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Neuroprotective effects of Ginkgo biloba dropping pills in Parkinson's disease.

ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disease in the world; however, it lacks effective and safe treatments. Ginkgo biloba dropping pill (GBDP), a unique Chinese G. biloba leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G. biloba extract EGb 761. Using liquid chromatography tandem-mass spectrometry, 46 GBDP constituents were identified. Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761. A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761, whereas EGb 761 had higher levels of organic acids. Moreover, we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. Although similar effects were observed after EGb 761 treatment, the neuroprotective effects were greater after GBDP treatment on several endpoints. In addition, in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP. These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.

SUBMITTER: Yu D

PROVIDER: S-EPMC8116202 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We have previously shown that standardized extracts of Ginkgo biloba (EGb) modulate fear memory formation, which is associated with CREB-1 (mRNA and protein) upregulation in the dorsal hippocampal formation (dHF), in a dose-dependent manner. Here, we employed proteomic analysis to investigate EGb effects on different protein expression patterns in the dHF, which might be involved in the regulation of CREB activity and the synaptic plasticity required for long-term memory (LTM) formation. Adult male Wistar rats were randomly assigned to four groups (n = 6/group) and were submitted to conditioned lick suppression 30 min after vehicle (12% Tween 80) or EGb (0.25, 0.50, and 1.00 g⋅kg-1) administration (p.o). All rats underwent a retention test session 48 h after conditioning. Twenty-four hours after the test session, the rats were euthanized via decapitation, and dHF samples were removed for proteome analysis using two-dimensional polyacrylamide gel electrophoresis, followed by peptide mass fingerprinting. In agreement with our previous data, no differences in the suppression ratios (SRs) were identified among the groups during first trial of CS (conditioned stimulus) presentation (P > 0.05). Acute treatment with 0.25 g⋅kg-1 EGb significantly resulted in retention of original memory, without prevent acquisition of extinction within-session. In addition, our results showed, for the first time, that 32 proteins were affected in the dHF following treatment with 0.25, 0.50, and 1.00 g⋅kg-1 doses of EGb, which upregulated seven, 19, and five proteins, respectively. Additionally, EGb downregulated two proteins at each dose. These proteins are correlated with remodeling of the cytoskeleton; the stability, size, and shape of dendritic spines; myelin sheath formation; and composition proteins of structures found in the membrane of the somatodendritic and axonal compartments. Our findings suggested that EGb modulates conditioned suppression LTM through differential protein expression profiles, which may be a target for cognitive enhancers and for the prevention or treatment of neurocognitive impairments.

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Neuroprotective effects of Ginkgo biloba dropping pills in Parkinson's disease.

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