Professor Hu Jingqing Based On The Theory Heat Retention In Blood Vessels Treated Angina Pectoris With Coronary Heart Disease Medication Rule And Its Mechanism

Objective: This study summarized medication rule and core prescription that Professor Hu Jingqing treated angina pectoris with coronary heart disease by the theory of heat retention in blood vessels.There were that applied the network pharmacology method to explore the potential mechanism of action of JXAM decoction for the treatment of CHD,verified the target and mechanism of action of JXAM decoction in animal experiments and explored the effective dose of the drug.Method:1.Based on data mining technology was summarized Professor Hu Jingqing’s medication rules for angina pectoris with CHD.Patients attending the outpatient clinic of Professor Hu Jingqing from 2018 to 2023,consistent with a diagnosis of angina pectoris with CHD.The medical records are included and analyzed statistically through the Ancient and Modern Medical Records Cloud Platform.Through drug frequency,drug attribute,association analysis,cluster analysis,complex network analysis and so on,we summarized the medication rule and core prescription of Professor Hu Jingqing in the treatment of angina pectoris with CHD by the theory of heat retention in blood vessels.2.Based on network pharmacology to explore the potential mechanism of the effect of JXAM decoction on CHD.Eight Chinese herbal ingredients of JXAM were screened for active compounds with OB > 30% and DL > 0.18,using molecular target prediction model database to support vector > 0.8 and random forest algorithm > 0.7,Cytoscape software was applied to construct drug ingredient-target network,Genecards and OMIM database to screen CHD targets,topological analysis of drug-disease target network,>2 times Degree value as the threshold,to obtain the core network targets,DAVID database for GO and KEGG enrichment analysis of core network targets.3.To explore the regulatory effects of JXAM decoction on I/R rats based on inflammation and gut microbiota.Myocardial I/R rats were used as a model.72 rats were randomly divided into control group of 12 rats and surgical group of 60 rats,and after modeling,they were randomly divided into I/R group,JXAM decoction low,medium and high dose group(JXAM-L/M/H),Positive group(Positive),and 4 weeks after administration,the samples were taken and tested.HE staining of myocardial and colonic tissues,horseshoe crab reagents for serum LPS,ELISA for inflammatory factors,Western-Blot for protein expression,16 s r DNA high-throughput sequencing of gut microbiota,and Spearman correlation for inflammation-bacteria association analysis.Results: 1.This study included a total of 216 prescriptions,among which male patients accounted for 69.91% and female 30.09%,and elderly patients accounted for 63.43% that aged 60 and above.The top 10 most frequently used Chinese medicines are Jinyinhua(Lonicera japonica Thunb 69.44%),Danshen(Salvia miltiorrhiza Bunge 67.59%),Danggui(Angelica sinensis 59.72%),Gancao(Liquorice,Licorice Root 48.61%),Xuanshen(Scrophularia ningpoensis Hemsl.47.69%),Guizhi(Ramulus Cinnamomi 43.06%),Lianqiao(Forsythia suspensa 40.74%),Huanglian(Coptis chinensis 33.80%),Huzhang(Reynoutria japonica Houtt.32.87%),Fuling(Poria 32.41%).The four qi are mostly warm and slightly cold,the five flavors are mainly sweet,spicy,and bitter,the meridian return are mainly focused on the lungs,heart,and stomach,and the medicinal efficacy is mainly to clear heat and detoxify.Association analysis showed that Jinyinhua,Danshen,Danggui,Xuanshen and Gancao had strong internal correlation.Cluster analysis can be divided into 7 categories,the first category is Jinyinhua,Danshen,the second category is Lianqiao,Huzhang,Gancao,Danggui,Xuanshen,the third category is Huanglian,Gegen,the fourth category is Fabanxia,Sharen,Tanxiang,Zhiqiao,Xiebai,Gualou,the fifth category is Fuling,Baizhu,Huangqi,the sixth category is Guizhi,the seventh category is Dihuang,Maidong,Wuweizi,Dangshen,Shanzhuyu,Chaihu,Taoren,Honghua.The core prescription was obtained by complex network analysis,which was based on Si-Miao-Yong-An Decoction plus Lianqiao,Huzhang,Danshen and Guizhi.2.The database collected 214 compounds and corresponding 3345 targets of 8 herbs of JXAM decoction.There are common compound of JXAM that