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Ginsenoside Rg2 delays brain aging via inhibiting α-synuclein expression and promoting FoxO-Mediated neurogenesis in
Junjie Zhang1, Jingwen Niu1, Shaojie Yang2
1Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, and Key Laboratory of Molecular Biology (Brain diseases), Anhui University of Chinese Medicine, Hefei, 230012, China; Key Laboratory of Xin'an Medicine, the Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, China.
Ethnopharmacological Relevance:
Panax ginseng C.A. Meyer (ginseng) has been utilized in East Asian medicine for centuries to enhance cognitive function, improve memory, and mitigate age-related decline. Ginsenoside Rg2, a key bioactive saponin from red ginseng, is thought to contribute to its neuroprotective effects on brain health.
Aim Of The Study:
This study aimed to investigate the role of α-synuclein (α-Syn) in brain aging and to elucidate whether ginsenoside Rg2 can delay brain aging by modulating α-Syn expression and promoting FoxO1-mediated neurogenesis in mice.
Materials And Methods:
Naturally aging mice and D-galactose-induced aging mouse models were utilized. α-Syn expression was bi-directionally manipulated in the dentate gyrus (DG) through stereotaxic injection of adeno-associated virus (AAV) for α-Syn overexpression or knockdown. Behavioral tests, immunofluorescence, Western blot, and ELISA were performed to evaluate cognitive function, neurogenesis markers (Ki67, Nestin), aging markers (p53, p21), oxidative stress indicators (MDA, LDH, CAT), and α-Syn expression. Ginsenoside Rg2 was administered to assess its effects.
Results:
α-Syn expression was significantly elevated in the DG of both naturally aging and D-galactose-induced aging mice. Overexpression of α-Syn accelerated brain aging and cognitive decline, whereas knockdown alleviated these effects. Mechanistically, α-Syn overexpression inhibited neurogenesis in the DG via the FoxO1 signaling pathway. Treatment with ginsenoside Rg2 significantly reduced α-Syn expression, decreased oxidative stress and aging markers, enhanced neurogenesis, and improved cognitive function in aging mice.
Conclusions:
This study demonstrates that α-Syn acts as an "accelerator" of brain aging by impairing FoxO1-mediated neurogenesis in the DG. Ginsenoside Rg2 mitigates brain aging and cognitive decline by inhibiting α-Syn expression and promoting neurogenesis, supporting the traditional use of ginseng for cognitive health and aging resilience.
