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Neurosci Lett ; 814: 137439, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37579868

RESUMO

20(S)-protopanaxadiol (PPD), one of the ginsenosides from Panax ginseng, has been reported to improve performance with dementia. This study aimed to investigate the neuroprotective effect of PPD attenuating NLRP3 inflammasome-mediated microglial pyroptosis in vascular dementia (VD) rats induced by bilateral common carotid artery ligation (2-VO). Male Sprague-Dawley rats (SPF, 150-180 g, n = 10/group) were randomly divided into PPD (20, 10, 5 mg/kg, subcutaneous injection once per day for 3 weeks), model, and vehicle-sham group. It was found that PPD significantly reversed 2-VO-induced cognitive impairment by decreasing escape latency and spontaneous alternation and increasing the number of crossing platforms, showing memory-improving effects. PPD improved the pathological morphology of brain tissue in VD rats. PPD significantly reduced the cerebral infarction area and the activation of microglia in the cortex and hippocampal DG, CA1, and CA3 area. Moreover, PPD could attenuate NLRP3 inflammasome-mediated microglial pyroptosis, inhibit the positive expression of NLRP3, decrease IL-1ß, and IL-18 levels, and increase IL-10 levels in the brain cortex. PPD also significantly alleviated the neurotoxicity by decreasing the Aß and p-Tau in hippocampal DG, CA1, and CA3 areas. In addition, the levels of NLRP3, ASC, and IL-1ß in the cortex, APP, BACE1, and p-Tau in the hippocampus were significantly reduced by PPD. These results suggested that PPD hinders microglial activation to alleviate neuroinflammation of NLRP3 inflammasome and inhibits neurotoxicity of Aß deposition and Tau phosphorylation in 2-VO-induced VD rats.


Assuntos
Demência Vascular , Fármacos Neuroprotetores , Ratos , Masculino , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/metabolismo , Demência Vascular/metabolismo , Microglia/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ratos Sprague-Dawley , Piroptose , Ácido Aspártico Endopeptidases/metabolismo
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