Geniposidic acid (GPA) is an extract from Eucommia ulmoides Oliv. Bark (Eucommiaceae). Accumulating evidences have reported GPA has anti-aging, anti-oxidative stress, anti-inflammatory and neurotrophic effects on neurons. However, whether GPA could alleviate memory deficits in Alzheimer's disease animal models is not clear. We aimed to investigate the effect of GPA treatment on cognitive performance, Aβ deposition and glial cells activation in the transgenic mouse model of AD. 6-7 months APP/PS1 mice were given GPA for 90 days; behavioral experiments were executed to estimate the memory and spatial learning abilities of mice, and the mechanism of neuroprotective effect of GPA was investigated with a focus on amyloid-β deposition, astrocytes and microglia activation and neuroinflammation. GPA treatment significantly improved the spatial learning and memory abilities and also decreased cerebral amyloid-β deposition in APP/PS1 mice. Via HE staining, we found that GPA could ameliorate histopathological changes in cerebrum. We also found that GPA treatment inhibited the activation of astrocytes and microglia, down-regulated the expression of pro-inflammatory cytokines and iNOS, and up-regulated the expression of anti-inflammatory cytokines and Arg-1. In addition, GPA down-regulated the gene expression of HMGB-1 receptors (TLR2, TLR4 and RAGE) then mediated MyD88, TRAF6 and phospho-ERK1/2, subsequently modulated the expression of key AP-1 and NF-κB family members (c-Fos, c-Jun and p65). The reversal of the pro-inflammatory state suggested GPA can serves as a multi-target candidate by alleviating Aβ deposition and neuroinflammation for the auxiliary therapy of Alzheimer's disease.

译文

:Geniposidicic acid(GPA)是杜仲杜仲的提取物。树皮(杜仲科)。越来越多的证据表明,GPA对神经元具有抗衰老,抗氧化应激,抗炎和神经营养作用。但是,GPA是否可以减轻阿尔茨海默氏病动物模型中的记忆缺陷尚不清楚。我们旨在研究GPA处理对AD转基因小鼠模型中认知能力,Aβ沉积和神经胶质细胞活化的影响。 6-7个月对APP / PS1小鼠给予GPA 90天;进行行为实验以估计小鼠的记忆和空间学习能力,并研究了GPA的神经保护作用机理,重点是淀粉样β沉积,星形胶质细胞和小胶质细胞活化以及神经炎症。 GPA处理显着改善了空间学习和记忆能力,还减少了APP / PS1小鼠的脑淀粉样β沉积。通过HE染色,我们发现GPA可以改善大脑的组织病理学变化。我们还发现,GPA治疗可抑制星形胶质细胞和小胶质细胞的活化,下调促炎性细胞因子和iNOS的表达,并上调抗炎性细胞因子和Arg-1的表达。此外,GPA下调HMGB-1受体(TLR2,TLR4和RAGE)的基因表达,然后介导MyD88,TRAF6和磷酸化ERK1 / 2,随后调节关键AP-1和NF-κB家族成员的表达( c-Fos,c-Jun和p65)。促炎状态的逆转提示,GPA可以通过减轻Aβ沉积和神经炎症来作为阿尔茨海默氏病的辅助疗法,从而成为多靶点候选药物。

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