Abstract
Ginkgo biloba L. leaf extracts and herbal infusions are used worldwide due to the health benefits that are attributed to its use, including anti-neoplastic, anti-aging, neuro-protection, antioxidant and others. The aim of this study was to evaluate the effect of an aqueous Ginkgo biloba extract on HepG2 cell viability, genotoxicity and DNA protection against paraquat-induced oxidative damage. Exposure to paraquat (PQ), over 24 h incubation at 1.0 and 1.5 µM, did not significantly reduce cell viability but induced concentration and time-dependent oxidative DNA damage. Ginkgo biloba leaf extract produced dose-dependent cytotoxicity (IC50 = 540.8 ± 40.5 µg/mL at 24 h exposure), and short incubations (1 h) produced basal and oxidative DNA damage (>750 and 1500 µg/mL, respectively). However, lower concentrations (e.g., 75 µg/mL) of Ginkgo biloba leaf extract were not cytotoxic and reduced basal DNA damage, indicating a protective effect at incubations up to 4 h. On the other hand, longer incubations (24 h) induced oxidative DNA damage. Co-incubation of HepG2 cells for 4 h, with G. biloba leaf extract (75 µg/mL) and PQ (1.0 or 1.5 µM) significantly reduced PQ-induced oxidative DNA damage. In conclusion, the consumption of Ginkgo biloba leaf extract for long periods at high doses/concentrations is potentially toxic; however, low doses protect the cells against basal oxidative damage and against environmentally derived toxicants that induce oxidative DNA damage.
Highlights
Plants and herbs have been used since ancient times and today many people still rely on medicinal plants for their primary health care, others use them as a natural source of bioactive molecules
Data on the antioxidant activity of Ginkgo biloba leaf extract are inconsistent; some authors highlight its ability as an antioxidant with the ability to scavenge hydrogen peroxide [13,14], as a protector against membrane lipid peroxidation [15], and its ability to increase reduced glutathione (GSH) levels [5]; others have suggested that the G. biloba extract is pro-oxidant [16,17] or even cytotoxic [3,18,19], which can probably be attributed to some compounds present in the whole leaf extract that may act per se or in combination in a synergistic way
For 24 h did not alter cell viability, as measured by the cell viability indicator Alamar Blue (Figure 1A). These results are in agreement with others obtained in other cell models, for example, in human neural progenitor cells, a slight reduction on cell viability (~95% cell viability) was observed after 24 h exposure to 10 μM PQ [25], but 90% cell viability was observed upon exposure of rat mesencephalic dopaminergic neuronal N27 cells [26] or HepG2 [27] to 100 μM PQ
Summary
Plants and herbs have been used since ancient times and today many people still rely on medicinal plants for their primary health care, others use them as a natural source of bioactive molecules. Data on the antioxidant activity of Ginkgo biloba leaf extract are inconsistent; some authors highlight its ability as an antioxidant with the ability to scavenge hydrogen peroxide [13,14], as a protector against membrane lipid peroxidation [15], and its ability to increase reduced glutathione (GSH) levels [5]; others have suggested that the G. biloba extract is pro-oxidant [16,17] or even cytotoxic [3,18,19], which can probably be attributed to some compounds present in the whole leaf extract that may act per se or in combination in a synergistic way. These differences may arise from the methodology used, i.e., indirect methods, such as the assessment of antioxidant enzymes, studying single compounds present in the extract, or directly measuring the antioxidant activity of the extract or its fractions
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