Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Affiliated TCM Hospital/School of Pharmacy/Sino-Portugal TCM International Cooperation Center, Southwest Medical University, Luzhou, 646000, China.
Behav Brain Res. 2021 May 7;405:113146. doi: 10.1016/j.bbr.2021.113146. Epub 2021 Feb 2.
Ginsenoside Rb1 (Rb1) is one of the most active components found in ginseng and provides important benefits to the central nervous system, especially for the improvement of learning and memory. Previous studies demonstrated that Rb1 protected against scopolamine-induced amnesia and exhibited memory-enhancing effects in the SAMP8 mouse model. However, the effects of Rb1 against chronic restraint stress (CRS)-induced cognitive impairments, especially the role of Rg1 on the performance of reward directed instrumental conditioning have not been investigated. In this study, rats were subjected to CRS (6 h/day) for 28 days. Thereafter, behavioural tests including reward-directed instrumental conditioning task (RICT) and the Morris water maze (MWM) task were conducted. Administered of Rb1 (6.75 and 13.5 mg/kg, i.p.) remarkably ameliorated the memory impairments caused by CRS as evident from the results of RICT and MWM task, and this effect was accompanied by noticeable alterations in the levels of oxidative markers (superoxide dismutase, catalase, and lipid peroxidation) in the hippocampus. Additionally, Rb1 reduced the ratio of Bax:Bcl-2 and the expression of cleaved caspase-3 and cleaved caspase-9, increased the levels of synaptophysin (SYP) and postsynaptic density 95 (PSD95) and activated the BDNF/TrkB pathway in the hippocampus. In summary, the present study demonstrated that Rb1 rescues cognitive deficits induced by CRS is partially mediated by antagonizing oxidative stress and apoptosis, improving synaptic plasticity and restoring the BDNF/TrkB signalling pathway. This newly discovered effect of Rb1 sheds light on its applications in the development of therapeutic interventions to alleviate the deleterious effects of chronic stress.
人参皂苷 Rb1(Rb1)是人参中最活跃的成分之一,对中枢神经系统有重要益处,尤其对学习和记忆有改善作用。先前的研究表明,Rb1 可预防东莨菪碱诱导的健忘症,并在 SAMP8 小鼠模型中表现出增强记忆的作用。然而,Rb1 对慢性束缚应激(CRS)诱导的认知障碍的作用,特别是 Rg1 对奖赏导向的工具性条件反射表现的影响尚未被研究。在这项研究中,大鼠接受 CRS(每天 6 小时)处理 28 天。此后,进行了行为测试,包括奖赏导向的工具性条件反射任务(RICT)和 Morris 水迷宫(MWM)任务。腹腔注射 Rb1(6.75 和 13.5 mg/kg)可显著改善 CRS 引起的记忆障碍,这从 RICT 和 MWM 任务的结果中可以明显看出,并且这种作用伴随着海马氧化标记物(超氧化物歧化酶、过氧化氢酶和脂质过氧化)水平的明显改变。此外,Rb1 降低了 Bax:Bcl-2 的比值和 cleaved caspase-3 和 cleaved caspase-9 的表达,增加了突触小体蛋白(SYP)和突触后密度 95(PSD95)的水平,并激活了海马中的 BDNF/TrkB 信号通路。总之,本研究表明,Rb1 部分通过拮抗氧化应激和凋亡、改善突触可塑性和恢复 BDNF/TrkB 信号通路来挽救 CRS 诱导的认知缺陷。Rb1 的这种新发现的作用为其在开发治疗干预措施以减轻慢性应激的有害影响方面的应用提供了新的思路。