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

  • Psychopharmacology (Berl). 2023 Jul 12. doi: 10.1007/s00213-023-06415-6.
Hanyue Luo  1  2 ,  Caishi Zhang  3 ,  Lujuan He  2 ,  Zefang Lin  2 ,  Ji-Chun Zhang  2 ,  Qi Qi  4 ,  Jia-Xu Chen  5 ,  Wei Yao  6
Affiliations
  • 1. Guangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
  • 2. Department of Physiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
  • 3. School of Pharmacy, Jinan University, Guangzhou, 510632, Guangdong, China.
  • 4. MOE Key Laboratory of Tumor Molecular Biology, Department of Pharmacology, School of Pharmacy, Jinan University, Guangzhou, 510632, China. [email protected].
  • 5. Guangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China. [email protected].
  • 6. Guangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China. [email protected].
PMID: 37436491 DOI: 10.1007/s00213-023-06415-6
Abstract

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.

Keywords
18β-glycyrrhetinic acid; Anti-inflammation; Microglia; Neuroprotection; Parkinson’s disease.
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