{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:17:31Z","timestamp":1788898651340,"version":"build-2803163510"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>To explore the molecular mechanism of Sijunzi Decoction (SJZD) in the treatment of Parkinson\u2019s disease (PD) through the application of network pharmacology, molecular docking, and molecular dynamics simulations, complemented by experimental verification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 protein-protein 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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2043SY5Y cells by activating the PI3K\/AKT signaling pathway and regulating the expression of apoptosis factors such as Bcl\u20432 and Bax.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1487474","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T15:53:37Z","timestamp":1732636417000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Molecular targets and mechanisms of Sijunzi decoction in the treatment of Parkinson\u2019s disease: evidence from network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation"],"prefix":"10.3389","volume":"15","author":[{"given":"Yang","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanfeng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwen","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.freeradbiomed.2014.06.004","article-title":"Critical cysteines in Akt1 regulate its activity and proteasomal degradation: implications for neurodegenerative diseases","volume":"74","author":"Ahmad","year":"2014","journal-title":"Free Radic. 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