P -coumaric acid and ursolic acid from corni fructus attenuated β-amyloid_25-35-induced toxicity through regulation of the NF-κB signaling pathway in PC12 cells

Neuroinflammatory responses induced by amyloid-beta peptide (Aβ) are important causes in the pathogenesis of Alzheimers disease (AD). Blockade of Aβ has emerged as a possible therapeutic approach to control the onset of AD. This study investigated the neuroprotective effects and molecular mechanisms of p-coumaric acid (p-CA) and ursolic acid (UA) from Corni fructus against Aβ_25-35-induced toxicity in PC12 cells. p-CA and UA significantly inhibited the expression of iNOS and COX-2 in Aβ _25-35-injured PC12 cells. Blockade of nuclear translocation of the p65 subunit of nuclear factor κB (NF-κB) and phosphorylation of IκB- was also observed after p-CA and UA treatment. For the upstream kinases, UA exclusively reduced ERK1/2, p-38, and JNK phosphorylation, but p-CA suppressed ERK1/2 and JNK phosphorylation. Both compounds comprehensively inhibited NF-κB activity, but possibly with different upstream pathways. The results provide new insight into the pharmacological modes of p-CA and UA and their potential therapeutic application to AD.