Clovamide and rosmarinic acid induce neuroprotective effects in in vitro models of neuronal death.
 

Posts


Write a Post
05-27-09 09:24 AM
Anonymous
Clovamide and rosmarinic acid induce neuroprotective effects in in vitro models of neuronal death.
Reply
Related Articles

Clovamide and rosmarinic acid induce neuroprotective effects in in vitro models of neuronal death.

Br J Pharmacol. 2009 May 20;

Authors: Fallarini S, Miglio G, Paoletti T, Minassi A, Amoruso A, Bardelli C, Brunelleschi S, Lombardi G

Background and purpose: Phenolic compounds exert cytoprotective effects; our purpose was to investigate whether the isosteric polyphenolic compounds clovamide and rosmarinic acid are neuroprotective. Experimental approach: Three in vitro models of neuronal death were selected: (i) differentiated SH-SY5Y human neuroblastoma cells exposed to tert-butylhydroperoxide (t-BOOH), for oxidative stress; (ii) differentiated SK-N-BE(2) human neuroblastoma cells treated with L-glutamate, for excitotoxicity; and (iii) differentiated SH-SY5Y human neuroblastoma cells exposed to oxygen-glucose deprivation/reoxygenation, for ischaemia-reperfusion. Cell death was evaluated by lactate dehydrogenase measurements in the cell media, while the mechanisms underlying the effects by measuring: (i) t-BOOH-induced glutathione depletion and increase in lipoperoxidation; and (ii) L-glutamate-induced intracellular Ca(2+) overload (fura-2 method) and inducible gene expression (c-fos, c-jun), by reverse transcriptase-PCR. The ability of compounds to modulate nuclear factor-kappaB and peroxisome proliferator-activated receptor-gamma activation was evaluated by Western blot in SH-SY5Y cells not exposed to harmful stimuli. Key results: Both clovamide and rosmarinic acid (10-100 micromol.L(-1)) significantly protected neurons against insults with similar potencies and efficacies. The EC(50) values were in the low micromolar range (0.9-3.7 micromol.L(-1)), while the maximal effects ranged from 40% to -60% protection from cell death over untreated control at 100 micromol.L(-1). These effects are mediated by the prevention of oxidative stress, intracellular Ca(2+) overload and c-fos expression. In addition, rosmarinic acids inhibited nuclear factor-kappaB translocation and increased peroxisome proliferator-activated receptor-gamma expression in SH-SY5Y cells not exposed to harmful stimuli. Conclusion and implications: Clovamide and rosmarinic acid are neuroprotective compounds of potential use at the nutritional/pharmaceutical interface.

PMID: 19466982 [PubMed - as supplied by publisher]