Heliyon
·
2023
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IF 4
Chuan Jiang,Chaonan Wang,Weizhong Qu,Yuanyuan Wang,Hua Wang,Xin Wei,Mingyan Wang,Qianqian He,Yihan Wang,Lirong Yuan,Yonggang Gao
Depression is a complex and prevalent mental illness. Cherry leaf is a traditional Chinese herbal medicine, which has confirmed to exert a certain antidepressant effect, but its potential neural regulation mechanism is not clear. This paper aims to investigate the improved action of cherry leaf decoction (CLD) on chronic unpredictable mild stress (CUMS) rats and its potential neural regulation mechanism by verifying the role and function of NMDAR regulatory target α2δ-1 in depression due to CUMS. Male SD rats were subjected to random stressors persisting for 5 weeks to establish the CUMS depression rat model. CLD could effectively alleviate depression-like behaviors of CUMS rats in behavioral tests including sucrose preference test, forced swimming test, tail suspension test and open field test. After the administration of the CLD, the expression of corticotropic-releasing hormone (CRH) in the hypothalamus was inhibited. Moreover, the levels of CRH, adrenal cortical hormone (ACTH) and corticosterone (CORT) in serum also decreased significantly. CUMS upregulated the expressions of α2δ-1, N-methyl- d -aspartate receptor 1 (NR1), NR2A and NR2B, and enhanced the binding ability to of α2δ-1 and NR1, which were reversed by CLD. The results demonstrated that CLD could ameliorate depression-like behaviors due to CUMS, which was related to the fact that CLD down-regulated α2δ-1 level and interfered with α2δ-1 binding to NR1, thereby reducing NMDAR expression and ultimately inhibiting HPA axis activity.
研究领域:
神经科学
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中药学
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精神医学
✓ 已验证
DOI
高影响因子
CNS Neuroscience & Therapeutics
·
2024
·
IF 4.8
Mingyan Wang,Xin Wei,Yugai Jia,Chaonan Wang,Xinliu Wang,Xin Zhang,Depei Li,Yuanyuan Wang,Yonggang Gao
Background Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Chronic unpredictable mild stress (CUMS) can lead to a significant acceleration of depression development. Quercetin (Que) is a flavonoid compound with a wide range of pharmacological effects. Recent studies have shown that quercetin can improve CUMS‐induced depression‐like behavior, but the mechanism of its improvement is still unclear. α2δ‐1 is a regulatory subunit of voltage‐gated calcium channel, which can interact with N‐methyl‐D‐aspartate receptor (NMDAR) to form a complex. Objective In this study, we found that Que could inhibit the increase of α2δ‐1 and NMDAR expression in rat hypothalamus induced by CUMS. In pain, chronic hypertension and other studies have shown that α2δ‐1 interacts with the NMDAR to form a complex, which subsequently affects the expression level of NMDAR. Consequently, the present study aimed to investigate the antidepressant effect of Que in vivo and in vitro and to explore its mechanism of action in terms of the interaction between α2δ‐1 and NMDAR. Methods Rats were randomly exposed to two stressors every day for 4 weeks to establish a CUMS rat model, then sucrose preference test (SPT), forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were performed to detect the behavior of CUMS rats, so as to evaluate whether the CUMS rat model was successfully established and the improvement effect of Que on CUMS‐induced depression‐like behavior in rats. Experimental techniques such as serum enzyme‐linked immunosorbent assay (ELISA), immunofluorescence, Western blot, and co‐immunoprecipitation, as well as in vitro experiments, were used to investigate the mechanisms by which Que exerts its antidepressant effects. Results Behavioral and ELISA test results showed that Que could produce a reduction in the excitability of the hypothalamic–pituitary–adrenal (HPA) axis in CUMS rats and lead to significant improvements in their depressive behavior. Western blot, immunofluorescence, and co‐immunoprecipitation experiments showed that Que produced a decrease in NMDAR1 and α2δ‐1 expression levels and interfered with α2δ‐1 and NMDAR1 binding. In addition, the neural regulation mechanism of Que on antidepressant effect in PC12 cells knocked out α2δ‐1 gene was further verified. Cellular experiments demonstrated that Que led to a reversal of up‐regulation of NMDAR1 and α2δ‐1 expression levels in corticosterone‐injured PC12 cells, while Que had no effects on NMDAR1 expression in PC12 cells with the α2δ‐1 gene knockout. Conclusions Que has a good antidepressant effect and can significantly improve the depression‐like behavior caused by CUMS. It exerts antidepressant effects by inhibiting the expression level of α2δ‐1, interfering with the interaction between α2δ‐1 and NMDAR, and then reducing the excitability of the HPA axis.
研究领域:
神经科学
·
药理学
·
分子生物学
·
行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Shuxian Zang,Ziyun Ban,Lingchen Hou,Yuxuan Zhang,Yuanyuan Wang,Yuanyuan Zhang,Chaonan Wang,Depei Li,Feiyu An,Yuqi Liu,Yunyun Geng,Yonggang Gao
Ethnopharmacological relevance The herbal combination of Bupleurum chinense DC (Chaihu) and Paeonia lactiflora Pall (Baishao), collectively referred to as Chaihu-Baishao (CB), has been historically utilized in traditional Chinese medicine for the treatment of depression. However, the mechanisms underlying its therapeutic benefits have not been clearly defined. Aim of the study This study investigated whether CB alleviates depressive symptoms by modulating the interaction between the voltage-gated calcium channel subunit α2δ-1 and the N-methyl-D-aspartate receptor (NMDAR) subunit NMDAR2B (NR2B), thereby restoring hippocampal synaptic plasticity. Materials and methods In vivo , the chronic social defeat stress (CSDS) mouse model was employed to assess the impact of CB on depression-like behaviors, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, impairments in hippocampal neuronal and synaptic plasticity, as well as the expression and interaction of α2δ-1 and NR2B. In vitro , corticosterone (CORT) was utilized to induce cellular injury. In PC12 cells, the therapeutic effects of CB-containing serum and the α2δ-1 inhibitor gabapentin (GBP) were assessed, focusing on the interaction between α2δ-1 and NR2B, as well as the expression levels of synaptic proteins postsynaptic density protein 95 (PSD95) and synaptophysin (SYN). The role of CB was further corroborated using Cacna2d1 gene knockout cells. Molecular docking techniques were employed to predict the key active components within CB that target α2δ-1 and NR2B, hereby exerting antidepressant effects. Results In vivo studies demonstrated that CB significantly alleviated depression-like behaviors in mice, decreased levels of adrenocorticotropic hormone (ACTH) and CORT. Furthermore, CB relieved structural damage to hippocampal neurons and synapses, downregulated the expression of α2δ-1 and NR2B, inhibited their interaction and restored synaptic protein expression. In vitro experiments revealed that CB mitigated CORT-induced cellular damage, suppressed the α2δ-1-NR2B interaction, and enhanced synaptic proteins expression. Additionally, studies involving GBP treatment and Cacna2d1 -knockout confirmed that α2δ-1 plays a regulatory role in NR2B expression and synaptic plasticity. Molecular docking analyses identified Saikosaponin C, Saikosaponin B4, and Bupleuroside I as potential key components. Conclusion The findings of this study elucidate a novel mechanism through which CB exerts its antidepressant effects, specifically by modulating the α2δ-1-NR2B interaction and restoring of synaptic plasticity within the hippocampus.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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