Identification of Kaempferol as a Monoamine Oxidase Inhibitor and Potential Neuroprotectant in Extracts of Ginkgo Biloba Leaves

The effects of Ginkgo biloba leaf extract on rat brain or livermonoamine oxidase (MAO)‐A and ‐B activity, biogenic amine concentration in nervous tissue, N‐methyl‐d‐aspartate (NMDA)‐ and N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine (DSP‐4)‐induced neurotoxicity and antioxidant activity was investigated to determine the effects of the extract on monoamine catabolism and neuroprotection. Ginkgo biloba leaf extract was shown to produce in‐vitro inhibition of rat brain MAO‐A and ‐B. The Ginkgo biloba extract was chromatographed on a reverse‐phase HPLC system and two of the components isolated were shown to be MAO inhibitors (MAOIs). These MAOIs were identified by high‐resolution mass spectrometry as kaempferol and isorhamnetin. Pure kaempferol and a number of related flavonoids were examined as MAOIs in‐vitro. Kaempferol, apigenin and chrysin proved to be potent MAOIs, but produced more pronounced inhibition of MAO‐A than MAO‐B. IC50 (50% inhibition concentration) values for the ability of these three flavones to inhibit MAO‐A were 7 times 10−7, 1 times 10−6 and 2 times 10−6 m, respectively. Ginkgo biloba leaf extract and kaempferol were found to have no effect ex‐vivo on rat or mouse brain MAO or on concentrations of dopamine, noradrenaline, 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid. Kaempferol was shown to protect against NMDA‐induced neuronal toxicity in‐vitro in rat cortical cultures, but did not prevent DSP‐4‐induced noradrenergic neurotoxicity in an in‐vivo model. Both Ginkgo biloba extract and kaempferol were demonstrated to be antioxidants in a lipid‐peroxidation assay. This data indicates that the MAO‐inhibiting activity of Ginkgo biloba extract is primarily due to the presence of kaempferol. Ginkgo biloba extract has properties indicative of potential neuroprotective ability.