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

Abstract

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 Panaxnotoginseng, 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 1,000µg/ml significantly increased cell viability suppressed by 20µM 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.