Abstract
Presently, the regulatory mechanism underlying depression is indistinct, and almost 50% of depression sufferers undergo no apparent effects during treatment. This study explored the effects of medicarpin on depressive-like behaviors in a chronic unpredictable mild stress (CUMS)-induced mouse model of depression. The results of network pharmacological analysis revealed that liver X receptor β (LXRβ) might be a potential target of medicarpin and depression. The LXRβ level was reduced in the amygdala of mice induced by CUMS; however, this effect was suppressed by co-treatment with medicarpin. Medicarpin treatment ameliorated depressive-like behaviors in CUMS-induced mice by modulating LXRβ level. Moreover, medicarpin treatment reduced M1 polarization and enhanced M2 polarization of amygdala microglia in CUMS-induced mice, as well as increased GFAP level in the amygdala. Medicarpin treatment also suppressed CUMS-induced inflammation and hindered nuclear factor-κ B (NF-κB) signaling activation. These data indicate that medicarpin activated astrocytes and inhibited microglia M1 polarization while promoted M2 polarization by enhancing the expression of LXRβ. Hence, our results suggest that medicarpin could have a positive effect on the treatment of depression, and LXRβ could serve as a novel therapeutic target.
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Funding
This study was funded by National Natural Science Foundation of China (No. 82001422 for Dr. Li) and the Natural Science Foundation of Jiangsu Province for Dr. Li (Grants No BK 20200274).
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We declare that this work was done by the author(s) named in this article and all liabilities pertaining to claims relating to the content of this article will be borne by the authors. YL conceived and designed the study. XH, JZ, and QZ collected the data. XL and GZ analyzed the data. YL wrote the manuscript. All authors read and approved the manuscript for publication.
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Li, Y., He, X., Zhang, J. et al. Medicarpin Improves Depressive-Like Behaviors in a Chronic Unpredictable Mild Stress-Induced Mouse Model of Depression by Upregulating Liver X Receptor β Expression in the Amygdala. Neurotox Res 40, 1937–1947 (2022). https://doi.org/10.1007/s12640-022-00610-7
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DOI: https://doi.org/10.1007/s12640-022-00610-7