Clinical Observation On The Intervention Of Shengui Capsule In Heart Failure With Preserved Ejection Fractio

BackgroundHeart failure with preserved ejection fraction(HFpEF)is an important type of heart failure.The pathology of HFpEF is complex,and current treatments mainly involve using diuretics to reduce volume overload and treating comorbidities.Treatment options are relatively limited,and there is currently no significant improvement in clinical outcomes for HFpEF.The pathology and treatment of HFpEF are still under exploration.Previous studies have shown that traditional Chinese medicine has unique advantages in improving the quality of life and clinical symptoms of patients with HFpEF.Objectives1.To clinically verify the efficacy of Shengui Capsule in treating HFpEF patients with yang deficiency and blood stasis syndrome(Yangxu Xueyu).2.To explore the potential mechanism of Shengui Capsule in treating HFpEF using network pharmacology methods.Methods1.A randomized controlled trial will be conducted.Patients diagnosed with HFpEF and diagnosed with Yang deficiency and blood stasis syndrome who visited Dongzhimen Hospital of Beijing University of Chinese Medicine from April 2022 to December 2022 will be recruited and randomized into the control group and the experimental group according to inclusion and exclusion criteria.The experimental group will receive standardized Western medicine treatment and Shengui Capsule,while the control group will receive standardized Western medicine treatment and placebo(provided by Shanghai Yudan Pharmaceutical Co.,Ltd.,with the same appearance as Shengui Capsule).The treatment will last for 12 weeks.The changes in the Kansas City Cardiomyopathy Questionnaire(KCCQ)scores,TCM syndrome score,and adverse events will be observed before and after treatment in both groups.2.The main chemical components and target proteins of the herbs used in Shengui Capsule will be searched and standardized using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform(TCMSP),and a "herb-active ingredient-target protein" network will be constructed using Cytoscape 3.9.1 software and analyzed topologically.The target proteins related to HFpEF disease will be obtained from databases such as GeneCards,OMIM,TTD,and DrugBank,and a Venn diagram will be used to obtain the common target proteins between the two.The protein interaction network of the common target proteins of the drug-disease will be constructed based on the STRING platform.Gene Ontology(GO)biological function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis will be conducted using the Metascape platform.A"component-target-pathway" network will be constructed using Cytoscape 3.9.1 software and analyzed topologically to explore the important active ingredients and core target proteins of Shengui Capsule in the treatment of HFpEF.Results1.The clinical study included a total of 46 patients,with 4 patients dropping out during the treatment period,leaving 21 patients in the treatment group and 21 patients in the control group.There were no statistically significant differences in baseline data between the two groups of HFpEF patients at enrollment,indicating comparability(P>0.05).Before treatament,there was no statistically significant difference in KCCQ score and TCM syndrome score between the two groups(P>0.05).(1)KCCQ score:The results showed that after intervention,both groups had improved KCCQ scores and scores on each subscale(P<0.05).The KCCQ score and scores for physical limitations,symptom total,quality of life,and social limitations were better in the treatment group than in the control group(P<0.05),with no statistically significant difference in the self-efficacy subscale(P>0.05).(2)TCM syndrome score:The results showed that after intervention,both groups had improved TCM syndrome scores(P<0.05),and the improvement in TCM syndrome score was better in the treatment group than in the control group(P<0.05).(3)Safety:There were no adverse drug reactions or hospitalizations or deaths due to heart failure in either group during the observation and follow-up period.2.After screening,82 active ingredients of Shengui Capsule and 749 corresponding targets were obtained.The targets of HFpEF disease were 2,994,with an intersection of 70 targets between the disease and the drug.GO enrichment analysis identified 1,099 biological processes,53 cellular components,and 86 molecular functions.KEGG pathway enrichment analysis identified 162 pathways,including major Pathways in cancer,Lipid and atherosclerosis,Insulin resistance,and HIF-1,calcium ion,VEGF,AMPK signaling pathways,which were related to the development of atherosclerosis,diabetes,inflammation,fibrosis,cell proliferation,apoptosis,and cell cycle regulation.Network topology analysis identified important active ingredients for the treatment of HFpEF,such as kaempferol,oleic acid,beta-sitosterol,Myricanone,Stigmasterol,ginsenoside rh2,etc.The most important target gene was PTGS2,followed by CHRM2,ADRB2,ADRA1B,MAPK8,MAPK14,TNF,NOS3,and ILlB.Conclusions1.The combination of Shengui Capsule and Western medicine routine treatment is effective in improving the clinical symptoms and quality of life of patients with Yangdeficiency and blood stasis syndrome HFpEF,and has good safety.2.The active ingredients in Shengui Capsule,such as kaempferol,oleic acid,betasitosterol,Myricanone,Stigmasterol,ginsenoside rh2,may regulate key targets such as PTGS2,CHRM2,ADRB2,ADRA1B,MAPK8,MAPK14,etc.to modulate lipid and atherosclerosis,MAPK,Thl7,TNF,HIF-1,IL-17 signaling pathways through antiinflammatory effects,improvement of energy metabolism,endocrine,hemodynamics and other actions to play a therapeutic role in HFpEF.