Effects of herbal plant extracts on oxidative stress and neuroinflammatory mechanisms in cultured neuronal cells : a model for alzheimer's disease prevention

Abstract

Traditional medicine employs a wide range of native herbs containing a variety of substances which are used to treat several disorders. Amaranthus plants or spinach are rich in antioxidant compounds which play a role in scavenging free radicals and are known to possess medicinal properties. Oxidative stress caused by aberrant production of reactive oxygen species (ROS) and neuroinflammation represents important mechanisms for neuronal dysfunction and cell loss of many neurodegenerative diseases such as Alzheimer's disease (AD). Advanced glycation endproducts (AGEs) can lead to the pathological changes of AD by interaction with their receptor (RAGE) elicits the formation of ROS that are believed to occur early in AD pathology. So far no work has been reported on neuroprotective effect of Amaranthus extract on AGEs-induced AD pathology. In the present study, petroleum ether, dichloromethane and methanol were used to extract leaves of Amaranthus lividus and Amaranthus tricolor; the extracts were analyzed for antioxidant activity which was found to be the highest in the methanol fraction of both kinds of the plants. Human neuroblastoma cell lines, SH-SY5Y, were induced to oxidative damage upon incubation with AGEs as shown by an increase in oxidative stress as well as a significantly upregulated oxidative gene, HMOX-1 resulting in reducing cell viability and increasing cell toxicity in a dose dependent manner. AGEs could induce RAGE and the consequent activation of NF-κB genes expression and were able to upregulate BACE1, PS1 expression that involved in amyloid beta production, pathologic hallmark of AD, and gene expression of pro-inflammatory cytokines, TNF-α, IL-1 and IL-6. Upon incubation with A. lividus and A. tricolor extracts, they were effective at reducing oxidative stress and were dose dependently capable to attenuate the neuron toxicity caused by AGEs treatment. Interestingly, the extracts significantly decreased the expression of the HMOX-1, RAGE and NF-κB genes. Moreover, the results showed BACE1, PS1 and proinflammatory cytokine genes expression were significantly downregulated when AGEs-induced cells were treated with the plant extracts. The present data suggest that A. lividus and A. tricolor extracts not only have neuroprotective effect against AGEs-induced oxidative damage but also have anti-inflammatory activity by reducing pro-inflammatory cytokine gene expression and attenuate Alzheimer-like pathophysiological changes by down-regulating the key enzyme for amyloid beta production. The neuroprotective effects of these plants may be associated with their inhibitory actions via the RAGE/NF-kB pathway. The present data support the utilization of these plants for beneficial effect on the cognitive performance from AD and may provide a new to the possibility of using the herbal extracts for potential therapy of AD.