18β-glycyrrhetinic acid ameliorates MPTP-induced neurotoxicity in mice through activation of microglial anti-inflammatory phenotype.

Autor: Luo, Hanyue, Zhang, Caishi, He, Lujuan, Lin, Zefang, Zhang, Ji-chun, Qi, Qi, Chen, Jia-xu, Yao, Wei
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Zdroj: Psychopharmacology; Sep2023, Vol. 240 Issue 9, p1947-1961, 15p, 5 Color Photographs, 2 Graphs
Abstrakt: Rationale: 18β-glycyrrhetinic acid (18β-GA) has been reported to have anti-inflammatory and neuroprotective effects. However, the therapeutic effect of 18β-GA in Parkinson's disease (PD) has not been defined. Objective: The current study aimed to evaluate the potential therapeutic effects of 18β-GA in treating PD by mitigating 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Results: The study showed that 18β-GA has anti-inflammatory effects by upregulating TREM2 expression in BV2 cells, which correlates with the presence of NF-E2-related factor-2 (Nrf2). 18β-GA reduced inflammation in BV2 cells treated with 1-methyl-4- phenylpyridinium (MPP+) by enhancing TREM2 expression, which promotes an anti-inflammatory microglial phenotype. Repeated administration of 18β-GA in MPTP-treated mice led to therapeutic effects by enhancing TREM2 expression, resulting in the activation of anti-inflammatory microglia. Moreover, 18β-GA attenuated the decrease in brain-derived neurotrophic factor (BDNF) levels in both MPP+-induced BV2 cells and MPTP-intoxicated mice, indicating the involvement of BDNF in the beneficial effects of 18β-GA. Conclusions: It is probable that activating microglial anti-inflammatory response through TREM2 expression might serve as a novel therapeutic strategy for PD. Additionally, 18β-GA seems to hold potential as a new therapeutic agent for PD. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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