components of Salvia miltiorrhiza-borneol on the anti-cerebral ischemia injury.Combining content detection with TCMSP and other databases,14 components of Salvia miltiorrhiza-borneol were obtained.The intersection of their targets and disease targets yielded a total of111 anti-cerebral ischemia targets,such as AKT1,TNF,VEGFA,EGFR,TP53,IL2,IL4,etc.They are involved in cell growth,death(apoptosis),angiogenesis,expression and regulation of immune responses,etc.The components of Salvia miltiorrhiza-borneol play an anticerebral ischemia effect by regulating oxidation,immune response and neuroinflammation.4.In this study,UPLC-QQQ-MS/MS was utilized to compare the tissue distribution of salvianic acid,rosmarinic acid,caffeic acid,protocatechuic acid,protocatechuic aldehyde,salvianolic acid A and metabolites IDHP and KYB in brain tissue samples from rats with cerebral ischemia in the Salvia miltiorrhiza group and Salvia miltiorrhiza-borneol group with time series.It was found that borneol increased the contents of IDHP,KYB salvianic acid and other phenolic acids in brain,suggesting that borneol could promote the anti-cerebral ischemia effect of Salvia miltiorrhiza.The correlation between ester formation and phenolic acids and amino acids was discussed by means of causal mathematical model.The metabolites IDHP and KYB were found to be causally related to caffeic acid,salvianic acid and other pharmaceutical components and amino acids such as Threonine and Lysine.