Zhang Ying, Yang Lei, Zhang Qiuyu, Li Chao, Mao Fuqiang, Zhuo Chuanjun
Laboratory of Computational Biology and Computational Psychiatry (CBCP-Lab), Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Medical University Affiliated Tianjin Mental Health Center, Tianjin, 300222, China.
Laboratory of Psychiatric-Neuroimaging-Genetic and Co-morbidity (PNGC_Lab), Tianjin Anding Hospital, Tianjin Mental Health Center of Tianjin Medical University, Tianjin, 300222, China.
Transl Psychiatry. 2025 Jun 16;15(1):202. doi: 10.1038/s41398-025-03410-7.
Psilocybin is among the most extensively studied psychedelics, with previous research suggesting its potential therapeutic role in suicide prevention. However, the precise mechanisms through which psilocybin may aid in suicide prevention remain unclear. This study thus employed network pharmacology and molecular docking tools to explore the mechanisms by which psilocybin may contribute to suicide prevention. Relevant drug- and disease-related targets were identified. Overlapping drug- and disease-related targets were extracted from the bioinformatics platform and imported into the STRING database to construct a protein-protein interaction (PPI) network. Key targets were selected based on topological parameters derived from network analyses conducted using Cytoscape 3.10.1. These key targets were further analyzed using GO and KEGG enrichment approaches conducted with the DAVID tool. A drug-disease-target-pathway network was subsequently constructed in Cytoscape 3.10.1. Finally, molecular docking analyses were performed to assess psilocybin's potential to interact with key targets using AutoDock Vina and the PyMOL software. A total of 46 potential targets associated with psilocybin and relevant to suicide treatment were identified, of which 13 were imported into the DAVID tool for enrichment analyses. Network analyses identified four targets-HTR2A, HTR2C, HTR7, and PRKACA-that may serve as therapeutic targets for psilocybin in suicide prevention. Enrichment analysis outcomes suggested that psilocybin may prevent suicide by modulating the serotonergic synapse and calcium signaling pathways. Molecular docking analyses revealed that HTR2A, HTR2C, HTR7, and PRKACA strongly bind to psilocybin. This study provides insights into the molecular mechanisms underlying the potential role of psilocybin in suicide prevention, offering a novel basis for further research.
裸盖菇素是研究最为广泛的迷幻剂之一，先前的研究表明其在预防自杀方面具有潜在的治疗作用。然而，裸盖菇素预防自杀的确切机制仍不清楚。因此，本研究采用网络药理学和分子对接工具来探索裸盖菇素预防自杀的机制。确定了相关的药物和疾病相关靶点。从生物信息学平台提取重叠的药物和疾病相关靶点，并导入STRING数据库以构建蛋白质-蛋白质相互作用（PPI）网络。基于使用Cytoscape 3.10.1进行网络分析得出的拓扑参数选择关键靶点。使用DAVID工具进行的GO和KEGG富集分析对这些关键靶点进行了进一步分析。随后在Cytoscape 3.10.1中构建了药物-疾病-靶点-通路网络。最后，使用AutoDock Vina和PyMOL软件进行分子对接分析，以评估裸盖菇素与关键靶点相互作用的潜力。共确定了46个与裸盖菇素相关且与自杀治疗相关的潜在靶点，其中13个导入DAVID工具进行富集分析。网络分析确定了四个靶点——5-羟色胺受体2A（HTR2A）、5-羟色胺受体2C（HTR2C）、5-羟色胺受体7（HTR7）和蛋白激酶A催化亚基α（PRKACA）——它们可能是裸盖菇素预防自杀的治疗靶点。富集分析结果表明，裸盖菇素可能通过调节5-羟色胺能突触和钙信号通路来预防自杀。分子对接分析表明，HTR2A、HTR2C、HTR7和PRKACA与裸盖菇素强烈结合。本研究为裸盖菇素预防自杀潜在作用的分子机制提供了见解，为进一步研究提供了新的基础。
