Supplementation of lycopene attenuates lipopolysaccharide-induced amyloidogenesis and cognitive impairments via mediating neuroinflammation and oxidative stress

Abstract

Neuroinflammation is documented to be the major culprit of Alzheimer's disease. Lycopene (LYC), a fat soluble carotenoid, exhibits neuroprotective function in several neurodegenerative disorders. However, the effects of LYC to countering systemic inflammation-induced amyloidogenesis and memory deficiency remain to be elucidated. In current study, 3-month-old male C57BL/6J mice were treated with 0.03% LYC (w/w, mixed into normal chow) for 5 weeks. The mice were then treated by intraperitoneal injection of LPS (0.25mg/kg) for 9 days. It was found that LYC inhibited LPS-induced memory loss by behavior tests including Y-maze test and Morris water test. Meanwhile, LYC prevented LPS-induced accumulation of Aβ, levels of amyloid precursor protein (APP), and suppressed neuronal β-secretase BACE1 and elevated the expressions of α-secretase ADAM10. Furthermore, LYC down-regulated the expression of IBA-1 (a marker of microglia activation), reduced the levels of inflammatory mediators and inhibited oxidative stress in LPS-treated mice. Moreover, LYC suppressed the phosphorylation of MAPKs, NFκB, and activated Nrf2 signaling pathways in LPS-treated BV2 microglial cells. Therefore, our study indicated that LYC could ameliorate LPS-induced neuroinflammation, oxidative stress, amyloidogenesis and cognitive impairments possibly through mediating MAPKs, NFκB and Nrf2 signaling pathways, indicating that LYC might be a nutritional preventive strategy in neuroinflammation-related diseases such as AD.