Ginkgo biloba extract 50 alleviates memory and synaptic plasticity deficits by inhibiting neuroinflammation via the blockage of ATP-P2X7R axis in presenilin 1/2 conditional double knockout mice.
GBE50 shows potential in reducing neuroinflammation and improving cognitive function in a mouse model, but its relevance to human neurodegenerative diseases remains to be established.
Where it sits
this study against the rest of the dsip corpusSummary and findings
The study evaluated the effects of Ginkgo biloba extract 50 (GBE50) on neuroinflammation and cognitive dysfunction in presenilin 1/2 conditional double knockout mice. GBE50 treatment reduced inflammation markers and improved synaptic plasticity. The findings suggest modulation of the ATP-P2X7R-NLRP3 axis as a potential mechanism.
Abstract
<h4>Ethnopharmacological relevance</h4>Ginkgo biloba L. has been widely utilized in traditional Chinese medicine for its potential to enhance memory-related functions. In traditional medical practices, it is also commonly prescribed for conditions associated with cognitive decline and age-related disorders. These ethnopharmacological uses are closely linked to neurodegenerative disorders, in which neuroinflammation plays a central role. Ginkgo biloba has shown anti-inflammatory and neuroprotective properties, yet its underlying mechanisms in modulating neuroinflammation are still not fully understood.<h4>Aim of the study</h4>Neuroinflammation is critically involved in cognitive impairment and neurodegenerative diseases, while therapeutic options remain limited. Ginkgo biloba extract 50 (GBE50) is a standardized formulation with potential neuroprotective properties. This study aimed to assess its effects on neuroinflammation-associated cognitive dysfunction and to clarify the mechanisms involved.<h4>Methods</h4>Presenilin 1/2 conditional double knockout mice served as a cognitive impairment model, with behavioral tests used to evaluate cognitive function. The constituents of GBE50 were identified by UPLC-Q-TOF-MS, and ATP content was quantified using biochemical assays. The expression of P2X7 receptor, NLRP3 inflammasome-related proteins, inflammatory cytokines, and synaptic markers was determined at both mRNA and protein levels using qRT-PCR and Western blotting. Microglial activation and P2X7R distribution were assessed via immunofluorescence, and hippocampal synaptic plasticity was examined using electrophysiological recordings.<h4>Results</h4>Using UPLC-Q-TOF-MS, 51 compounds were characterized in GBE50, mainly flavonoids and terpene lactones, which are likely responsible for its biological activities. Treatment with GBE50 markedly alleviated cognitive impairment in PS cDKO mice. It downregulated P2X7R and key components of the NLRP3 inflammasome (NLRP3, NEK7, Caspase-1, and ASC), while also reducing the transcription of pro-inflammatory cytokines including Il-1β, Il-18, and Tnf-α. In parallel, GBE50 restored synaptic protein levels and improved long-term potentiation deficits.<h4>Conclusion</h4>Collectively, our findings suggest that modulation of the ATP-P2X7R-NLRP3 axis contributes to the neuroprotective effects of GBE50 in AD, highlighting this pathway as a promising therapeutic target for preventing AD-related neurodegeneration.
Background
This study addresses the role of neuroinflammation in cognitive impairment and neurodegenerative diseases, focusing on the potential therapeutic effects of Ginkgo biloba extract 50 (GBE50). Ginkgo biloba has been traditionally used for cognitive enhancement and has shown anti-inflammatory properties, but the mechanisms are not fully understood. Understanding these mechanisms could inform potential therapeutic strategies for neurodegenerative disorders.
Methods
The study used presenilin 1/2 conditional double knockout mice as a model for cognitive impairment. Behavioral tests assessed cognitive function, and UPLC-Q-TOF-MS identified GBE50 constituents. ATP content was measured biochemically, while qRT-PCR and Western blotting determined the expression of P2X7 receptor, inflammasome-related proteins, cytokines, and synaptic markers. Immunofluorescence assessed microglial activation and P2X7R distribution, and electrophysiological recordings examined hippocampal synaptic plasticity.
Results
GBE50 treatment in PS cDKO mice resulted in significant alleviation of cognitive impairment. There was a marked downregulation of P2X7R and NLRP3 inflammasome components, including NLRP3, NEK7, Caspase-1, and ASC. The transcription of pro-inflammatory cytokines such as Il-1β, Il-18, and Tnf-α was reduced. Additionally, GBE50 restored synaptic protein levels and improved deficits in long-term potentiation.
Interpretation
The study suggests that GBE50 may exert neuroprotective effects by modulating the ATP-P2X7R-NLRP3 axis, which could be a promising therapeutic target for Alzheimer's disease. However, the clinical significance of these findings is limited by the preclinical model used. Further research is needed to determine if these effects translate to human populations.
Key findings
- 51 compounds characterized in GBE50, mainly flavonoids and terpene lactones.
- GBE50 treatment markedly alleviated cognitive impairment in PS cDKO mice.
- Downregulation of P2X7R and NLRP3 inflammasome components observed.
- Reduced transcription of pro-inflammatory cytokines Il-1β, Il-18, and Tnf-α.
- Restored synaptic protein levels and improved long-term potentiation deficits.
Limitations
- mouse model, not human
- preclinical evidence only
- mechanistic focus, not clinical outcomes
- potential species-specific effects