Investigating The Effective Components And Mechanism Of Mahuang Fuzi Xixin Decoction In Treating Sick Sinus Syndrome Based On Network Pharmacology

Objective: Based on network pharmacology,this study aims to explore the effective components and mechanism of Mahuang Fuzi Xixin Decoction in the treatment of sick sinus syndrome.Methods:(1)The chemical components and related potential target information of Mahuang Fuzi Xixin Decoction were collected and sorted through the TCMSP database and literature.The Swiss Target Prediction database was used to predict and supplement the components that were not collected.The dataset of chemical components and potential targets of Mahuang Fuzi Xixin Decoction was formed;(2)Sick sinus syndrome related targets were screened from Gene Cards database,and disease target dataset related to sick sinus syndrome was sorted out;(3)Cytoscape software was used to show the relationship between Chinese medicine,chemical components and disease targets,a biological network of "Mahuang Fuzi Xixin Decoction Drug-Chemical Components-Target-Sick Sinus Syndrome" was formed,Cyto NCA topology analysis was performed to obtain the significant components and related targets of Mahuang Fuzi Xixin Decoction in the treatment of sick sinus syndrome;(4)Ledock software was used to perform molecular docking and verify the reliability of binding of key chemical components and core targets;(5)DAVID and Metascape databases were used to perform GO function annotation and KEGG pathway enrichment analysis of target points respectively to predict the mechanism of Mahuang Fuzi Xixin Decoction in the treatment of sick sinus syndrome.Results:(1)Through the analysis of the biological network of Mahuang Fuzi Xixin Decoction on the related targets of sick sinus syndrome,a total of 199 significant components of Mahuang Fuzi Xixin Decoction in the treatment of sick sinus syndrome was predicted,including Rutin,noraconitine,β-asarone;(2)10 key chemical components such as luteolin,quasi-galaconitine and kaempferol,and 10 core targets such as ADRB2,SCN5 A and AR in the network are obtained by topological analysis;(3)The molecular docking confirmed that the 9 core targets except KCNH2 have strong binding activity with key chemical components,which proves the reliability of the key chemical components and core targets;(4)By conducting GO function annotation and KEGG pathway enrichment analysis,it is speculated that the mechanism of Mahuang Fuzi Xixin Decoction in the treatment of SSS may be:(1)regulation of cytokine activity,inhibitation or reversing myocardial fibrosis,and improving the pathological basis of SSS;(2)regulating cells’ response to inflammatory stimuli,hypoxia,and aging,protect cardiomyocytes,reducing the damage of functional units in the sinoatrial node and surrounding tissues;(3)regulating protein activity and cells’ response to mechanical stimuli,inducing expression of plasma membrane receptors,and enhancing The "calcium clock" and "membrane clock" activity of sinoatrial node cells expand blood vessels,promoting normal electrophysiological activities of sinoatrial node cells,improving arrhythmia and the symptoms of hypoperfusion of tissues and organs;(4)affecting related diseases that may lead to SSS,and posing a limitation in multiple diseases inducing and aggravating the occurrence of SSS.Conclusion: Through the network pharmacological analysis and molecular docking verification of Mahuang Fuzi Xixin Decoction in the treatment of sick sinus syndrome,this study preliminarily predicted the significant components and mechanism of action of Mahuang Fuzi Xixin Decoction in the treatment of sick sinus syndrome.It provides theoretical support in molecular biology for the clinical application of Mahuang Fuzi Xixin Decoction,and provides a certain amount of reference information for the in-depth study of the mechanism of action for the treatment of SSS and the secondary development of the compound.