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人参皂苷 Rg5 通过减轻神经炎症反应改善 STZ 诱导的记忆损伤大鼠的认知功能障碍和β-淀粉样蛋白沉积。

Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses.

机构信息

College of Agriculture, Anhui Agricultural University, Anhui, Hefei, 230036, PR China.

Key Laboratory of New Drug Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, 210028, PR China; Department of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, 210023, P. R. China.

出版信息

Int Immunopharmacol. 2014 Apr;19(2):317-26. doi: 10.1016/j.intimp.2014.01.018. Epub 2014 Feb 4.

Abstract

Neuroinflammatory responses play a crucial role in the pathogenesis of Alzheimer's disease (AD). Ginsenoside Rg5 (Rg5), an abundant natural compound in Panax ginseng, has been found to be beneficial in treating AD. In the present study, we demonstrated that Rg5 improved cognitive dysfunction and attenuated neuroinflammatory responses in streptozotocin (STZ)-induced memory impaired rats. Cognitive deficits were ameliorated with Rg5 (5, 10 and 20mg/kg) treatment in a dose-dependent manner together with decreased levels of inflammatory cytokines TNF-α and IL-1β (P<0.05) in brains of STZ rats. Acetylcholinesterase (AChE) activity was also significantly reduced by Rg5 whereas choline acetyltransferase (ChAT) activity was remarkably increased in the cortex and hippocampus of STZ-induced AD rats (P<0.05). In addition, Congo red and immunohistochemistry staining results showed that Rg5 alleviated Aβ deposition but enhanced the expressions of insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) in the hippocampus and cerebral cortex (P<0.05). Western blot analysis also demonstrated that Rg5 increased remarkably BDNF and IGF-1 expressions whereas decreased significantly Aβ deposits (P<0.05). Furthermore, it was observed that the expressions of COX-2 and iNOS were significantly up-regulated in STZ-induced AD rats and down-regulated strongly (P<0.05) by Rg5 compared with control rats. These data demonstrated that STZ-induced learning and memory impairments in rats could be improved by Rg5, which was associated with attenuating neuroinflammatory responses. Our findings suggested that Rg5 could be a beneficial agent for the treatment of AD.

摘要

神经炎症反应在阿尔茨海默病(AD)的发病机制中起着关键作用。人参皂苷 Rg5(Rg5)是人参中丰富的天然化合物,已被发现对 AD 的治疗有益。在本研究中,我们证明 Rg5 改善了链脲佐菌素(STZ)诱导的记忆受损大鼠的认知功能障碍,并减轻了神经炎症反应。Rg5(5、10 和 20mg/kg)以剂量依赖性方式改善了认知障碍,同时降低了 STZ 大鼠大脑中炎症细胞因子 TNF-α和 IL-1β的水平(P<0.05)。Rg5 还显著降低了乙酰胆碱酯酶(AChE)的活性,而胆碱乙酰转移酶(ChAT)的活性在 STZ 诱导的 AD 大鼠的皮质和海马中显著增加(P<0.05)。此外,刚果红和免疫组织化学染色结果表明,Rg5 减轻了 Aβ的沉积,但增强了海马和大脑皮质中胰岛素样生长因子 1(IGF-1)和脑源性神经营养因子(BDNF)的表达(P<0.05)。Western blot 分析还表明,Rg5 显著增加了 BDNF 和 IGF-1 的表达,而显著减少了 Aβ的沉积(P<0.05)。此外,观察到 COX-2 和 iNOS 的表达在 STZ 诱导的 AD 大鼠中显著上调,并被 Rg5 强烈下调(与对照组相比,P<0.05)。这些数据表明,Rg5 可改善 STZ 诱导的大鼠学习和记忆障碍,这与减轻神经炎症反应有关。我们的研究结果表明,Rg5 可能是治疗 AD 的一种有益药物。

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