Chen QingFeng, Li Fan, Yu DanDan, Li Jian, Fang Cong, Zhang Chen
Department of Pharmacy, Jiangxi Province Hospital of Integrated Chinese and Western Medicine, Nanchang, China.
School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China.
Medicine (Baltimore). 2025 Mar 14;104(11):e41826. doi: 10.1097/MD.0000000000041826.
Depressive disorder is a mental disorder characterized by significant and persistent low mood and cognitive impairments such as memory loss. Sojae Semen Praeparatum (SSP), a traditional Chinese medicine capable of dual use in food for medicinal purposes, can significantly reduce the level of inflammatory factors, but it is not clear whether SSP contains a component that produces an ameliorative effect on depressive disorder by acting on the Tryptophan-Kynurenine pathway (TK pathway). This study aimed to explore the material basis and mechanism of action of the TK pathway, combined with raw letter analysis and molecular docking methods. Through database screening, target comparison, Gene Ontology (GO) annotation, protein-protein interaction analysis, molecular docking, and intermolecular force validation. Differential genes of 4588 clinical patients with depression were obtained through database screening, and 29 shared targets, such as the SKI protooncogene and PR domain-containing protein 16, were obtained by comparison with 295 targets in the existing disease database. Gene Ontology Annotation (GO annotation) and protein-protein interaction analysis using Metascape and String platforms revealed that they were mainly involved in biological processes, such as cell morphogenesis involved in neuron differentiation. Using molecular docking and intermolecular force validation, it was found that 10 components of tempeh, including caffeic acid, interacted with tryptophan, kynurenine, and ALG6 targets in the tryptophan-kynurenine signaling pathway through hydrogen bonding, hydrophobic interactions, and electrostatic interactions. It was determined that 10 ingredients, including caffeic acid in SSP, interact with tryptophan, kynurenine, and ALG6 targets through hydrogen bonding and other forces, thus producing relevant therapeutic effects.
抑郁症是一种以显著且持续的情绪低落和认知障碍（如记忆力减退）为特征的精神障碍。中药淡豆豉可药食两用，能显著降低炎症因子水平，但尚不清楚淡豆豉是否含有通过作用于色氨酸 - 犬尿氨酸途径（TK途径）对抑郁症产生改善作用的成分。本研究旨在结合生信分析和分子对接方法，探索TK途径的物质基础和作用机制。通过数据库筛选、靶点比对、基因本体（GO）注释、蛋白质 - 蛋白质相互作用分析、分子对接和分子间作用力验证。通过数据库筛选获得4588例临床抑郁症患者的差异基因，与现有疾病数据库中的295个靶点比对后，得到29个共同靶点，如SKI原癌基因和含PR结构域蛋白16。使用Metascape和String平台进行基因本体注释（GO注释）和蛋白质 - 蛋白质相互作用分析表明，它们主要参与生物过程，如神经元分化所涉及的细胞形态发生。通过分子对接和分子间作用力验证发现，豆豉的10种成分（包括咖啡酸）通过氢键、疏水相互作用和静电相互作用，与色氨酸 - 犬尿氨酸信号通路中的色氨酸、犬尿氨酸和ALG6靶点相互作用。确定淡豆豉中的10种成分（包括咖啡酸）通过氢键等作用力与色氨酸、犬尿氨酸和ALG6靶点相互作用，从而产生相关治疗作用。
