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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1487474
Molecular targets and mechanisms of Sijunzi Decoction in the treatment of Parkinson's disease: evidence from network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation
Provisionally accepted- 1 Hunan University of Chinese Medicine, Changsha, China
- 2 Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Changsha, Anhui Province, China
- 3 School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
- 4 The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
Aim: To explore the molecular mechanism of Sijunzi Decoction (SJZD) in the treatment of Parkinson's disease (PD) through the application of network pharmacology, molecular docking, and molecular dynamics simulations, complemented by experimental verification.The BATMAN-TCM, GeneCards, and DisGeNet databases were searched to screen the active components and therapeutic targets of SJZD. Cytoscape (3.7.1) was used to create a network diagram of the components and targets. The STRING platform was used to construct a proteinprotein interaction (PPI) network. The Bioconductor database and RX64 (4.0.0) software were used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the core target genes. The binding sites and binding energies between SJZD active components and the target were analyzed by molecular docking and dynamic simulation. Finally, the therapeutic effect and mechanism of SJZD were verified by Cell Counting Kit-8 (CCK-8) and Western blotting (WB).Results: This research identified 188 active compounds in SJZD, 1568 drug targets, 2069 PD targets, and 451 intersection targets related to PD. According to network analysis, Adenosine Triphosphate, Tridecanoic Acid, Hexadecanoic Acid, Pentadecanoic Acid, and Adenosine were identified as the core components of SJZD in the treatment of PD. The five targets with the highest Degree values in the PPI network were AKT1, INS, TNF, IL-6, and TP53. The GO and KEGG enrichment analyses, in turn, determined that the administration of SJZD for the treatment of PD may engage processes such as xenobiotic stimulation and biological stimulus response. Furthermore, AGE-RAGE and cAMP signaling pathways related to diabetic complications may be involved. Molecular docking and kinetic simulations showed that IL-6 and AKT1 bind best to Adenosine. Experimental results showed that SJZD significantly reduced 6-OHDA-induced apoptosis of SH•SY5Y cells by activating the PI3K/AKT signaling pathway and regulating the expression of apoptosis factors such as Bcl•2 and Bax.SJZD is essential in the processes of apoptosis and neuronal protection, acting through various components that target multiple pathways. Notably, the PI3K/AKT pathway is a verified SJZD-PD target, providing a reference for clinical precision drug use for PD.
Keywords: Sijunzi decoction, Parkinson's disease, molecular docking, Network Pharmacology, Molecular Dynamics Simulation
Received: 28 Aug 2024; Accepted: 31 Oct 2024.
Copyright: © 2024 Jiang, Wu, Xie, Zhou, Yang, Wu, Xu, Fang and Ge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Rui Fang, Hunan University of Chinese Medicine, Changsha, China
Jinwen Ge, Hunan University of Chinese Medicine, Changsha, China
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