Naringin has been shown to have significant

Naringin has been shown to have significant anti-inflammation, anti-oxidative stress, glucolipid metabolic regulation, and myocardial protection effects (Gopinath et al., 2011, Gopinath and Sudhandiran, 2012), suggesting that it may mitigate ADC by inhibiting P2X7 receptors. In the present study, naringin treatment markedly decreased the escape latency and target platform errors in gp120-treated rats, suggesting that naringin improved the gp120-induced learning and memory deficits of rats. Extracellular ATP is a natural ligand of the P2X family which opens the channel after combining with P2X receptors, resulting in inflow of Na+ and Ca2+ and outflow of K+ (Burnstock et al., 2011, Coddou et al., 2011). When the hcv protease inhibitor is infected or injured, the ATP released by the vesicle of damaged neurons triggers surrounding astrocytes to release more ATP (Monif et al., 2010, Ortega et al., 2012, Rodrigues et al., 2015). The ATP then activates the P2X7 receptors on neighboring microglia, inducing the microglial release of ATP through autocrine, which enlarges the ATP signal through the cascade process to maintain the chemotaxis state of microglia and results in altered ion permeability and, eventually, cell lysis and death (Burnstock et al., 2011, Skaper et al., 2010). In the present study, BzATP-induced current was enhanced considerably after gp120 hatching for 1h compared to the Ctrl, while the BzATP-induced current (which was enhanced by gp120) was inhibited after naringin hatching for 1h compared to the gp120 group. These results suggest that gp120 can enhance the current induced by P2X7 receptor’s specific agonist BzATP, while naringin may inhibit gp120-enhanced BzATP-induced current. We also found that HIV envelope glycoprotein gp120 induced the over-expression of P2X7 protein and mRNA in the hippocampus, but that naringin treatment inhibited the gp120-induced up-regulation of hippocampal P2X7 protein and mRNA expression in the rats. This suggests that naringin protected against gp120-induced learning and memory deficits by suppressing the expression of hippocampal P2X7 in the rats, which was further made clear by the fact that naringin had no effect on P2X7 protein/mRNA expression in the hippocampus of naïve rats. P65 protein expression also decreased in the naringin treatment group, suggesting that naringin may inhibit P65 protein expression to reduce the levels of NF-κB, thus generating a catabatic effect on gp120-induced learning and memory deficits. In summary, P2X7 may be involved in gp120-induced learning and memory deficits in rats, and naringin treatment may improve the learning and memory dysfunction caused by LV infusion of gp120, the mechanism of which may be related to blocking the up-regulated expression of P2X7 or inhibiting the expression of P65 protein to reduce NF-κB levels. The results discussed above may help researchers and developers to design ADC treatments in the future; this study not only potentially broadens the medicinal scope of naringin, but also represents a novel approach to the prevention and treatment of ADC.
Conflict of interest
Acknowledgements This work was supported by a grant (No. 81260187) from the National Natural Science Foundation of China, a grant (No. GJJ14146) from the Youth Science Foundation of the Educational Department of Jiangxi Province, a grant (No. 20153BCB23033) from the Cultivating Foundation of Young Scientists (Star of Jinggang) of Jiangxi Province, and grants (Nos. YC2014-S098 and YC2015-S040) from the Innovation Foundation of the Graduate School of Jiangxi Province. We would also like to thank Shangdong Liang Ph.D, Nanchang University, for participating in this study.
Introduction Gp120 is a glycoprotein present in the envelope of HIV virus and is responsible for viral entry into cells after interaction with CD4 and CXCR4 or CXCR5 receptors [1]. The pathogenic potential of gp120 in the Central Nervous System (CNS) has been shown in several studies that evaluate brain damage following expression of gp120 [2], [3].