Wang Xue, Shi Ya-Jin, Niu Ting-Yuan, Chen Ting-Ting, Li Han-Bing, Wu Su-Hui, Li Gen-Lin
Pharmacy College, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Medical College, Henan University of Chinese Medicine, Zheng-Zhou 450046, China.
Neurosci Lett. 2023 Sep 25;814:137439. doi: 10.1016/j.neulet.2023.137439. Epub 2023 Aug 12.
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-1β, and IL-18 levels, and increase IL-10 levels in the brain cortex. PPD also significantly alleviated the neurotoxicity by decreasing the Aβ and p-Tau in hippocampal DG, CA1, and CA3 areas. In addition, the levels of NLRP3, ASC, and IL-1β 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 Aβ deposition and Tau phosphorylation in 2-VO-induced VD rats.
20(S)-原人参二醇（PPD）是人参中的一种人参皂苷，据报道其可改善痴呆患者的认知功能。本研究旨在探讨PPD对双侧颈总动脉结扎（2-VO）诱导的血管性痴呆（VD）大鼠中NLRP3炎性小体介导的小胶质细胞焦亡的神经保护作用。将雄性Sprague-Dawley大鼠（无特定病原体级，150 - 180 g，每组n = 10）随机分为PPD组（20、10、5 mg/kg，皮下注射，每天1次，共3周）、模型组和假手术组。结果发现，PPD通过缩短逃避潜伏期和增加自发交替次数以及增加穿越平台次数，显著逆转了2-VO诱导的认知障碍，显示出记忆改善作用。PPD改善了VD大鼠脑组织的病理形态。PPD显著减小了脑梗死面积，并降低了皮质和海马齿状回、CA1和CA3区小胶质细胞的活化。此外，PPD可减轻NLRP3炎性小体介导的小胶质细胞焦亡，抑制NLRP3的阳性表达，降低大脑皮质中白细胞介素-1β和白细胞介素-18水平，并增加白细胞介素-10水平。PPD还通过降低海马齿状回、CA1和CA3区的β-淀粉样蛋白（Aβ）和磷酸化tau蛋白（p-Tau）水平，显著减轻了神经毒性。此外，PPD显著降低了皮质中NLRP3、凋亡相关斑点样蛋白（ASC）和白细胞介素-1β水平，以及海马中淀粉样前体蛋白（APP）、β-分泌酶1（BACE1）和p-Tau水平。这些结果表明，PPD可抑制小胶质细胞活化，减轻NLRP3炎性小体介导的神经炎症，并抑制2-VO诱导的VD大鼠中Aβ沉积和Tau磷酸化的神经毒性。
