Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells.

Alzheimer's disease (AD) is the most common type of age-related dementia, and causes progressive memory degradation, neuronal loss and brain atrophy. The pathological hallmarks of AD consist of amyloid-β (Aβ) plaque accumulation and abnormal neurofibrillary tangles. Amyloid fibrils are constructed from Aβ peptides, which are recognized to assemble into toxic oligomers and exert cytotoxicity. The fibrillar Aβ-protein fragment 25–35 (Aβ25-35) induces local inflammation, thereby exacerbating neuronal apoptosis. Notoginsenoside R1 (NGR1), one of the primary bioactive ingredients isolated from Panax notoginseng, exhibits effective anti-inflammatory and anti-oxidative activities. However, NGR1 pharmacotherapies targeting Aβ-induced inflammation and cell injury cascade remain to be elucidated. The present study investigated the effect and mechanism of NGR1 in Aβ25-35-treated PC12 cells. NGR1 doses between 250 and 1,000 µg/ml significantly increased cell viability suppressed by 20 µM Aβ25-35 peptide treatment. Notably, the present study demonstrated that Aβ25-35 peptide-induced sphingosine kinase 1 (SphK1) signaling activation was reduced after NGR1 treatment, further inhibiting the downstream NF-κB inflammatory signaling pathway. In addition, administration of SphK1 inhibitor II (SKI–II), a SphK1 inhibitor, also significantly reduced Aβ25-35 peptide-induced apoptosis and the ratio of NF-κB p-p65/p65. Furthermore, SphK1 knockdown in PC12 cells using small interfering RNA alleviated Aβ-induced cell apoptosis and inflammation, suggesting a pivotal role of SphK1 signaling in the anti-inflammatory effect of NGR1. In summary, NGR1 alleviated inflammation and apoptosis stimulated by Aβ25-35 by inhibiting the SphK1/NF-κB signaling pathway and may be a promising agent for future AD treatment. [ABSTRACT FROM AUTHOR]