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

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles.
• Aβ peptides, particularly the Aβ25-35 fragment, induce inflammation and neuronal apoptosis, contributing to AD pathogenesis.
• Notoginsenoside R1 (NGR1), derived from Panax notoginseng, possesses anti-inflammatory and antioxidant properties, but its role in Aβ-induced neurotoxicity is unclear.

Purpose of the Study:

• To investigate the therapeutic effects of NGR1 on Aβ25-35-induced inflammation and apoptosis in PC12 cells.
• To elucidate the underlying molecular mechanisms, focusing on the sphingosine kinase 1 (SphK1)/NF-κB signaling pathway.

Main Methods:

• PC12 cells were treated with Aβ25-35 peptide to induce cellular damage and inflammation.
• The effects of varying NGR1 concentrations on cell viability were assessed.
• SphK1 signaling activation, NF-κB pathway, and apoptosis markers were analyzed following NGR1 treatment.
• Pharmacological inhibition and genetic knockdown of SphK1 were employed to confirm its role.

Main Results:

• NGR1 significantly enhanced cell viability in Aβ25-35-treated PC12 cells.
• NGR1 treatment suppressed Aβ25-35-induced activation of SphK1 signaling and downstream NF-κB inflammatory pathway.
• Inhibition or knockdown of SphK1 mimicked NGR1's protective effects, reducing apoptosis and inflammation.

Conclusions:

• NGR1 demonstrates neuroprotective effects against Aβ25-35-induced toxicity by inhibiting the SphK1/NF-κB signaling pathway.
• NGR1 represents a potential therapeutic agent for Alzheimer's disease, targeting key inflammatory and apoptotic pathways.