Systematic Evaluation Of The Curative Effect Of Ginkgo Biloba Preparations In The Treatment Of Coronary Heart Disease Complicated With Diabetes And Exploration Of Its Mechanism Of Action

Coronary heart disease(CHD)and diabetes mellitus(diabetes mellitus)are common and frequently occurring clinical diseases in China,with a large number of patients and a rising trend.According to statistics,the prevalence of CHD is 12.3%in the population over 15 years old,and the prevalence of DM in adults is 10.4%.It has been widely recognized that CHD and DM are risk factors for each other.The study shows that the prevalence of DM in CHD inpatients in China is about 52.9%.CHD combined with DM has the characteristics of high incidence rate,high disability rate and high mortality rate,which has great harm to people's health.Therefore,the treatment of CHD combined with DM is still one of the focuses of clinical research.At present,Ginkgo biloba preparation is widely used in the treatment of CHD.According to literature reports and previous studies of the research group,Ginkgo biloba preparation also has a certain clinical efficacy in the treatment of DM.In order to further explore the clinical efficacy and mechanism of Ginkgo biloba preparation in the treatment of CHD combined with DM,the following studies were carried out.Objective1.Based on the methods of bibliometrics and visual analysis,understand the current research status of Chinese and Western medicine in the treatment of CHD combined with DM,grasp the research hotspots,and predict the future research trends.2.To provide evidence-based medical evidence for the safety and effectiveness of Ginkgo biloba preparations in the treatment of CHD and DM based on the systematic evaluation method,and to preliminarily explore the potential of Ginkgo biloba preparations in the treatment of CHD combined with DM.3.Explore the mechanism of Ginkgo biloba leaves preparation in the treatment of CHD combined with DM based on network pharmacology.MethodPart ? Literature Study1.Literature Metrology and Visualization Analysis of Chinese and Western Medicine inTreating Coronary Heart Disease with Diabetes Mellitus1.1 Literature Metrology and Visualization Analysis of TCM Treatment of Coronary Heart Disease with Diabetes MellitusWith the keywords of "coronary heart disease and diabetes mellitus","traditional Chinese medicine","traditional Chinese medicine" and so on,the research on the treatment of CHD combined with DM by traditional Chinese medicine included in China National Knowledge Network(CNKI)was retrieved,and the literature obtained by the above retrieval methods was visually analyzed using CiteSpace 5.1.R6 software.In order to understand the current situation of TCM treatment in detail,the study on the treatment of CHD combined with DM by TCM in the past three years was carried out to make further statistical analysis from the aspects of dosage forms,prescriptions and efficacy indicators.1.2 Literature Metrology and Visualization Analysis of Western Medicine in Treating Coronary Heart Disease with Diabetes MellitusDocuments included in Web of Science database have higher academic value and can more represent the international trend of discipline development.In this study,Web of Science is used as the retrieval database,and "Coronary Heart Disease" and "Diabetes" are used as the subject words to retrieve the research on CHD merged DM collected in Web of Science database in recent ten years.CiteSpace 5.1.R6 software is used for visual analysis.2?Systematic evaluation of Ginkgo biloba preparation in the treatment of coronary heart disease and diabetes mellitus2.1 Overview of the effectiveness and safety of Ginkgo biloba preparations in the treatment of Coronary Heart DiseaseSystematic reviews of Ginkgo biloba preparations for CHD in Chinese and foreign databases were retrieved with the keywords of "Ginkgo biloba leaf","coronary heart disease","Meta","systematic evaluation".Literature screening and data extraction were carried out according to the pre-established inclusion criteria.Methodology and evidence grade evaluation of the included literature were carried out using AMSTAR2 scale and GARDEprofiler software.2.2Meta-analysis of the efficacy and safety of Ginkgo biloba preparations in the treatment of Diabetes MellitusRandomized Controlled Trial(RCT)of Ginkgo biloba preparations in the treatment of DM was retrieved from Chinese and foreign databases with the keywords of "diabetes mellitus","Ginkgo biloba leaves","Ginkgo biloba leaf extract" and so on.Literature