Revealing the Mechanisms of Byu dMar 25 in the Treatment of Alzheimer's Disease through Network Pharmacology, Molecular Docking, and In Vivo Experiment

Yikuan Du; Jinyan Guo; Yuqi Zhou; Simin Yan; Bijun Xu; Yuni Wang; Duoduo Lu; Zhendong Ma; Qianwen Chen; Qibin Tang; Weichui Zhang; Jinfeng Zhu; Yixing Huang; Chun Yang

doi:10.1021/acsomega.3c01683

Revealing the Mechanisms of Byu dMar 25 in the Treatment of Alzheimer's Disease through Network Pharmacology, Molecular Docking, and In Vivo Experiment

ACS Omega. 2023 Jun 13;8(28):25066-25080. doi: 10.1021/acsomega.3c01683. eCollection 2023 Jul 18.

Authors

Yikuan Du¹, Jinyan Guo^{2

3}, Yuqi Zhou^{2

3}, Simin Yan^{2

3}, Bijun Xu^{2

3}, Yuni Wang^{2

3}, Duoduo Lu^{2

3}, Zhendong Ma^{2

3}, Qianwen Chen^{2

3}, Qibin Tang^{2

3}, Weichui Zhang^{2

3}, Jinfeng Zhu^{2

3}, Yixing Huang^{2

3}, Chun Yang^{2

3}

Affiliations

¹ Central Laboratory, The Tenth Affiliated Hospital of Southern Medical University, Dongguan 523059, China.
² Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523000, China.
³ Dongguan Key Laboratory of stem cell and regenerative tissue engineering, Guangdong Medical University, Dongguan 523808, China.

Abstract

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease, severely reducing the cognitive level and life quality of patients. Byu dMar 25 (BM25) has been proved to have a therapeutic effect on AD. However, the pharmacological mechanism is still unclear. Therefore, this study aims to reveal the potential mechanism of BM25 affecting AD from the perspective of network pharmacology and experimental validation.

Methods: The potential active ingredients of BM25 were obtained from the TCMSP database and literature. Possible targets were predicted using SwissTargetPrediction tools. AD-related genes were identified by using GeneCards, OMIM, DisGeNET, and Drugbank databases. The candidate genes were obtained by extraction of the intersection network. Additionally, the "drug-target-disease" network was constructed by Cytoscape 3.7.2 for visualization. The PPI network was constructed by the STRING database, and the core network modules were filtered by Cytoscape 3.7.2. Enrichment analysis of GO and KEGG was carried out in the Metascape platform. Ledock software was used to dock the critical components with the core target. Furthermore, protein levels were evaluated by immunohistochemistry.

Results: In this study, 112 active components, 1112 disease candidate genes, 3084 GO functions, and 277 KEGG pathways were obtained. Molecular docking showed that the effective components of BM25 in treating AD were β-asarone and hydroxysafflor yellow A. The most important targets were APP, PIK3R1, and PIK3CA. Enrichment analysis indicated that the Golgi genetic regulation, peroxidase activity regulation, phosphatidylinositol 3-kinase complex IA, 5-hydroxytryptamine receptor complexes, cancer pathways, and neuroactive ligand-receptor interactions played vital roles against AD. The rat experiment verified that BM25 affected PI3K-Akt pathway activation in AD.

Conclusions: This study reveals the mechanism of BM25 in treating AD with network pharmacology, which provides a foundation for further study on the molecular mechanism of AD treatment.