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Ginkgo biloba  leaf extract has been shown to increase the incidence in liver tumors in mice in a 2-year bioassay conducted by the National Toxicology Program. In this study, the DNA damaging effects of  Ginkgo biloba  leaf extract and many of its constituents were evaluated in human hepatic HepG2 cells and the underlying mechanism was determined. A molecular docking study revealed that quercetin, a flavonoid constituent of  Ginkgo biloba , showed a higher potential to interact with topoisomerase II (Topo II) than did the other  Ginkgo biloba  constituents; this  in silico  prediction was confirmed by using a biochemical assay to study Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the induction of γ-H2A.X, quercetin, followed by keampferol and isorhamnetin, appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II knockdown cells, DNA damage triggered by  Ginkgo biloba  leaf extract or quercetin was dramatically decreased, indicating that DNA damage is directly associated with Topo II. DNA damage was also observed when cells were treated with commercially available  Ginkgo biloba  extract product. Our findings suggest that  Ginkgo biloba  leaf extract- and quercetin - induced  in vitro  genotoxicity may be the result of Topo II inhibition.

Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II activity in human hepatic cells