Ginkgo biloba extract-induced mild oxidation might adapt cells against nitric oxide cytotoxicity

Oxidative stress can induce serious damage in cellular components, such as lipids, proteins and DNA, which compromises cell viability and can contribute to health problems. This oxidative state can be induced by excessive levels of signalling molecules such as nitric oxide, which can be converted into other molecules that can affect DNA integrity. Antioxidant plant extracts such as G. biloba L. can protect cells from oxidative stress, and thus promote human health. In this work, we evaluated the protective effect of a G. biloba leaf extract (GBE) against oxidative stress generated by sodium nitroprusside (SNP), an in vitro generator of nitric oxide, in Schizosaccharomyces pombe. The chemical analysis of GBE by electrospray ionization-mass spectrometry showed that the extract is mostly composed of flavonoids recognized by their strong antioxidant properties. Wild-type cells incubated with SNP and GBE showed higher survival than cells only incubated with SNP, indicating a protective effect. Mutant strains affected in base excision repair (mag1, apn2, nth1) and homologous recombination repair (rhp55) pathways were also protected from SNP, suggesting that GBE protection occurs by a DNA-repair independent mechanism. Cell cycle progression analysis revealed that GBE slightly reduces the delay caused by exposure to SNP. Cells incubated with SNP or GBE, or both, induced the relocalization of Pap1 into the nucleus. Pap1 is a transcription factor that is recruited to the nucleus upon oxidative stress, contributing to the expression of genes involved in oxidative stress response. Therefore, these results suggest that GBE may induce mild stress in cells, which can activate the oxidative stress response and consequently provide protection against SNP.This work is supported by: FCT - Portuguese Foundation for Science and Technology (PD/BD/135329/2017), under the Doctoral Programme “Agricultural Production Chains – from fork to farm” (PD/00122/2012); and by European Investment Funds by FEDER/COMPETE/POCI– Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013