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Ginsenoside Re Inhibits NLRP3 Inflammasome Activation in Depressive Mice by Promoting PINK1-Mediated Mitophagy
Shan Liu1, Yue Zhang2, Hao Zhou2
1Department of Physiology, School of Basic Medical Science, Bengbu Medical University, 2600 Donghai Avenue, Bengbu, Anhui 233000, China.
Abstract:
Ginsenoside Re (Re) was proved effective in improving depressive-like behaviors. However, the potential antidepressant mechanism of Re remains unrevealed. In this study, we investigated whether PINK1-mediated mitophagy and NLRP3 inflammasomes were linked to the antidepressant mechanism of Re in chronic unpredictable mild stress (CUMS) mice and lipopolysaccharide (LPS)-stimulated astrocytes. RNA sequencing and bioinformatics analyses were performed to discover the targets and pathways associated with Re. PTEN-induced putative kinase 1 (PINK1) knockdown was conducted to clarify the role of PINK1-mediated mitophagy in the antidepressant mechanism of Re. The outcomes showed that Re ameliorated depressive-like behaviors, activated PINK1-mediated mitophagy, and inhibited NLRP3 inflammasome activation. PINK1 knockdown attenuated the antidepressant effect of Re. The promotion of mitophagy and the decline of NLRP3 inflammasome activation caused by Re were reversed by PINK1 knockdown. In conclusion, Re inhibited NLRP3 inflammasome activation by promoting PINK1-mediated mitophagy to exert its antidepressant effect.
Insights
Ginsenoside Re improves depression by enhancing mitophagy via PINK1 and reducing NLRP3 inflammasome activation. This study reveals a key mechanism for its antidepressant effects.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Ginsenoside Re (Re) shows antidepressant potential, but its mechanism is unclear.
- Depression is linked to neuroinflammation and mitochondrial dysfunction.
Purpose of the Study:
- To investigate the antidepressant mechanism of Ginsenoside Re.
- To explore the roles of PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy and NLRP3 inflammasomes in Re's effects.
Main Methods:
- Chronic unpredictable mild stress (CUMS) mouse model and lipopolysaccharide (LPS)-stimulated astrocytes were used.
- RNA sequencing, bioinformatics analysis, and PINK1 knockdown were performed.
Main Results:
- Ginsenoside Re ameliorated depressive-like behaviors in CUMS mice.
- Re activated PINK1-mediated mitophagy and inhibited NLRP3 inflammasome activation in astrocytes.
- PINK1 knockdown reversed the antidepressant effects of Re and its impact on mitophagy and inflammasomes.
Conclusions:
- Ginsenoside Re exerts antidepressant effects by promoting PINK1-mediated mitophagy.
- This process subsequently inhibits NLRP3 inflammasome activation, offering a novel therapeutic target.
