Icariin prevents depression-like behaviors in chronic unpredictable mild stress-induced rats through Bax/cytoplasm C/caspase-3 axis to alleviate neuronal apoptosis

Abstract

Major depressive disorder (MDD) affects approximately 16% of the global population. Our previous study has demonstrated that icariin (ICA) exhibits anti-depressant activity by increasing the expression of Brain Derived Neurotrophic Factor (BDNF) in a rat model of chronic unpredictable mild stress (CUMS). In this study, we investigated whether and how ICA can prevent CUMS-induced depression-like behaviors in rats by modulating hippocampus neuronal apoptosis. Forty male rats were randomly divided into control, CUMS, CUMS-fluoxetine (Flx) (10 mg/kg), and CUMS-ICA (20 mg/kg) groups. Behavior tests including sucrose preference test (SPT), open field test (OFT), elevated plus-maze (EPM), and forced swimming tests (FST) were performed. The Nissl staining and TUNNEL assay were used to determine neuronal apoptosis. Subsequently, expression of glucocorticoid receptor (GR), Bcl-2, cytochrome C, caspase-3 and Bax in the hippocampus were tested by western blot . Our results show that a chronic administration of ICA (20 mg/kg) can prevent CUMS-induced depressant-like behaviors in male model rats. Additionally, ICA significantly inhibited mitochondrial translocation of GR, reduced mitochondrial outer membrane permeabilization (MOMP) to suppress the release of cytochrome C, and then inhibit the activation of caspase-3. In conclusion, our research provides new evidence to understand the anti-depressant activity of ICA, which relates to its inhibition of neuronal apoptosis in hippocampus through mitochondrial apoptotic pathway.

Therapeutic potential of Erxian decoction and its special chemical markers in depression: a review of clinical and preclinical studies

“…Icariin exerts inhibitory effects on hippocampal apoptosis in the CUMS-induced depression rat model by downregulating the expression levels of Bax, caspase-3, cleaved caspase-3, and cytochrome C and upregulating the expression of Bcl-2 ( Wu et al, 2023 ). Moreover, icariin promotes hippocampal neurogenesis in the CUMS-induced depression rat model as evidenced by the upregulation of the number of precursor neurons and mature neurons.…”

Arginine alleviates Clostridium perfringens α toxin-induced intestinal injury in vivo and in vitro via the SLC38A9/mTORC1 pathway

“…Some family members, like Bcl-2 and Bcl-XL, inhibit apoptosis, whereas others, like Bax, promote cell death ( 40 ). The overexpression of Bax promotes the release of cytochrome C, which subsequently activates the downstream Caspase-3 protease, mediating cell death ( 41 , 42 ). Bcl-2 and Bcl-XL can heterodimerize with Bax and neutralize the effects of the latter ( 43 ).…”

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“…Icariin exerts inhibitory effects on hippocampal apoptosis in the CUMS-induced depression rat model by downregulating the expression levels of Bax, caspase-3, cleaved caspase-3, and cytochrome C and upregulating the expression of Bcl-2 (Wu et al, 2023). Moreover, icariin promotes hippocampal neurogenesis in the CUMS-induced depression rat model as evidenced by the upregulation of the number of precursor neurons and mature neurons.…”