Standardized extract of Ginkgo biloba enhances memory persistence over time

Abstract

BackgroundPreviously, our group has shown that treatment with a standardized extract of Ginkgo biloba leaves (EGb) before acquisition/encoding of the conditioned suppression and object recognition task produced recent memory persistence by upregulating CREB-1 and BDNF in the hippocampal formation in a dose-dependent manner. Moreover, memory durability is influenced by processes that occur after encoding. Since the effects of EGb on consolidation processes and memory persistence are unknown, the characterization of these effects will help elucidate both the beneficial and harmful effects of “cognitive enhancers” treatments. MethodsWe investigated the effects of EGb treatment (250, 500 and 1000 mg Kg−1) on consolidation of conditioned lick suppression memory and its persistence, i.e., assessing fear memory retrieval and extinction, 2–4 days (recent long-term memory) or 40–42 days (remote long-term memory) after its acquisition. We also analyzed the compounds in the EGb by UHPLC-HRMS/MS and molecular networking (MN) for dereplication. ResultsWe show, for the first time, that EGb-induced persistence of conditioned suppression. Interestingly, while a higher dose promoted both recent and remote long-term memory persistence without preventing the acquisition of fear extinction memory, the lower dose induced the persistence of original fear remote memory and prevented extinction fear memory formation. The intermediate dose seems to be related to anti-anxiety effects. Furthermore, dereplication of EGb assisted by GNPS detected, besides ginkgolides A, B and D, distinct flavonoids, including quercetin, rutin and nicotiflorin. ConclusionThis study is the first to show that EGb treatment modulates recent and remote fear memory consolidation and its persistence. Additionally, our phytochemical analysis of the EGb corroborates the presence of flavonoids and terpenoids, which may account for the biological effects of EGb on the duration of memory and shed light on its potential as an adjunct to the treatment of memory decline or anxiety disorders.