Ginkgo biloba protects striatal neurodegeneration and gut phagoinflammatory damage in rotenone-induced mice model of Parkinson's disease: Role of executioner caspase-3/Nrf2/ARE signaling.

Asymptomatic and early clinical stages of Parkinson's disease (PD) have been linked with comorbid non-motor symptoms including dysfunction of the gastrointestinal (GI) tract. Notwithstanding, neuroprotective and gastroprotective effects of Ginkgo biloba supplements (GBS) have been investigated independently. Hence, whether GBS-mediated GIT-protective capacity could be helpful in PD via gut-brain anti-inflammatory signaling still remains unknown. Treatment with GBS significantly repressed the motor behavioral and neuromuscular deficits and prevented loss of striatal dopaminergic loss by improving the level of tyrosine hydroxylase enzyme and suppressing synucleinopathy development. Striatal neurons and ileal epithelial injury following intraperitoneal rotenone administration were accompanied with oxidoinflammatory/nitroinflammatory stress and marked inhibition of cholinergic transmission. Moreover, there was increased striatal executioner caspase-3 and decreased nuclear factor erythroid-2-related factor 2 (Nrf2) immunoexpression, loss of striatal pyramidal neuron with a marked decrease in length and width of the dendritic spines as well as significant hyperplasia of cryptal cells in the ileal epithelial tissues, all which were reversed by the pretreatment + concurrent (Pre-CONC) and concurrent (CONC) GBS treatment pattern. In sum, we proved the potential dual effects of GBS in preventing both dopaminergic neural-related impairments and gut wall abnormalities linked with PD.