Proanthocyanidin B2 attenuates high-glucose-induced neurotoxicity of dorsal root ganglion neurons through the PI3K/Akt signaling pathway

Abstract

High glucose affects primary afferent neurons in dorsal root ganglia by inhibiting neurite elongation, causing oxidative stress, and inducing neuronal apoptosis and mitochondrial dysfunction, which finally result in neuronal damage. Proanthocyanidin, a potent antioxidant, has been shown to have neuroprotective effects. Proanthocyanidin B2 is a common dimer of oligomeric proanthocyanidins. To date, no studies have reported the neuroprotective effects of proanthocyanidin B2 against high-glucose-related neurotoxicity in dorsal root ganglion neurons. In this study, 10 µg/mL proanthocyanidin B2 was used to investigate its effect on 45 mM high-glucose-cultured dorsal root ganglion neurons. We observed that challenge with high levels of glucose increased neuronal reactive oxygen species and promoted apoptosis, decreased cell viability, inhibited outgrowth of neurites, and decreased growth-associated protein 43 protein and mRNA levels. Proanthocyanidin B2 administration reversed the neurotoxic effects caused by glucose challenge. Blockage of the phosphatidylinositol 3 kinase/Akt signaling pathway with 10 µM LY294002 eliminated the protective effects of proanthocyanidin B2. Therefore, proanthocyanidin B2 might be a potential novel agent for the treatment of peripheral diabetic neuropathy.

Keywords

• nerve regeneration; high glucose; diabetes; neurons; neuropathy; reactive oxygen species; apoptosis; growth-associated protein 43; cell viability; neural regeneration