Therapeutic Targets and Molecular Mechanisms of Calycosin in the Treatment of Depression: Insights From Chronic Mild Stress Animal Models

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-04-22 DOI:10.1111/cns.70353

Guowei Gong, Yaqun Liu, Zhenxia Zhang, Yuzhong Zheng

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Abstract

Background

Depression is a complex psychiatric disorder with limited therapeutic options and various side effects. Calycosin, a bioactive compound derived from Astragalus membranaceus, possesses multiple pharmacological properties. This study aimed to investigate the antidepressant effects of calycosin in chronic mild stress (CMS) animal models of depression and to elucidate its underlying mechanisms.

Methods

The antidepressant effects of calycosin were assessed in vivo using CMS animal models of depression, including the grooming frequency test, sucrose intake test, tail suspension test, and open field test. Neurogenic effects were evaluated by measuring the levels of BDNF, GDNF, and NGF in isolated hippocampus tissues. The hepatoprotective effects were assessed by measuring liver enzyme levels. The molecular mechanisms underlying calycosin's antidepressant effects were explored in vitro using PC12 cells.

Results

Calycosin exhibited potent antidepressant-like activities in CMS animal models of depression. Treatment with calycosin significantly alleviated depressive symptoms and improved neurogenic effects. Additionally, calycosin displayed hepatoprotective effects by modulating liver enzymes in vitro. The antidepressant effects of calycosin are mediated by the stimulation of the TrkB–MEK–Erk1/2–CREB signaling pathway.

Conclusion

In conclusion, calycosin shows promise as a novel therapeutic agent for depression due to its potent antidepressant-like activities and diverse pharmacological properties. Further studies are warranted to elucidate the exact molecular targets of calycosin and to assess its efficacy and safety in clinical settings.

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毛蕊异黄酮治疗抑郁症的靶点和分子机制：来自慢性轻度应激动物模型的见解

背景抑郁症是一种复杂的精神疾病，治疗方法有限，且存在各种副作用。萼萼苷是从黄芪中提取的一种生物活性化合物，具有多种药理特性。本研究旨在探讨萼萼苷在慢性轻度应激（CMS）抑郁症动物模型中的抗抑郁作用，并阐明其潜在机制。方法使用慢性轻度应激抑郁动物模型，包括梳理频率试验、蔗糖摄入试验、尾悬挂试验和空场试验，在体内评估钙黄素的抗抑郁作用。通过测量离体海马组织中 BDNF、GDNF 和 NGF 的水平来评估其神经源效应。保护肝脏的作用通过测量肝酶水平来评估。利用 PC12 细胞在体外探讨了萼苷抗抑郁作用的分子机制。结果萼萼苷在 CMS 抑郁症动物模型中表现出强效抗抑郁样活性。使用萼萼苷治疗可明显缓解抑郁症状，改善神经源效应。此外，萼萼苷还能在体外调节肝酶，显示出保护肝脏的作用。钙黄素的抗抑郁作用是通过刺激TrkB-MEK-Erk1/2-CREB信号通路介导的。结论总之，钙黄素具有强效抗抑郁样活性和多种药理特性，有望成为一种新型抑郁症治疗药物。为阐明钙黄素的确切分子靶点并评估其在临床环境中的有效性和安全性，还需要进一步的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.