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

Autor: Yujiao Li, Xiaolu He, Jieyu Zhang, Qing Zhou, Xuejiao Liu, Guohua Zhou
Rok vydání: 2022
Předmět:
Zdroj: Neurotoxicity research. 40(6)
ISSN: 1476-3524
Popis: 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.
Databáze: OpenAIRE
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