Gu Xinyi, Zhang Guanying, Wang Qixue, Song Jing, Li Ying, Xia Chenyi, Zhang Ting, Yang Li, Sun Jijia, Zhou Mingmei
Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Cell Dev Biol. 2022 Aug 5;10:900637. doi: 10.3389/fcell.2022.900637. eCollection 2022.
(Rupr. et Maxim.) Harms (ASH) is a traditional herbal medicine widely known for its antifatigue and antistress effects, as well as tonifying qi, invigorating spleen and kidney, and tranquilizing the mind. Recent evidence suggests that ASH has a therapeutic effect on major depressive disorder (MDD), but its mechanism is still unclear. The current study aimed to investigate the effect of ASH on MDD and potential therapeutic mechanisms. The chemical compound potential target network was predicted based on network pharmacology. Simultaneously, chronic unpredictable mild stress (CUMS) model mice were orally administrated ASH with three dosages (400, 200, and 100 mg/kg) for 6 weeks, and hepatic metabolomics based on gas chromatography-mass spectrometry (GC-MS) was carried out to identify differential metabolites and related metabolic pathways. Next, the integrated analysis of metabolomics and network pharmacology was applied to find the key target. Finally, molecular docking technology was employed to define the combination of the key target and the corresponding compounds. A total of 13 metabolites and four related metabolic pathways were found in metabolomics analysis. From the combined analysis of network pharmacology and metabolomics, six targets (DAO, MAOA, MAOB, GAA, HK1, and PYGM) are the overlapping targets and two metabolic pathways (glycine, serine, and threonine metabolism and starch and sucrose metabolism) are the most related pathways. Finally, DAO, MAOA, MAOB, GAA, HK1, and PYGM were verified bounding well to their corresponding compounds including isofraxidin, eleutheroside B1, eleutheroside C, quercetin, kaempferol, and acacetin. Based on these results, it was implied that the potential mechanism of ASH on MDD was related to the regulation of metabolism of several excitatory amino acids and carbohydrates, as well as the expression of DAO, MAOA, MAOB, GAA, HK1, and PYGM.
（鲁普雷希特和马克西姆）哈姆斯（ASH）是一种传统草药，以其抗疲劳和抗应激作用以及补气、健脾补肾、宁心安神而广为人知。最近的证据表明，ASH对重度抑郁症（MDD）有治疗作用，但其机制仍不清楚。当前的研究旨在探讨ASH对MDD的影响及潜在治疗机制。基于网络药理学预测了化合物潜在靶点网络。同时，将慢性不可预测轻度应激（CUMS）模型小鼠分别口服三种剂量（400、200和100毫克/千克）的ASH，持续6周，并基于气相色谱-质谱联用（GC-MS）进行肝脏代谢组学分析，以鉴定差异代谢物和相关代谢途径。接下来，应用代谢组学和网络药理学的综合分析来寻找关键靶点。最后，采用分子对接技术确定关键靶点与相应化合物的结合情况。代谢组学分析共发现13种代谢物和4条相关代谢途径。通过网络药理学和代谢组学的联合分析，六个靶点（DAO、MAOA、MAOB、GAA、HK1和PYGM）是重叠靶点，两条代谢途径（甘氨酸、丝氨酸和苏氨酸代谢以及淀粉和蔗糖代谢）是最相关的途径。最后，验证了DAO、MAOA、MAOB、GAA、HK1和PYGM与它们相应的化合物（包括异秦皮啶、刺五加苷B1、刺五加苷C、槲皮素、山奈酚和金合欢素）结合良好。基于这些结果，提示ASH对MDD的潜在机制与几种兴奋性氨基酸和碳水化合物的代谢调节以及DAO、MAOA、MAOB、GAA、HK1和PYGM的表达有关。
