Neuroprotective flavonoids of the leaf of Antiaris africana Englea against cyanide toxicity

Different parts of Antiaris africana Englea (Moraceae) are used traditionally for the treatment of various diseases, including epilepsy and other nervous system disorders.The current study was designed to evaluate the neuroprotective activity of flavonoids isolated from A. africana against potassium cyanide (KCN)-induced oxidative damage in brain homogenate.Dried and ground leaves of A. africana were extracted with methanol and fractioned into n-hexane (HFA), dichloromethane (DFA), ethyl acetate (EFA) and methanol (MFA). Each fraction was assessed for neuroprotective potential by anticholinesterase activity test. The fraction with the best anticholinesterase activity was subjected to various chromatographic techniques through bioassay-guided fractionation to isolate the bioactive compounds. The protective ability of the extract, fractions and compounds against Potassium cyanide (KCN)-induced mitochondrial damage in rat brain homogenate was evaluated. Structures of the isolated compounds were determined using 1D and 2D NMR, mass spectrometry and by comparison with literature data.The ethyl acetate fraction showed the best anticholinesterase activity with an IC₅₀ of 23.23 ± 1.12 μg/ml. Quercetin and a biflavonoid glucoside identified as 3′-4′-bisquercetin-3β-D-diglucoside from this fraction displayed a remarkable antioxidant activity in the DPPH assay and showed significant (P < 0.05) increase in the activity of dehydrogenase inhibited by KCN in a concentration dependent manner. However, quercetin was more effective in reducing the MDA level and acetylcholinesterase activity that were elevated by KCN.Quercetin and the bisquercetin-diglucoside isolated from the leaves of A. Africana for the first time, are major contributors to the observed neuroprotective property of the plant which supports its folkloric usage in the management of seizures, epilepsy and other neurological disorders.