Chemical characterization, neuroprotective effect, and in-silico evaluation of the petroleum ether extract of three palm tree species against glutamate-induced excitotoxicity in rats

The burden of neurological disorders is growing substantially with limited therapeutic options, urging the consideration and assessment of alternative strategies. In this regard, we aimed to elucidate the phytochemical profile of the petroleum ether extract (PEE) of three palm tree species: <i>Aiphanes eggersii</i> Burret, <i>Carpoxylon macrospermum</i> H. Wendl. & Drude, and <i>Jubaeopsis caffra</i> Becc. (Family Arecaceae), and to evaluate their neuroprotective effect in monosodium glutamate (MSG)-induced excitotoxicity model for the first time. We identified a total of 48, 18, and 45 compounds in <i>A. eggersii</i>, <i>C. macrospermum,</i> and <i>J. caffra</i>, constituting 79.41 %, 60.45 %, and 76.35 % of the total detected compounds, respectively. <i>A. eggersii</i> extract was rich in the methyl esters of fatty acids (65.08 %) especially methyl dodecanoate (17.72 %). <i>C. macrospermum</i> was exclusively prolific by the triterpene 3<i>β</i>-methoxy-d:c-friedo-b':a'-neogammacer-9(11)-ene (40.36 %), while <i>J. caffra</i> was noticeable by hydrocarbons (30.14 %) and lupeol derivatives (19.79 %). The biochemical and histopathological analysis showed that the tested extracts significantly reduced the oxidative stress, especially at the highest tested dose (1000 mg/kg). The extracts also reduced the activity of induced nitric oxide synthetase, Ca⁺² level, and NR2B subunit expression and attenuated apoptosis and DNA damage. The docking results show that most active natural compounds bind to SOD-1 and NR2B-NMDARs, verifying the credibility of the biological findings. To sum up, the PEE of the three investigated palm tree species possessed a unique blend of lipophilic bioactive constituents that exert promising neuroprotective potential against MSG-induced excitoneurotoxicity. However, further preclinical investigation and pharmaceutical formulation are needed.