Orally Administered\nGinkgolide C Alleviates MPTP-Induced\nNeurodegeneration by Suppressing Neuroinflammation and Oxidative Stress\nthrough Microbiota–Gut–Brain Axis in Mice

Parkinson’s disease (PD) is a neurodegenerative\ndisease\ncharacterized by the progressive loss of dopaminergic neurons in the\nsubstantia nigra, the etiology of which remains unclear. Studies have\nshown that neuroinflammation and oxidative stress (OS) play an important\nrole in neuronal damage in patients with PD. Disturbances in the gut\nmicrobiota influence neuroinflammation and OS through the microbiota–gut–brain\naxis. Ginkgolide C (GC), a traditional Chinese medicine extracted\nfrom the leaves of Ginkgo biloba, has\nbeen reported to exhibit anti-inflammatory effects and the ability\nto modulate intestinal microbial composition. However, the potential\nof GC to positively impact PD by modulating the gut microbiota remains\nunexplored. This study aimed to explore the effects of GC on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine\n(MPTP)-induced PD in mice and elucidate its underlying mechanisms.\nOur findings elucidated that GC treatment significantly ameliorates\nbehavioral deficits as well as pathological damage via restoring gut\nmicrobial homeostasis to downgrade OS and neuroinflammation in MPTP-induced\nPD mice. Mechanistically, GC treatment exerts antioxidant effects\nvia activating the AKT/Nrf2/HO-1 pathway in MPP<sup>+</sup>-exposed\nSN4741 neuronal cells and significantly downregulates the expression\nof inflammatory mediators via regulating NF-κB and MAPK signaling\nin lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Overall,\nour study demonstrates that GC administration alleviates MPTP-induced\nneurodegeneration via rebuilding gut microbial homeostasis to inhibit\nOS and neuroinflammation in mice, indicating that GC might serve as\na promising candidate medicine for PD.