Effects and mechanisms of caesalpinia mimosoides leaf extract on oxidative stress resistance and anti-aging activity in caenorhabditis elegans and neurite outgrowth activity in neuro2a cells

Abstract

World’s population of older people is rising, dietary supplements promoting healthy lifespan are needed. Moreover, Alzheimer’s disease (AD), an age-related degenerative disease, becomes a public health problem in aging society. Recent reports using cell culture models of AD suggest that amyloid precursor protein (APP), a protein causally related to AD, plays an important role as an inhibitor of neurite outgrowth. Medicinal herbs with neurite outgrowth stimulatory effect may help to prevent and cure AD. Moreover, studies suggest that dietary supplements from plant sources act in preventive nutrition, since they provide antioxidant action against oxidative stress, promote healthspan and prolong lifespan. Therefore, this study aimed to investigate the neurite outgrowth promoting activity along with its possible underlying mechanisms of Thai plants using both normal and APP-overexpressing neuronal cell lines Neuro2a and Neuro2a/APPSwe, respectively .as well as antioxidant and anti-aging of the plants using in vivo model, Caenorhabditis elegans. The results found that the methanol extract of twigs and leaves of Caesalpinia mimosoides (CM) could stimulate neurite outgrowth of both normal and APP-overexpressing cells. After treatment with the extract, the mRNA expression of growth associated protein-43 (GAP-43) and teneurin-4 (Ten-4) genes, the markers of neurite outgrowth activation, were increased in both Neuro2a and Neuro2a/APPSwe cells, while the mRNA expression of neurite outgrowth negative regulators, Nogo receptor (NgR) and its co-receptor Lingo-1 were found reduced. The overall results suggest that CM extract promotes neurite outgrowth against overexpression of APP in neuronal cells via up-regulated expression of GAP-43 and Ten-4 and down-regulated expression of Lingo-1 and NgR. A leaf extract of C.M improved resistance to oxidative stress and reduced intracellular ROS accumulation in nematodes. The antioxidant effects were mediated through the DAF-16/FOXO pathway and SOD-3 expression, whereas the expression of SKN-1 and GST-4 were not altered. The extract also decreased aging pigments, while the body length and brood size of the worms were not affected by the extract, indicating low toxicity and excluding dietary restriction. The results of this study establish neurite outgrowth stimulatory effects in APP-overexpressing neurons and the antioxidant activity of CM extract in vivo and suggest its potential as a dietary supplement and alternative medicine to treatment of AD, oxidative stress and aging, which should be investigated in intervention studies.