Verbascoside是几种药用植物中发现的一种天然水溶性苯乙酸甙类化合物。它具有广泛的药理作用，包括抗氧化和抗肿瘤作用，并对抗抑郁症具有广泛的治疗效果。在本综述中，我们对初级临床和有限的临床证据进行了评估，全面讨论了Verbascoside的抗抑郁能力及其整体特性，以更好地管理体内和体外模型中的抑郁症，以及它的毒性和药用价值。本综述是根据首选报告项目的系统综述和荟萃分析（PRISMA）编写的。通过对截至2023年4月发表的32项初级临床试验进行系统综述，结合全面的生物信息学分析，包括网络药理学和分子对接，以阐明Verbascoside的抗抑郁作用机制。系统综述的研究来自7个电子数据库：PubMed，Scopus，Web of Science，Cochrane，ResearchGate，ScienceDirect和Google Scholar。研究Verbascoside的抗抑郁作用显示，其具有多种药理机制和途径，例如调节单胺神经递质水平，抑制下丘脑-垂体-肾上腺皮质（HPA）轴过度功能和促进神经保护等过程可能参与其对抗抑郁的作用。Verbascoside通过促进酪氨酸羟化酶mRNA和蛋白质表达，上调5-羟色胺受体1B（5-HT1B）、卓越蛋白、微管相关蛋白2（MAP2）、血红素加氧酶1（HO-1）、SQSTM1、重组自噬相关蛋白5（ATG5）和Beclin-1的表达，并降低caspase-3和a-突触核蛋白的表达，从而发挥抗抑郁作用。我们确定了七个潜在的分子生物学位点（CCL2、FOS、GABARAPL1、CA9、TYR、CA12和SQSTM1）和三个信号通路（谷胱甘肽代谢、细胞色素P450代谢外源物质、流体剪切力和动脉粥样硬化）作为Verbascoside的潜在分子生物学位点。这些发现提供了Verbascoside通过多种药理机制发挥抗抑郁作用的有力证据。然而，进一步的多中心临床病例对照和分子靶向渔获研究需要验证Verbascoside的临床疗效及其底层直接靶点。版权所有©2023年Elsevier GmbH。保留所有权利。

Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative and antineoplastic actions, and a wide range of therapeutic effects against depression.In this review, we appraised preclinical and limited clinical evidence to fully discuss the anti-depression capacity of verbascoside and its holistic characteristics that can contribute to better management of depression in vivo and in vitro models, as well as, its toxicities and medicinal value.This review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic review of 32 preclinical trials published up to April 2023, combined with a comprehensive bioinformatics analysis of network pharmacology and molecular docking, was conducted to elucidate the antidepressant mechanism of action of verbascoside. Studies included in the systematic review were obtained from 7 electronic databases: PubMed, Scopus, Web of Science, Cochrane, ResearchGate, ScienceDirect, and Google Scholar.Studies on the antidepressant effects of verbascoside showed that various pharmacological mechanisms and pathways, such as modulating the levels of monoamine neurotransmitters, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperfunction and promoting neuroprotection may be involved in the process of its action against depression. Verbascoside promotes dopamine (DA) biosynthesis by promoting the expression of tyrosine hydroxylase mRNA and protein, upregulates the expression of 5-hydroxytryptamine receptor 1B (5-HT1B), prominence protein, microtubule-associated protein 2 (MAP2), hemeoxygenase-1 (HO-1), SQSTM1, Recombinant Autophagy Related Protein 5 (ATG5) and Beclin-1, and decreases the expression of caspase-3 and a-synuclein, thus exerting antidepressant effects. We identified seven targets (CCL2, FOS, GABARAPL1, CA9, TYR, CA12, and SQSTM1) and three signaling pathways (glutathione metabolism, metabolism of xenobiotics by cytochrome P450, fluid shear stress and atherosclerosis) as potential molecular biological sites for verbascoside.These findings provide strong evidence that verbascoside exerts its antidepressant effects through various pharmacological mechanisms. However, further multicentre clinical case-control and molecularly targeted fishing studies are required to confirm the clinical efficacy of verbascoside and its underlying direct targets.Copyright © 2023 Elsevier GmbH. All rights reserved.