Antioxidant activities of three phenolic alkaloids, i.e., oleracein A (OA), oleracein B (OB) and oleracein E (OE), isolated from Portulaca oleracea were determined, based on scavenging activity against 1,1-diphenyl- 2-picryl-hydrazyl (DPPH) radical and inhibitory effect on hydrogen peroxide-induced lipid peroxidation in rat brain homogenates. The DPPH radical scavenging activities of these phenolic alkaloids were lower than caffeic acid but higher than ascorbic acid and alpha-tocopherol, being in the following order: OB > OA > OE. OE was most potent in preventing formation of malondialdehyde (MDA) with an EC(50) value of 73.13 microM, close to that of caffeic acid (72.09 microM). It was demonstrated that phenolic alkaloids served as a new class of antioxidant agents in this plant.

Oleracein E (OE), a tetrahydroisoquinoline possessing potent antioxidant activity, was first isolated from a traditional Chinese medicine, Portulaca oleraea L., and is hypothesized to be a neuroprotectant. In the present study, we evaluated the effects of racemic OE on rotenone-induced toxicity in Parkinson's disease (PD) cell and animal models. Pretreatment with OE (10 μM, 2 h) decreased lactic acid dehydrogenase (LDH) release and the apoptosis rate in rotenone (5 μM, 24 h)-treated SH-SY5Y human neuroblastoma cells. Further mechanistic study indicated that OE reduced reactive oxygen species (ROS) levels, inhibited extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, reduced rotenone-induced up-regulation of the proapoptotic protein Bax, and prevented cytochrome C release and caspase-3 activation. In a rotenone-treated (intragastric 30 mg/(kg·d), 56 d) C57BL-6J mouse model, OE (intragastric 15 mg/(kg·d), 56 d) improved motor function, as indicated by an increased moving distance in the spontaneous activity test and sustained time on the rota-rod test. OE also elevated superoxide dismutase (SOD) activity, decreased malonaldehyde content, and reduced ERK1/2 phosphorylation in the midbrain and striatum of mice treated with rotenone. Furthermore, OE preserved tyrosine hydroxylase-positive neurons and maintained the density of dopaminergic (DAergic) fibers in the substantia nigra pars compacta (SNpc). Some of the effects of OE on PD models were similar to those of the positive control selegiline hydrochloride. Our results demonstrated that OE protects DAergic neurons against rotenone toxicity through reducing oxidative stress and down-regulating stress-related molecules. OE is worth exploring further for its neuroprotectant properties in the prevention and treatment of PD.

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