Yang Yujie, Li Shanshan, Huang Hong, Lv Jingwei, Chen Shanguang, Pires Dias Alberto Carlos, Li Yujiao, Liu Xinmin, Wang Qiong
Affiliated TCM Hospital, School of Pharmacy, Sino-Portugal TCM International Cooperation Center, Southwest Medical University, Luzhou, China.
Research Center for Pharmacology & Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Pharmacol. 2020 Jun 10;11:834. doi: 10.3389/fphar.2020.00834. eCollection 2020.
This present study was designed to investigate the different effects of ginsenosides Rb1 and Rg1 on improving cognitive deficits in 4-month-old SAMP8 mice. Mice were divided into six groups, including the SAMP8 group, the SAMP8 + Donepezil (1.6 mg/kg) group, the SAMP8 + Rb1 (30 and 60 µmol/kg), and SAMP8 + Rg1 (30 and 60 µmol/kg) groups. SAMR1 mice of the same age were used as the control group. Ginsenosides and donepezil were administrated orally to animals for 8 weeks, then the learning and memory ability of mice were measured by using Morris water maze (MWM) test, object recognition test and passive avoidance experiments. The possible mechanisms were studied including the anti-glial inflammation of Rb1 and Rg1 using HE staining, immunohistochemistry and western blot experiments. Results revealed that Rb1 and Rg1 treatment significantly improved the discrimination index of SAMP8 mice in the object recognition test. Rb1 (60 µmol/kg) and Rg1 (30, 60 µmol/kg) could significantly shorten the escape latency in the acquisition test of the MWM test in SAMP8 mice. Furthermore, Rb1 and Rg1 treatments effectively reduced the number of errors in the passive avoidance task in SAMP8 mice. Western blot experiments revealed that Rb1 showed higher effect than Rg1 in decreasing protein expression levels of ASC, caspase-1 and Aβ in the hippocampus of SAMP8 mice, while Rg1 was more effective than Rb1 in decreasing the protein levels of iNOS. In addition, although Rb1 and Rg1 treatments showed significant protective effects in repairing neuronal cells loss and inhibiting the activation of astrocyte and microglia in hippocampus of SAMP8 mice, Rb1 was more effective than Rg1. These results suggest that Rb1 and Rg1 could improve the cognitive impairment in SAMP8 mice, and they have different mechanisms for the treatment of Alzheimer's disease.
本研究旨在探讨人参皂苷Rb1和Rg1对改善4月龄SAMP8小鼠认知缺陷的不同作用。将小鼠分为六组,包括SAMP8组、SAMP8 + 多奈哌齐(1.6 mg/kg)组、SAMP8 + Rb1(30和60 µmol/kg)组以及SAMP8 + Rg1(30和60 µmol/kg)组。将同年龄的SAMR1小鼠作为对照组。人参皂苷和多奈哌齐经口给予动物8周,然后通过莫里斯水迷宫(MWM)试验、物体识别试验和被动回避实验来测量小鼠的学习和记忆能力。利用苏木精-伊红染色、免疫组织化学和蛋白质印迹实验研究包括Rb1和Rg1的抗神经胶质炎症等可能机制。结果显示,Rb1和Rg1处理显著提高了SAMP8小鼠在物体识别试验中的辨别指数。Rb1(60 µmol/kg)和Rg1(30、60 µmol/kg)可显著缩短SAMP8小鼠在MWM试验获取试验中的逃避潜伏期。此外,Rb1和Rg1处理有效减少了SAMP8小鼠在被动回避任务中的错误次数。蛋白质印迹实验显示,Rb1在降低SAMP8小鼠海马中ASC、半胱天冬酶-1和Aβ的蛋白表达水平方面比Rg1表现出更高的效果,而Rg1在降低诱导型一氧化氮合酶的蛋白水平方面比Rb1更有效。此外,尽管Rb1和Rg1处理在修复SAMP8小鼠海马中神经元细胞损失以及抑制星形胶质细胞和小胶质细胞激活方面显示出显著的保护作用,但Rb1比Rg1更有效。这些结果表明,Rb1和Rg1可改善SAMP8小鼠的认知障碍,并且它们在治疗阿尔茨海默病方面具有不同的机制。