The Spice Sage and Its Active Ingredient Rosmarinic Acid Protect PC12 Cells from Amyloid-β Peptide-Induced Neurotoxicity

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Abstract
Traditional use and clinical reports suggest that the culinary herb sage (Salvia officinalis) may be effective for patients with mild to moderate Alzheimer9s disease (AD). In this study, we evaluated the effect of a standardized extract from the leaves of S. officinalis (SOE) and its active ingredient rosmarinic acid on Alzheimer amyloid-β peptide (Aβ)-induced toxicity in cultured rat pheochromocytoma (PC12) cells. Incubation of PC12 cells with Aβ (fragment 1–42) for 24 h caused cell death, and this effect was reduced by SOE and its active ingredient, rosmarinic acid. Rosmarinic acid reduced a number of events induced by Aβ. These include reactive oxygen species formation, lipid peroxidation, DNA fragmentation, caspase-3 activation, and tau protein hyperphosphorylation. Moreover, rosmarinic acid inhibited phosphorylated p38 mitogen-activated protein kinase but not glycogen synthase kinase 3β activation. These data show the neuroprotective effect of sage against Aβ-induced toxicity, which could validate the traditional use of this spice in the treatment of AD. Rosmarinic acid could contribute, at least in part, for sage-induced neuroprotective effect.