Abstract
Ginkgo biloba extract 761 (EGb761), a standardized extract from the Ginkgo biloba leaf, is purported to inhibit NMDA receptor-mediated neuronal excitotoxicity and protect neurons form ischemic injury. However, the specific signal pathway involved in the effects of EGb761 on synaptic plasticity is still in dispute. In this article, effects of EGb761 and its monomer component ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC) and quercetin on rat hippocampal synaptic plasticity were studied. The evoked Excitatory postsynaptic currents (EPSCs) and miniature EPSCs were recorded on hippocampal slices from SD rats (14–21 days of age) by whole-cell patch-clamp recording and long-term potentiation (LTP) was induced by theta-burst stimulation. Acutely applied EGb761 inhibited the LTP, but bilaterally affect the evoked EPSCs. The evoked EPSCs were increased by incubation of lower concentration of EGb761, then the evoked EPSCs were decreased by incubation of higher concentration of EGb761. EGb761 monomer component GA, GB and GC could also inhibit the TBS-induced LTP and EPSC amplitude but not paired-pulse ratio (PPR). But quercetin, another monomer component of EGb761, led to increase in EPSC amplitude and decrease in PPR. Simultaneously, EGb761 and its monomer component ginkgolides inhibited the post-ischemic LTP (i-LTP) by inhibiting the EPSCs and the AMPA receptor subunit GluA1 expression on postsynaptic membrane. The results indicated that high concentration of EGb761 might inhibit LTP and i-LTP through inhibition effects of GA, GB and GC on AMPA receptors.
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Some or all data, code, or models generated or used during the study are available from the corresponding author by request.
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This article was sponsored by Grants of Natural Science Foundation of Jiangsu Province, China (BK20181471), National Natural Science Foundation of China (31801957), Grants of Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy (Xuzhou Medical University) (KF-XY201504). We thank Dr. Hu B. (Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, P.R. China) for excellent technical assistance.
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Y.L., S.-p.D., and Y.-f.L. designed research; Y.L., S.-p.D., Y.-f.L. Z.-c.Z. and Y.-t.C. performed research; Y.L. and Y.-k.L. analyzed data; Y.L., S.-p.D., Y.-f.L., and Y.-k.L. wrote the paper.
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Liu, Y., Ding, S., Luan, Y. et al. Ginkgo biloba extracts inhibit post-ischemic LTP through attenuating EPSCs in rat hippocampus. Metab Brain Dis 36, 2299–2311 (2021). https://doi.org/10.1007/s11011-021-00830-4
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DOI: https://doi.org/10.1007/s11011-021-00830-4