Protective effect against oxidative neuron cell injury of Amaryllidaceae alkaloids

Oxidative stress is an excessive production of reactive species and insufficient activity of antioxidant defense mechanisms have been implicated as one of the important player in the pathogenesis of Alzheimer disease (AD), where the disturbance in systems employing the excitatory neurotransmitter L-glutamate may underlie part of its pathogenic mechanisms [1]. Amaryllidaceae alkaloids are capable of penetrating the blood-brain barrier, decrease oxidative damage and chronic neurodegeneration [2]. However, its antioxidant mode of action is not clear. Species of the family Amaryllidaceae (Clivia miniata, Eucharis bonplandii, Eucharis caucana) were collected in Colombia and their respective alkaloid fractions were obtained. The antioxidant activity was evaluated by Oxigen Radical Absorbance Capacity and Ferric Reducing Antioxidant Power assays, where the alkaloidal fraction of E. bonplandii presented the highest antioxidant capacity by both methods with values of 4538.96 ± 140.00 and 574.66 ± 7.77µmol Trolox/g alkaloidal fraction, respectively. The cytotoxicity and neuroprotective activity of the fractions was evaluated in a model of glutamate excitotoxicity in primary cultures of neurons at 0.75, 1.5, 3.0 and 6.0 µg/mL concentrations. E. bonplandii protected the neurons after the toxic stimulus at 6.0 µg/mL. This neuroprotection was related by the formation of Thiobarbituric Acid Reactive Substances, where E. bonplandii reduced significantly the oxidation of the cell membrane 45.45% with respect to the oxidation generated by L-glutamate. This evidence of antioxidant activity and lipid peroxidation may be involved in the neuroprotective activity, where the stabilization of free radicals should be associated with the ability of alkaloids to donating the hydrogen atom of the enol group.

[1] Dong X, Wang Y, Qin Z: Acta Pharmacol Sin 2009;30:379 – 387.

[2] Traykova M, Traykov T, Hadjimitova V, Krikorian K, Bojadgieva N: Z Naturforsch C 2003;58:361 – 5.