Neuroprotective mechanism of Ribisin A on Aβ25-35-induced PC12 cell damage model.

Amyloid-β (Aβ) is a neurotoxic substance, and studies have found that its excessive deposition in the brain, forming senile plaques, is a major pathological feature of Alzheimer's disease (AD). In previous studies, Ribisin A, a benzofuran compound, was purified from Phellinus ribis and found to have neuroprotective effects. This study aims to elucidate the neuroprotective mechanism of Ribisin A in an Aβ25-35-damaged PC12 cell model. This study established an in vitro AD model using PC12 cells damaged by Aβ25-35. We applied methyl tetrazolium (MTT), enzyme-linked immunosorbent assay (ELISA) kits, flow cytometry, and western blotting techniques to study the effects of Ribisin A on the Aβ25-35 injury model and the relationship with the ERK pathway from the aspects of cell injury degree, cytokine content, Calcium ion (Ca2 +) concentration, mitochondrial membrane potential (MMP), and the ERK pathway-related protein expression. Results indicate that Ribisin A reduced lactate dehydrogenase (LDH), reactive oxygen species (ROS), tumour necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels in the Aβ25-35-induced cellular injury model while increasing superoxide dismutase (SOD) levels. Furthermore, it inhibited Aβ25-35-induced increases in Ca²⁺ concentration and decreases in MMP, leading to upregulation of ERK pathway-related proteins TrkB, p-ERK1/2, and p-CREB, with significant elevations in p-ERK/ERK and p-CREB/CREB ratios (P < 0.01). Ribisin A can reduce oxidative damage, inhibit inflammation, restore mitochondrial function, and reduce apoptosis. The neuroprotective mechanism of Ribisin A may involve regulation of the TrkB-mediated ERK/CREB signaling cascade. Our study provides evidence for the neuroprotective mechanism of Ribisin A in an Aβ25-35-induced cellular injury model.