Ginsenoside RK1 improves cognitive impairments and pathological changes in Alzheimer's disease via stimulation of the AMPK/Nrf2 signaling pathway

作者：Lingyu She, Jinfeng Sun, Xiong Li, Ankang Li, Liwei Li, Haibin Wu, Juan Ren, Wei Wang, Guang Liang, Xia Zhao · 发表于：Phytomedicine · 年份：2023 · DOI：10.1016/j.phymed.2023.155168 · 被引用次数：65 · 研究领域：Genomics, phytochemicals, and oxidative stress、Metabolism, Diabetes, and Cancer、Alzheimer's disease research and treatments

BACKGROUND: The pathogenesis of Alzheimer's disease (AD) is complex, resulting in unsatisfactory effects of single-target therapeutic drugs. Accumulation evidence suggests that low toxicity multi-target drugs may play effective roles in AD. Ginseng is the root and rhizome of Panax ginseng Meyer, which can be used not only as herbal medicine but also as a functional food to support body functions. Ginsenoside RK1 (RK1), obtained from ginseng plants through high-temperature treatment, has antiapoptotic, antioxidant, anti-inflammatory effects and these events are involved in the development of AD. So, we believe that RK1 may be an effective drug for the treatment of AD. HYPOTHESIS/PURPOSE: We aimed to investigate the potential protective effects and mechanisms of RK1 in AD. METHODS: Neuronal damage was detected by MTT assay, LDH assay, immunofluorescence and western blotting. Oxidative stress was measured by JC-1 staining, reactive oxygen species (ROS) staining, superoxide dismutase (SOD) and malonaldehyde (MDA). The cognitive deficit was measured through morris water maze (MWM) and novel object recognition (NOR) tests. RESULTS: RK1 attenuated Aβ-induced apoptosis, restored mitochondrial membrane potential (ΔΨm), and reduced intracellular levels of ROS in both PC12 cells and primary cultured neurons. In vivo, RK1 significantly improved cognitive deficits and mitigated AD-like pathological features. Notably, RK1 demonstrated superior efficacy compared to the positive control drug...