screening and data extraction were carried out according to the pre-established exclusion criteria,Jadad scale was used to evaluate the quality of the included literature,and Revman5.3 software was used to meta-analyze the efficacy indicators such as fasting blood glucose,postprandial blood glucose,glycated hemoglobin,adverse reactions,etc.to evaluate the safety and effectiveness of Ginkgo biloba preparations in the treatment of DM.Part ? Mechanism ResearchStudy on the Mechanism of Ginkgo biloba Leaf Preparation in the Treatment of Coronary Heart Disease with Diabetes MellitusTo explore the mechanism of Ginkgo biloba leaves preparation in the treatment of CHD combined with DM based on network pharmacology.The active components of Ginkgo biloba leaves were obtained and screened by searching TCM Systematic Pharmacology Database and Analysis Platform(TCMSP).The databases of Therapeutic Target Database,GAD and Drug bank were retrieved to obtain the disease-related targets of CHD and DM,and the common targets of ginkgo leaf active ingredients and diseases were screened to construct protein interaction network.GO enrichment and KEGG pathway analysis were performed on key targets using Cluo go software.RESULTSPart ? Literature Study1.Literature Metrology and Visualization Analysis of Chinese and Western Medicine in Treating Coronary Heart Disease with Diabetes Mellitus1.1 Literature Metrology and Visualization Analysis of TCM Treatment of Coronary Heart Disease with Diabetes MellitusA total of 587 articles were retrieved.The research in this field is more in-depth,and Ni Qing researchers have the highest volume of papers.Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,has the largest number of publications.At present,research focuses on clinical efficacy,TCM syndromes,etc.The future research direction is to study the mechanism of TCM in the treatment of CHD combined with DM.There are 38 literatures on TCM treatment of CHD combined with DM in recent three years.The treatment methods are mainly decoction treatment(35 articles),followed by Chinese patent medicine(2 articles),injection(2 articles),acupuncture treatment(1 article),involving 41 evaluation indicators of efficacy.The most common types of symptoms are Qi-Yin Deficiency combined with blood stasis and phlegm turbidity and internal obstruction.Activating blood circulation,expectorating phlegm,tonifying qi and nourishing Yin are the main treatment methods.1.2 Literature Metrology and Visualization Analysis of Western Medicine in Treating Coronary Heart Disease with Diabetes Mellitus17,265 studies were finally included.The top 5 countries in volume are the United States,England,China,Italy and Germany.Grundy SM,Ridker PM researchers have the largest number of papers and the highest centrality,which is the academic core in this field.Research focuses on the prevention and treatment of risk factors related to this disease.Future research tends to use evidence-based medicine to find the basis for clinical decision-making.2?Systematic evaluation of Ginkgo biloba preparation in the treatment of coronary heart disease and diabetes mellitus2.1Overviews of the effectiveness and safety of Ginkgo biloba preparations in the treatment of coronary heart diseaseThis study finally included 7 systematic reviews/meta-analysis studies,including 2 English studies and 5 Chinese literature.AMSTAR2 was used to evaluate the methodological quality of the included literature,and the results indicated that the overall quality of the research was low.The GRADEprofiler was used to evaluate the level of evidence in the included literature,and the results suggested that the quality of evidence was low or very low.2.2 Meta-analysis of the efficacy and safety of Ginkgo biloba preparations in the treatment of diabetes mellitusFive studies were included in this study,including two in Chinese and three in English.A total of 257 participants were included in the study.The course of DM is 1-8 years and the treatment period is 15 days-18 months.The type of preparation includes tablets and injections.The overall quality of the literature is general.The results of meta-analysis suggested that the improvement of FPG was better in Ginkgo biloba preparations combined with western medicine or in control group when Ginkgo biloba preparations were added on the basis of treatment.The difference was statistically significant.(MD=-1.47 95%Cl[-2.19.-0.75]P<0.0001);Ginkgo biloba leaves preparation combined with western medicine or control group added with Ginkgo biloba leaves preparation,the improvement of PBG was better than control group.The difference was statistically significant.