Exploration Of The Mechanism Of Sanqi And Danshen In Treating Coronary Heart Disease Based On Multiple Omics

Sanqi and Danshen are typical representatives of traditional Chinese medicine(TCM)that enhance blood circulation and alleviate blood stasis.They have been extensively applied in treating cardiovascular diseases,particularly CHD.Shenqixinshu capsule(SQXS)is a commonly used Chinese patent medicine,that is a prescription of traditional Yi medicine and modern clinical medicine.Although these traditional Chinese medicines have shown certain therapeutic effects in clinical practice,their mechanisms of action are still unclear.CHD is a common and serious cardiovascular disease with a high incidence and mortality rate.The causes of CHD include high-fat and high-sugar diets,unhealthy habits.At the same time,it is also related to imbalanced metabolism and coronary atherosclerosis in the human body,which may ultimately lead to ischemic heart disease.Atherosclerosis is also accompanied by immune reactions,bacterial infections,acute myocardial infarction,and other complications.Currently,a combination of medication and surgery is mainly used for the treatment of CHD.Although statins and vascular surgery have good effects,patients may experience pulmonary dysfunction after surgery,and there may be problems such as no reflow after vascular reconstruction and high recurrence rate and mortality rate after myocardial infarction.Traditional Chinese medicine(TCM)possesses significant strengths in preventing and treating CHD,easing angina pectoris,and reducing the risk of recurrence after coronary artery surgery.As a result,it is of paramount importance to discover effective TCM for promoting blood circulation and removing blood stasis,as well as to elucidate their mechanisms of action in treating CHD.This study used a rat model of coronary heart disease and employed multidimensional techniques including network pharmacology,pharmacology,metabolomics,and metagenomics to systematically investigate the therapeutic effects and mechanisms of action of Sanqi,Danshen,SQXS,and the commonly used traditional Chinese medicine Compound Danshen Dripping Pills on rats with CHD.This study offers scientific evidence that can enhance the clinical management of CHD through the integration of traditional Chinese medicine.Furthermore,the research methodologies and concepts employed in this study serve as a reference for investigating the therapeutic effects and underlying mechanisms of action of other traditional Chinese medicines.The main findings of this study are as follows:1.Exploring the mechanisms of Sanqi and Danshen in treating CHD based on network analysis.According to network analysis,Sanqi is predicted to target 184 proteins while Danshen is predicted to target 103 proteins in the treatment of CHD.The PI3K/AKT signaling pathway is the major pathway for CHD treatment with both Sanqi and Danshen.Ginsenoside Rh2 and tanshinone ⅡA,which are closely associated with the main pathway,are the principal active components of Sanqi and Danshen,respectively.2.Exploring the mechanisms of SQXS in the treatment of CHD based on network analysis.Based on network analysis,the active ingredients,target proteins,and action pathways of SQXS in the treatment of CHD were predicted.The main active components of SQXS include tanshinone ⅡA,ginsenoside Rh2,quercetin,kaempferol,luteolin,beta-sitosterol,naringenin,etc.It regulates 220 target proteins and modulates processes such as lipid,nitrogen compound,and hypoxia response of cells.The main signaling pathway is the PI3K/AKT signaling pathway.3.Mechanisms of different drugs in treating CHD in ratsUsing healthy rats as controls and rats with CHD as models,the therapeutic effects of four drugs on CHD rats were compared.The results showed that all four drugs could reduce the serum lipid levels of CHD rats and increase the expression and activation of PI3K and AKT1 proteins,indicating that all four drugs could treat CHD.Ginsenoside Rh2 significantly reduced serum TG factor levels,while tanshinone ⅡA was better than ginsenoside Rh2 and SQXS in reducing serum LDL factor levels.SQXS was better than postive group in reducing serum TG and HDL factor levels.A marked elevation in the levels of PI3K,AKT1,and p-AKT1 proteins was noted in all four treatment groups(pvalue<0.05)as compared to the disease group.The p-PI3K protein levels in the tanshinone ⅡA group were significantly increased,while the p-PI3K protein levels in the other treatment groups were also increased but not significantly different.The findings revealed that the four drugs activated the PI3K/AKT signaling pathway,thereby treating CHD in rats via pathways such as reduction of blood lipid levels and regulation of PI3K/AKT signaling pathway-related protein expression.4.Effects of different drugs on serum metabolites in CHD ratsBased on serum metabolomics,significant differences were found in the metabolite levels between disease rats and health rats,with 48 differential metabolites involved in the rat’s phospholipid metabolism,fatty acid metabolism,amino acid metabolism,and organic acid metabolism pathways.Ginsenoside Rh2 mainly exerted its therapeutic effect on CHD by affecting the pentose phosphate pathway,carbon metabolism pathway,and pyrimidine metabolism pathway.Tanshinone ⅡA mainly exerted its therapeutic effect on CHD by affecting the biosynthesis of secondary metabolites,glyoxylate and dicarboxylate metabolism pathway,and microbial metabolism in diverse environments.SQXS and positive group mainly exerted its therapeutic effect on CHD by affecting the pentose phosphate pathway,carbon metabolism pathway,and vitamin B6 metabolism pathway.5.Effects of different drugs on gut microbiota in CHD ratsUsing 16S rRNA sequencing,it was found that CHD caused dysbiosis of the gut microbiota in rats,characterized by an elevation in the proportion of Proteobacteria and a reduction in the relative abundance of Firmicutes and Bacteroidetes.The dominant bacterial genera also underwent significant changes,with Lactobacillus and Escherichia-Shigella significantly increased in CHD rats compared to normal rats.After intervention with the four drugs,the number of beneficial bacterial phyla in the gut of CHD rats increased,and the abundance of harmful bacterial phyla decreased.