Exploration of Underlying Mechanisms for Modified Xi-Xin-TangIII in Treating Alzheimer’s Disease through Network Integration Investigation

Abstract Background Chinese natural herbal formula modified Xi-Xin-Tang III (mXXTIII) exhibits therapeutic effects for Alzheimer’s disease(AD). This study aimed to explore the underlying mechanism of mXXTIII for treating AD and discover the main active ingredients and potential drug targets through a combination of network pharmacology-based strategy and molecular docking technique. Methods Single herbs in mXXTIII were screened for active ingredients, and target proteins were predicted. Target screening for AD was performed to establish a disease target database. Subsequently, a protein-protein interaction network was constructed and the correlation between proteins in the network was used to obtain gene clusters, export the subnetwork, and analyze the biological processes facilitated by the targets in this subnetwork. GO and KEGG enrichment analyses of key genes were conducted using the DAVID database. Finally, molecular docking of critical targets and active ingredients was conducted and their interaction patterns were visualized. Results The research received 81 active ingredients, 519 targets, and 3089 disease targets. A total of 264 potential targets of mXXTIII against AD were identified by drawing a Venn diagram and the top action pathways were recognized according to GO and KEGG enrichment analysis. Conclusion Multiple active ingredients, targets, and pathways may be involved in intrinsic molecular actions of mXXTIII in the recovery of AD. The major active ingredients (quercetin, baicalein, formononetin, etc.), critical targets, and key pathways could have played more important roles. The findings may provide a reference for further studies and assessments on the mechanism of resisting AD.