Berberine exerts antidepressant-like effects via regulating miR-34a-synaptotagmin1/Bcl-2 axis
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摘要:
Abstract:
Objective: Berberine, a cationic alkaloid first isolated in 1917, has been approved by the China Drug Administration for decades. Accumulating evidence demonstrated its antidepressant-like activities in vivo. Our previous study has shown that chronic stress leads to the upregulation of miR-34a in the hippocampus of mice. This study aims to evaluate the underlying miR-34a mediated mechanism of berberine in chronic stress-induced depression in mice. Methods: In the present study, mice were administered with berberine during chronic stress. Levels of miR-34a, dendritic density, mitochondrial morphology, and neurogenesis were assessed in the hippocampus. Subsequently, miR-34a agomir was used as a pharmacological intervention for the investigation of berberine. Results: The results showed that berberine reversed the decrease in sucrose preference and the increase in latency to feed without altering total food consumption. Furthermore, chronic stress-induced overexpression of miR-34a decreased synaptotagmin-1 and Bcl-2 levels, thereby impairing spinal morphology, mitochondria and neurogenesis. Berberine inhibited miR-34a expression, in turn restored synaptotagmin-1 and Bcl-2 levels, and thus improved spinal morphology, mitochondria and neurogenesis in the hippocampus. However, the improvements induced by berberine were totally blocked by the pretreatment of miR-34a agomir, which caused the elevation of miR-34a levels in the hippocampus. Conclusion: This finding demonstrated that miR-34a downregulation was involved in the antidepressant-like effects of berberine in mice exposed to chronic stress.
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Funding for this study was provided by the Education Department of Fujian Province [2019-WJ-38], Xiamen Municipal Health Commission [2019-WJ-38]. We would like to thank the Instrumental Analysis Center of Huaqiao University for the help of confocal testing.
Li-tao Yi a, Ji-xiao Zhub, Shu-qi Donga, Min Chena, Cheng-fu Lic. Berberine exerts antidepressant-like effects via regulating miR-34a-synaptotagmin1/Bcl-2 axis[J]. Chinese Herbal Medicines (CHM),2021,13(1):
