p-Coumaric Acid and Ursolic Acid from Corni fructus Attenuated β-Amyloid25-35-Induced Toxicity through Regulation of the NF-κB Signaling Pathway in PC12 Cells

Neuroinflammatory responses induced by amyloid-beta peptide (A beta) are important causes in the pathogenesis of Alzheimer's disease (AD). Blockade of A beta 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 Cori fructus against A beta(25-35)-induced toxicity in PC12 cells. p-CA and UA significantly inhibited the expression of iNOS and COX-2 in A beta(25-35)-injured PC12 cells. Blockade of nuclear translocation of the p65 subunit of nuclear factor kappa B (NF-kappa B) and phosphorylation of I kappa B-alpha 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-kappa B 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.