Pananx notoginseng saponins attenuate CCL2-induced cognitive deficits in rats via anti-inflammation and anti-apoptosis effects that involve suppressing over-activation of NMDA receptors

Biomedicine & Pharmacotherapy

Yan Zhou¹  Kiran Sapkota²  Yuan-jun Liao³  Jin-bin Wei³  Yi-jun Zhou³  Jian-min Chen³  Jiang-yi Long³  Jun-jun Jiang⁴  Bing-yu Liang⁴ 

[1] Corresponding authors.;Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, United States;Department of Pharmacology, Guangxi Medical University, Nanning, Guangxi, 530021, China;Guangxi key laboratory of AIDS Prevention and Treatment, Guangxi Medical University, Nanning, Guangxi, 530021, China;

关键词: PNS;    HIV-associated neurocognitive disorder;    CCL2;    oxidative stress;    apoptosis;    inflammation;   

DOI  :  

来源: DOAJ

【 摘 要 】

HIV-associated neurocognitive disorders (HAND) are characterized by synaptic damage and neuronal loss in the brain, ultimately leading to progressive decline of cognitive abilities and memory. Chemokine CC motif ligand 2 (CCL2) is elevated in cerebrospinal fluid (CSF), and has been believed to contribute to HAND. Previous studies by our research team have shown that CCL2 enhances N-Methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) and causes nerve cell damage. However, there are few drugs currently available to treat nerve damage that is caused by CCL2. Panax notoginseng saponins (PNS) are isolated from Panax notoginseng and benefit the human body in various ways, including the neuroprotective effect. However, the protective effect of PNS on CCL2-induced neurotoxicity remains unknown. In this study, we found that PNS improved CCL2-induced learning and memory impairment, and inhibited CCL2-induced cell death. These effects may be due to inhibiting over-activation of NMDA receptors by alleviating the dysfunction of glutamate metabolism. Furthermore, PNS-modulated CCL2-inducd intracellular oxidative stress was found to attenuate cell inflammation. Additionally, PNS pretreatment evidently inhibited apoptotic pathways by reducing the Bax/BCL-2 ratio and caspase-3, 8, 9 expressions. In conclusion, this study demonstrates that PNS provides substantial neuroprotection against CCL2-induced neurotoxicity, and may be a novel therapeutic agent in CCL2-induced HAND or other neurodegenerative diseases.

【 授权许可】

Unknown