Epidemiological studies suggest that nutritional antioxidants may reduce the incidence of neurodegenerative disorders and age-related cognitive decline. Specifically, protection against oxidative stress and inflammation has served as a rationale for promoting diets rich in vegetables and fruits. The present study addresses secretory phospholipase A(2) (sPLA(2)) as a novel candidate effector of neuroprotection conferred by anthocyanins and anthocyanidins. Using a photometric assay, 15 compounds were screened for their ability to inhibit PLA(2). Of these, cyanidin, malvidin, peonidin, petunidin, and delphinidin achieved K(i) values <or=18 microM, suggesting a modulatory role for berry polyphenols in phospholipid metabolism.