Cytoprotective effects of geraniin against peroxynitrite- and peroxyl radical-induced cell death via free radical scavenging activity

The role of natural antioxidants in combating the deleterious effects of free radicals has received much attention. In the present study, the cytoprotective effects and the free radical scavenging activity of geraniin, a hydrolysable ellagitannin from Nephelium lappaceum rind, were evaluated by using various approaches. Addition of geraniin to the culture media resulted in a profound cytoprotective effect against damages induced by the peroxynitrite generator 3-morpholinosydnonimine (SIN-1), and the peroxyl radical generator 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH). Geraniin exhibits more potent cytoprotective activity than that of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Geraniin exhibited potent antioxidant activity against reactive species, such as nitric oxide, superoxide anion, and chemically synthesized peroxynitrite. Kinetic analysis of reactivity against peroxyl radicals generated by AAPH revealed that geraniin possesses potent reactivity against peroxyl radicals with higher stoichiometric number than Trolox. The cytoprotective effect of geraniin was only observed when geraniin and these toxic compounds were co-existing, suggesting that geraninn exhibits cytoprotective effects via free radical scavenging activity in the extracellular fluid.