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Alzheimer's disease (AD) is known to be caused by accumulation of amyloid-β peptide (Aβ).Aβ leads to learning and memory impairment in rats,but it is improved by H2S donor i.e.by sodium hydrosulfide (NaHS).However, the underlying mechanism is not clear.This study was designed to investigate whether NaHS could improve the inflammation and apoptosis induced by Aβ.It is found that NaHS could attenuate Aβ25-35-induced neurons reduction, apoptosis, and inhibit the activation of pro-caspase-3 and decrease protein content of PDE 5 in the hippocampus of the rats.It also up-regulated the expression of PPAR-α and PPAR-γ, but it did not affect the PPAR-β.Moreover, Aβ25-35-treated rats displayed the decrease of IκB-α degradation and the increase of NF -κB p65 phosphorylation, whereas these were reversed by NaHS.Our data suggest that NaHS prevents Aβ-induced neurotoxicity by up-regulation of PPAR-α, PPAR-γ and by inhibition of PDE 5.Hence NaHS might be beneficial to treat AD.