(MD=-2.48 95%Cl[-3.36,-1.59]P<0.0001);Ginkgo biloba leaves preparation combined with western medicine or control group added with Ginkgo biloba leaves preparation,HbA1C improvement was better than control group,the difference was statistically significant.(MD=-0.37 95%Cl=[-0.74,-0.01]P=0.05).Part ? Mechanisms StudyStudy on the Mechanism of Ginkgo biloba Leaf Preparation in the Treatment of Coronary Heart Disease with Diabetes MellitusIn this study,27 active components and 247 targets of Ginkgo biloba leaves were retrieved.There are 255 CHD disease targets,800 DM disease targets,and 97 common disease targets between CHD and DM.Ginkgo biloba leaves can act on 29 common targets of CHD and DM,which are potential targets of Ginkgo biloba leaves in the treatment of CHD combined with DM.The key targets include:IL6,NOS3,TNF,TP53,PTGS2,IL1B,VEGFA,PPARG,CRP,etc.Through GO and KEGG pathway enrichment analysis,we found that the biological processes of Ginkgo biloba on CHD combined with DM were mainly regulation of acute inflammatory response,negative regulation of lipid storage,and regulation of neuroinflammatory response.The main signaling pathways of Ginkgo biloba leaves in the treatment of CHD combined with DM are:VEGF signaling pathway,AGE-RAGE signaling pathway,etc.ConclusionPart ? Literature Study1.Literature Metrology and Visualization Analysis of Chinese and Western Medicine in Treating Coronary Heart Disease with Diabetes MellitusThrough literature research,it is found that more and more traditional Chinese medicine is used in the treatment of CHD combined with DM,and has certain clinical efficacy,but there are still problems such as low quality of literature,different efficacy indicators,and lack of reliable evidence-based medicine evidence.Western medicine treatment mostly uses the combined treatment of lipid-lowering,glucose-lowering,anticoagulant and other drugs.The amount of drugs taken is large.The side effects of long-term application of drugs and the adverse reactions caused by the interaction of multiple drugs are difficult to avoid.Searching for an economical,effective and safe drug that benefits both CHD and DM is still the focus of current research.2?Systematic evaluation of Ginkgo biloba preparation in the treatment of coronary heart disease and diabetes mellitus2.1 Overviews of Ginkgo biloba preparations in the treatment of coronary heart diseaseThis study shows that Ginkgo biloba leaves preparation can effectively improve the blood lipid level,clinical symptoms,electrocardiogram and other related indicators in CHD patients,with good safety.However,due to the small number and low quality of the included studies,it has limited value in guiding clinical treatment,and further clinical verification and mechanism research are needed.2.2Meta-analysis of the efficacy and safety of Ginkgo biloba preparations in the treatment of diabetes mellitusIn this study,the effectiveness and safety of Ginkgo biloba preparations in the treatment of DM were evaluated by systematic evaluation.Ginkgo biloba preparations combined with basic Western medicine treatment can effectively reduce the levels of FPG,FBG,HbA1C compared with the control group,with fewer adverse reactions and better safety.However,fewer studies were included,the follow-up time was short,and the long-term efficacy and safety were still uncertain,which still needed to be further verified by high-quality clinical studies.Part ? Mechanisms StudyStudy on the Mechanism of Ginkgo biloba Leaf Preparation in the Treatment of Coronary Heart Disease with Diabetes MellitusQuercetin,catechin,sesamin and other active components in Ginkgo biloba leaves are important components in the treatment of CHD combined with DM.Ginkgo biloba leaves regulate the expression of NOS3 and VEGF and inhibit the expression of inflammatory factors such as IL-6 and IL-lbeta through three signaling pathways:VEGF,AGE-RAGE.To achieve the purpose of treating CHD combined with DM.In summary,the study using bibliometrics and evidence-based medicine proves that Ginkgo biloba preparations have certain clinical value for the treatment of CHD combined with DM.The target and mechanism of Ginkgo biloba preparations in the treatment of CHD combined with DM were further preliminarily explored based on network pharmacology.It provides a certain theoretical basis for its clinical application,which still needs further proof by experimental and clinical studies in the future.