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Mahonia Alkaloids (MA) Ameliorate Depression Induced Gap Junction Dysfunction by miR-205/Cx43 Axis

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Abstract

Depression has become an important disease threatening human health. In recent years, the efficacy of Traditional Chinese Medicine (TCM) in treating the disease has become increasingly prominent, so it is meaningful to find new antidepressant TCM. Mahonia fortune (Lindl.) Fedde is a primary drug in traditional formulas for the treatment of depression, and alkaloids are the main components of it. However, the detailed mechanism of Mahonia alkaloids (MA) on depression remains unclear. This study aimed to investigate the effect of MA on gap junction function in depression via the miR-205/Cx43 axis. The antidepressant effects of MA were observed by a rat model of reserpine-induced depression and a model of corticosterone (CORT)-induced astrocytes. The concentrations of neurotransmitters were measured by ELISA, the expression of Connexin 43 (Cx43) protein was measured by Immunohistochemistry and western-blot, brain derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB) proteins were measured by western-blot, the pathological changes of prefrontal cortex were observed by hematoxylin–eosin (H&E) staining. Luciferase reporter assay was performed to verify the binding of miR-205 and Cx43. The regulation effect of Cx43 on CREB was verified by interference experiment. Gap junction dysfunction was detected by fluorescent yellow staining. The results confirmed that MA remarkably decreased miR-205 expression and increased Cx43, BDNF, CREB expression in depression rat and CORT-induced astrocytes. In addition, after overexpression of miR-205 in vitro, the decreased expression of Cx43, BDNF and CREB could be reversed by MA. Moreover, after interfering with Cx43, the decreased expression of CREB and BDNF could be reversed by MA. Thus, MA may ameliorate depressive behavior through CREB/BDNF pathway regulated by miR-205/Cx43 axis.

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Funding

This research was funded in part by National Natural Science Foundation of China (Grant No. 82260776, 81960729), Guangxi Traditional Chinese Medicine Key Discipline Construction Project (GZXK-Z-20–75), Guangxi Natural Science Foundation Project (2022GXNSFBA035505), the State Key Laboratory of Bioactive Substance and Function of Natural Medicines (Open Fund Project No.GTZK202209) and the Key Laboratory Project of Quality Standards of TCM in Guangxi (201902).

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Author notes

  1. Junhui He, Dongmei Li and Jie Wei have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Key Laboratory of Quality Standards, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, China

    Junhui He, Dongmei Li, Jie Wei, Fei He, Dongmei Wei, Yi Li, Jiaxiu Xie, Kedao Lai & Guining Wei

  2. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China

    Shifeng Chu, Zhao Zhang, Naihong Chen & Guining Wei

  3. The Center for Scientific Research of Anhui Medical University, Hefei, 230032, Anhui, China

    Sheng Wang

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  1. Junhui He
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Contributions

GN, NH, JH and DM designed all the experiments. JH, DM and J were responsible for the experiments, the analyses of data, and the first draft of the article. SF, Z, F, DM Wei, JX and Y assisted with the execution of the experiments. NH, GN, DM and KD assisted with the improvement of the article.

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Correspondence to Naihong Chen or Guining Wei.

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He, J., Li, D., Wei, J. et al. Mahonia Alkaloids (MA) Ameliorate Depression Induced Gap Junction Dysfunction by miR-205/Cx43 Axis. Neurochem Res 47, 3761–3776 (2022). https://doi.org/10.1007/s11064-022-03761-3

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