Effects and mechanisms of anacardium occidentale and glochidion zeylanicum leaf extracts on neuroprotective, neuritogenesis, oxidative stress resistance and anti-aging properties.

Abstract

Aging is the primary risk factor for most neurodegenerative diseases and can negatively affect the quality of life. Neurodegenerative diseases are linked to neuronal cell death and neurite outgrowth impairment that are often caused by oxidative stress. As people want to live longer and healthier, healthy nutrition has been increasingly received much attention in recent years. Several studies reported a positive correlation between antioxidants in foods and longevity. Natural products from food supplements and medicinal plants with antioxidant properties could be promising candidates for fighting against various aging-related diseases and promoting longevity. Leaf extracts from A. occidentale (AO) and G. zeylanicum (GZ) have been of great interest due to their pronounced antioxidant effects. However, the anti-oxidant and anti-aging effects of AO and GZ leaf extracts still have not been reported. The current study aims to document beneficial effects of leaf extracts from AO and GZ extracts with neuroprotective, neuritogenesis, oxidative stress resistance properties and lifespan extension in the cultured neuronal (HT22 and Neuro-2a) cells and the C. elegans model. In cultured neuronal cell models, the AO and GZ extracts have a protective effect against glutamate/H2O2-mediated oxidative stress-induced cell death via inhibition of ROS accumulation, up-regulation of endogenous antioxidant enzymes, and the increase of the SIRT1-Nrf2 signaling pathway. The AO and GZ extracts increase neurite outgrowth mediated Ten-4 transmembrane protein. In C.elegans models, the AO and GZ extracts mediated the survival rate of nematodes under oxidative stress by stimulation stress-response genes (SOD-3 and GST-4), attenuating intracellular reactive oxygen species (ROS) accumulation via DAF-16/FoxO and SKN-1/Nrf-2 signaling pathway. The AO and GZ extracts exhibited anti-aging activities and enhanced longevity by improving pharyngeal pumping function, attenuation of pigment accumulation (lipofuscin) and a lifespan extension in wild-type worm. Collectively, this study is the first report about the phytochemical composition of A. occidentale and G. zeylanicum along with neuroprotective, neuritogenesis, antioxidant and anti-aging effects in cultured neuronal cells (In vitro) and C. elegans models (In vivo). Our novel findings could initiate further applications of AO and GZ leaf extracts as natural products beneficial to humans for developing new treatment and protection aging-related diseases in the future.