Affiliations: [a] Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital ofChongqing Medical University, Chongqing, China | [b] Chongqing Key Laboratory of TranslationalMedical Research in Cognitive Development and Learning and Memory Disorders, Children’s Hospital of ChongqingMedical University, Chongqing, China | [c] Brain Research Centre, University of British Columbia, Vancouver, BC, Canada
Correspondence:
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Correspondence to: Zhifang Dong, Professor, PhD, 136 Zhongshan Er Road, Yuzhong District, Chongqing 400014, PR China. Tel.: +0086 23 63637857; Fax: +0086 23 63633751; E-mail zfdong@aliyun.com
Note: [1] These authors have contributed equally to this work.
Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the deposition of amyloid-β peptides (Aβ). Aβ accumulation leads to the formation of neurofibrillary tangles, inflammation, axonal injury, synapse loss, and neuronal apoptosis. Thus, reducing Aβ levels should exert a neuroprotective effect against AD. Ginsenoside Rf, an extract from Panax notoginseng, has potent anti-fatigue, anti-nociception, anti-oxidation, and anti-inflammation properties. However, it is unclear whether ginsenoside Rf is effective in the treatment of AD. Here, we reported that ginsenoside Rf could significantly attenuate Aβ-induced apoptosis in N2A cells, as reflected by a dramatic increase in mitochondrial membrane potential and decrease in Ca2 + concentration, reactive oxygen species, and active caspase-3 expression. Meanwhile, ginsenoside Rf could alleviate the Aβ-induced inflammation reaction, such as the decrease of interferon-gamma (IFN-γ) and active caspase-1 expression and the increase of interleukin-13. Furthermore, we also found that Rf is able to accelerate Aβ clearance and subsequently reduces Aβ level in N2A cells stably transfected with human Swedish mutant APP695 (N2A-APP). More importantly, daily Rf treatment (20 mg/kg, i.p.) throughout the experiment dramatically improved spatial learning and memory in Aβ42-induced mouse model of AD. Taken together, these results indicate that ginsenoside Rf may decrease Aβ-induced neurotoxicity and memory decline via anti-inflammatory response during AD development, suggesting that Rf may be a potential therapeutic agent for treating AD.
