Proanthocyanidins improves lead-induced cognitive impairments by blocking endoplasmic reticulum stress and nuclear factor-κB-mediated inflammatory pathways in rats

• This study found a novel role for proanthocyanidins against Pb-induced neurotoxicity.
• Proanthocyanidins improved cognitive dysfunction induced by Pb in rats.
• Proanthocyanidins decreased the levels of β-amyloid and phosphorylated tau in brains.
• Proanthocyanidins inhibited oxidative stress and ER stress in Pb-exposed rats.
• Proanthocyanidins inhibited brain inflammation by reducing NF-κB activation in rats.

Proanthocyanidins (PCs), a class of naturally occurring flavonoids, had been reported to possess a variety of biological activities, including anti-oxidant, anti-tumor and anti-inflammatory. In this study, we examined the protective effect of PCs against lead-induced inflammatory response in the rat brain and explored the potential mechanism of its action. The results showed that PCs administration significantly improved behavioral performance of lead-exposed rats. One of the potential mechanisms was that PCs decreased reactive oxygen species production and increased the total antioxidant capacity in the brains of lead-exposed rats. Furthermore, the results also showed that PCs significantly decreased the levels of tumor necrosis factor-α, interleukin 1β and cyclooxygenase-2 in the brains of lead-exposed rats. Moreover, PCs significantly decreased the levels of beta amyloid and phosphorylated tau in the brains of lead-treated rats, which in turn inhibited endoplasmic reticulum (ER) stress. PCs also decreased the phosphorylation of protein kinase RNA-like ER kinase, eukaryotic translation initiation factor-2, inositol-requiring protein-1, c-Jun N-terminal kinase, p38 and inhibited nuclear factor-κB nuclear translocation in the brains of lead-exposed rats. In conclusion, these results suggested that PCs could improve cognitive impairments by inhibiting brain oxidative stress and inflammatory response.

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