Ferulic acid alleviates Aß25-35- and lipopolysaccharide-induced PC12 cellular damage: a potential role in Alzheimer's disease by PDE inhibition.

ABSTRACT

OBJECTIVE: Phosphodiesterase (PDE) plays an important role in the pathogenesis of Alzheimer's disease (AD). Ferulic acid (FA) has a therapeutic benefit in the treatment of AD. We investigated whether this therapeutic effect is based on the modulation of the PDE/cyclic adenosine monophosphate (cAMP) pathway. In the present study, we investigated whether FA could abrogate Aß25-35- and lipopolysaccharide-induced cellular damage. MATERIALS AND METHODS: Cell viability, superoxide production, and the levels of inflammatory factors were investigated. We further investigated the intracellular levels of cAMP and Ca2+, both of which are associated with PDE activity. Furthermore, molecular docking was used to identify the binding mode between phosphodiesterase 4B2 (PDE4B2) and FA. RESULTS: Pretreatment with FA significantly maintained cell viability, increased the levels of superoxide dismutase, and inhibited production of TNF-α and IL-1ß induced by Aß25-35. Moreover, pretreatment with FA increased the intracellular levels of cAMP and decreased the intracellular levels of Ca2+. The docking results also showed that FA has the potential to inhibit PDE4B2 activity. CONCLUSIONS: Taken together, our results suggested that one of the therapeutic effects of FA on AD was potentially mediated by modulating the PDE/cAMP pathway.