基于血清药物化学和网络药理学的方法研究柴胡疏肝散的抗抑郁作用

A Serum Pharmacochemistry and Network Pharmacology-based Approach to Study the Anti-depressant Effect of Chaihu-Shugan San.

作者信息

Deng Man-Fei, Yan Yi-Zhi, Zhu Shan-Shan, Zhou Ke, Tan Si-Jie, Zeng Peng

机构信息

Department of Physiology, School of Basic Medicine, Hengyang Medical School, University of South China, Hengyang, 421001, China.

Department of Histology and Embryology, School of Basic Medicine, Hengyang Medical School, University of South China, Hengyang, 421001, China.

出版信息

Comb Chem High Throughput Screen. 2025;28(3):533-550. doi: 10.2174/0113862073285198240322072301.

DOI:10.2174/0113862073285198240322072301

PMID:38551057

Abstract

AIMS

The aim of this study is to explore the anti-depressant mechanism of Chaihu- Shugan San based on serum medicinal chemistry and network pharmacology methods.

BACKGROUND

Depression lacks effective treatments, with current anti-depressants ineffective in 40% of patients. Chaihu-Shugan San (CHSGS) is a well-known traditional Chinese medicine compound to treat depression. However, the chemical components and the underlying mechanisms targeting the liver and brain in the anti-depressant effects of CHSGS need to be elucidated.

METHODS

The chemical components of CHSGS in most current network pharmacology studies are screened from TCMSP and TCMID databases. In this study, we investigated the mechanism and material basis of soothing the liver and relieving depression in the treatment of depression by CHSGS based on serum pharmacochemistry. The anti-depressant mechanism of CHSGS was further verified by proteomics and high-throughput data.

RESULTS

Through serum medicinal chemistry, we obtained 9 bioactive substances of CHSGS. These ingredients have good human oral bioavailability and are non-toxic. Based on liver ChIPseq data, CHSGS acts on 8 targets specifically localized in the liver, such as FGA, FGB, and FGG. The main contributors to CHSGS soothing the liver qi targets are hesperetin, nobiletin, ferulic acid, naringin and albiflorin. In addition, network pharmacology analysis identified 9 blood components of CHSGS that corresponded to 63 anti-depressant targets in the brain. Among them, nobiletin has the largest number of anti-depressant targets, followed by glycyrrhizic acid, ferulic acid, albiflorin and hesperetin. We also validated the anti-depressant mechanism of CHSGS based on hippocampal proteomics. CHSGS exerts anti-depressant effects on synaptic structure and neuronal function by targeting multiple synapse related proteins.

CONCLUSION

This study not only provides a theoretical basis for further expanding the clinical application of CHSGS, but also provides a series of potential lead compounds for the development of depression drugs.

摘要

目的

本研究旨在基于血清药物化学和网络药理学方法探索柴胡疏肝散的抗抑郁机制。

背景

抑郁症缺乏有效的治疗方法，目前的抗抑郁药对40%的患者无效。柴胡疏肝散（CHSGS）是一种治疗抑郁症的著名中药复方。然而，CHSGS抗抑郁作用中针对肝脏和大脑的化学成分及潜在机制尚需阐明。

方法

当前大多数网络药理学研究中CHSGS的化学成分是从TCMSP和TCMID数据库中筛选的。在本研究中，我们基于血清药物化学研究CHSGS治疗抑郁症时疏肝解郁的机制和物质基础。通过蛋白质组学和高通量数据进一步验证CHSGS的抗抑郁机制。

结果

通过血清药物化学，我们获得了CHSGS的9种生物活性物质。这些成分具有良好的人体口服生物利用度且无毒。基于肝脏ChIPseq数据，CHSGS作用于8个特异性定位于肝脏的靶点，如FGA、FGB和FGG。CHSGS疏肝理气靶点的主要贡献成分是橙皮素、川陈皮素、阿魏酸、柚皮苷和芍药苷。此外，网络药理学分析确定了CHSGS的9种血液成分，它们对应于大脑中的63个抗抑郁靶点。其中，川陈皮素的抗抑郁靶点数量最多，其次是甘草酸、阿魏酸、芍药苷和橙皮素。我们还基于海马蛋白质组学验证了CHSGS的抗抑郁机制。CHSGS通过靶向多种突触相关蛋白对突触结构和神经元功能发挥抗抑郁作用。