beta-sitosterol,sitosterol,quercetin,kaempferol,luteolin,Stigmasterol,sugiol,Mairin,(+)-catechin.CHD had 3529 targets.PPI networks were mapped using Cytoscape software,201 targets at the intersection,intersection network greater than 2 times Degree value as a condition to obtain core targets,36 core targets were obtained,there are mainly that interleukin family,MMP9,MMP2,MAPK3,MAPK8,NFKBIA,NOS3,PTGS2,MCP-1,ICAM1,AKT1,TP53,MYC,CCND1,VEGF,EGFR,EGF,ESR1 and so on.There are mainly lipopolysaccharide reaction,inflammatory reaction and so on in the biological process.KEGG enrichment pathway mainly includes pathways in cancer,fluid shear stress and atherosclerosis,NF-κB signaling pathway,etc.3.Myocardial HE staining showed myocardial fiber destruction and inflammatory cell infiltration in the I/R group.Myocardial damage was obvious in the I/R group,and the model was prepared successfully.JXAM-M group and JXAM-H group showed significant improvement in myocardial,the improvement in JXAM-H group was similar to that in Positive group.Colon HE staining showed mucosal damage,villus structure changes and inflammatory cell infiltration in I/R group,JXAM-M group,JXAM-H group and Positive group showed obvious improvement.There were determine serum LPS,tissue homogenate inflammatory cytokines TNF-α,IL-6,IL-1β,IL-17 A,the expression was significantly increased in the I/R group,IL-17 A expression was statistically different only in JXAM-H group,other detection indexes were significantly decreased in JXAM-M group,JXAM-H group and Positive group.The inhibition of TLR4/NF-κB pathway by JXAM decoction showed a drug dependence trend,the higher the dose,the more obvious the inhibition of inflammatory protein expression,JXAM-M group and JXAM-H group was more significant inhibition effect.16 s r DNA high throughput sequencing results showed,I/R group were higher of species diversity and uniformity.Compared to the I/R group,in addition to JXAM-L group was slightly higher,the other three groups all declined approximatively to the Control group.At the level of phylum and genus,there were different degrees of change.According to the correlation analysis between different bacterial gut microbiota and inflammatory factors,in JXAM-M and JXAM-H groups enriched Bacilli,Lactobacillaceae,Lactobacillales,Lactobacillus,Actinobacteria,that were negatively correlated with serum LPS.In I/R group enriched Prevotellaceae＿Ga6A1＿group,s＿uncultured＿bacterium＿g＿Prevotellaceae＿Ga6A1＿group,that were positively correlated with LPS,TLR4,IL-1β.In JXAM-M group enriched Actinobacteria that was negatively correlated with TNF-α.In JXAM-L group enriched g＿Alloprevotella,s＿uncultured＿bacterium＿g＿Alloprevotella that were negatively positively with TNF-α and IL-6.Conclusion: 1.Professor Hu Jingqing based on the theory of heat retention in blood vessels treated angina pectoris with CHD medication rule.There are 27 flavors of high frequency Chinese medicine,the four qi are mainly warm,slightly cold and calm,the five flavors are mainly sweet,spicy,and bitter,the meridian return are mainly focused on the lungs,heart,and stomach.Based on complex network analysis,the core prescription was based on Si-Miao-Yong-An Decoction,combined with Lianqiao and Huzhang to clear heat and relieve fire,Danshen and Guizhi to promote blood circulation and channel pulse.The whole formula embodied the treatment core of clearing the heat of blood and smoothing the blood stasis of heart pulse.2.JXAM decoction may play a role in the treatment of CHD,such asbeta-sitosterol,quercetin,kaempferol,luteolin,sugiol and so on active ingredients.Can be targeted by interleukins,MPPS,MAPK,NFKBIA,NOS3,MCP-1,ICAM-1,etc,it affects LPS response and NF-κB inflammatory signaling pathways and others.3.JXAM decoction protected myocardium,maintained intestinal mucosal barrier,improved intestinal permeability,inhibited TLR4/NF-κB signaling pathway,reduced intestinal inflammatory expression,decreased the levels of LPS and TNF-α,IL-6,IL-1β,IL-17 A inflammatory factors,may reduce further entry of bacteria and inflammatory factors into the bloodstream to affect the heart.It regulated gut microbiota,and the inflammatory response may be reduced by regulating Prevotellaceae＿Ga6A1＿group,Actinobacteria,Alloprevotella and other inflammatory related bacteria.The effect of JXAM decoction in medium and high dose groups was more significant.