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Updated: Feb 22, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
Published on: June 6, 2025
Folic acid exerts antidepressant effects by upregulating brain-derived neurotrophic factor and glutamate receptor 1
Liangcai Gao1, Xinnan Liu, Li Yu
1aDepartment of Biomedical Sciences, School of Life Science, East China Normal University, Shanghai, China bDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Abstract:
Folic acid is a vitamin with a variety of pharmacological effects. The present study aims to explore the beneficial effects of folic acid on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors and its possible mechanisms. The behavioral tests including open-field test, tail suspension test, and forced swimming test were used to evaluate the antidepressant effects of folic acid. Then the changes of brain 5-hydroxytryptamine (5-HT) concentration, brain-derived neurotrophic factor (BDNF), glutamate receptor 1 (GluR1) expression levels, and synaptic organization were assessed to explore the antidepressant mechanisms of folic acid. Our results showed that CUMS caused significant depression-like behaviors, neuropathological changes, and decreased brain 5-HT concentration, BDNF, and GluR1 expression in the hippocampus and association cortex. In conclusion, the results showed that folic acid significantly improved depression-like behaviors in CUMS-induced rats, and its antidepressant effects might be related to the increase of brain 5-HT concentration, BDNF and GluR1 expression, and repair of synaptic organization in the brain.
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