Protocatechuic acid improves cognitive deficits and attenuates amyloid deposits, inflammatory response in aged AβPP/PS1 double transgenic mice

Abstract

Protocatechuic acid (PCA), a phenolic compound of Radix Salviae Miltiorrhizae (RSM), has been found to have a protective effect on improving cognitive deficits in STZ-induced AD rats. The present study aimed to evaluate the potential protection activity of PCA on improving cognitive deficits and attenuating Aβ deposition and inflammatory responses in aged AβPP/PS1 double transgenic AD-model mice. The results of Morris water maze test showed that PCA (100mg/kg) significantly prolonged the mean latency time and the path length of AβPP/PS1 mice. PCA could significantly reduce the number of Aβ positive expressions in the hippocampus and cerebral cortex of AβPP/PS1 mice by immunocytochemical assay with Congo red staining and decrease remarkably APP expression level by Western blot analysis (P<0.01). The results from ELISA and Western blot analysis showed that the levels of inflammatory cytokines including TNF-α, IL-1β, IL-6 and IL-8 decreased remarkably by the treatment with PCA (P<0.01). Further, there was a substantial increase of brain derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex of AβPP/PS1 mice treated with PCA (P<0.01). The present study provided confirmatory evidence that PCA significantly decreased Aβ deposits, APP and inflammatory response, whereas increased learning and memory ability, as well as enhanced BDNF level. Our findings indicated that PCA is an effective neuroprotective agent for AD therapy. It might be associated with the attenuation on Aβ deposits and inflammation responses involved in the process.