Lycium barbarum polysaccharide protects against neurotoxicity via the Nrf2-HO-1 pathway

The incidence of neurodegenerative diseases including Alzheimer's and Parkinson's disease has markedly increased over the past few decades. Oxidative stress is considered to be a common pathophysiological condition resulting in neurotoxicity. Lycium barbarum polysaccharide (LBP) is the major active component of Lycium barbarum L., which exhibit potent antioxidant activity. The current study investigated the neuroprotective effects of LBP in H(2)O(2)-treated PC12 cells in vitro and in CoCl(2)-treated rats in vivo. It was determined that LBP concentration-dependently reversed the H(2)O(2)-induced increase in reactive oxygen species (ROS) levels, decrease in cell viability, increase in TUNEL-stained cells, increase in caspase-3 and −9 activity and decrease in mitochondrial membrane potential, indicating the amelioration of mitochondrial apoptosis. Furthermore, LBP inhibited the H(2)O(2)-induced decrease in nuclear factor erythroid 2-related factor 2 (Nrf)2 and heme oxygenase (HO)-1 expression and binding of Nrf2 to the promoters of HO-1. Silencing of Nrf2 and inhibition of HO-1 by zinc protoporphyrin IX (ZnPP) reversed the protective effects of LBP against H(2)O(2)-resulted neurotoxicity in PC12 cells. In CoCl(2)-treated rats, it was demonstrated that LBP decreased brain tissue apoptosis, reduced the time spent by rats finding the platform site, decreased escape latencies and reduced the distance traveled to find the platform. In addition, LBP inhibited the CoCl(2)-induced decrease of Nrf2 and HO-1 expression. Administration of ZnPP also suppressed the protective effects of LBP against CoCl(2)-resulted neurotoxicity in rats. Thus, the current study indicated that LBP exhibits protective effects against neurotoxicity by upregulating Nrf2/HO-1 signaling. These data may increase understanding regarding the neuroprotective activities of LBP.