Flavonoids from the fruits of Nepalese sumac (Rhus parviflora) attenuate glutamate-induced neurotoxicity in HT22 cells

Nepalese sumac (Rhus parviflora) is a wild edible fruit used for the treatment of various ailments including neurological complications and stomach disorders in the traditional medicinal system of south Asia (Ayurveda). Four flavonoids were isolated from ethyl acetate (EtOAc) fraction of Nepalese sumac fruits and their chemical structures were determined on the basis of NMR, fast atom bombardment mass spectrometry (FAB/MS), and IR. The efficiency of isolated compounds in attenuating glutamateinduced cell death in an immortalized mouse hippocampal cell line (HT-22) and inhibition of cycline dependent kinase 5 (Cdk5) were investigated. Among the compounds, flavanols, fustin (1) and taxifolin (2), an aurone, aureusidin (3), and a biflavonoid, agathisflavone (4) were found to have protective effect against glutamate induced oxidative injury in HT22 cells. Aureusidin (3), a Cdk5/p25 inhibitor (IC50 3.5 mu M), was the most potent neuroprotector with an EC50 value of 11.90 mu M.