Journal
ARCHIVES OF PHARMACAL RESEARCH
Volume 29, Issue 8, Pages 699-706Publisher
PHARMACEUTICAL SOC KOREA
DOI: 10.1007/BF02968255
Keywords
hesperetin; hesperidin; neuroprotection; antioxidant; excitotoxicity; beta-amyloid (A(beta))
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The present study evaluated antioxidant and neuroprotective activities of hesperidin, a flavanone mainly isolated from citrus fruits, and its aglycone hesperetin using cell-free bioassay system and primary cultured rat cortical cells. Both hesperidin and hesperetin exhibited similar patterns of 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities. While hesperidin was inactive, hesperetin was found to be a potent antioxidant, inhibiting lipid peroxidation initiated in rat brain homogenates by Fe2+ and L-ascorbic acid. In consistence with these findings, hesperetin protected primary cultured cortical cells against the oxidative neuronal damage induced by H2O2 or xanthine and xanthine oxidase. In addition, it was shown to attenuate the excitotoxic neuronal damage induced by excess glutamate in the cortical cultures. When the excitotoxicity was induced by the glutamate receptor subtype-selective ligands, only the N-methyl-D-aspartic acid-induced toxicity was selectively and markedly inhibited by hesperetin. Furthermore, hesperetin protected. cultured cells against the A(beta(25-35))-induced neuronal damage. Hesperidin, however, exerted minimal or no protective effects on the neuronal damage tested in this study. Taken together, these results demonstrate potent antioxidant and neuroprotective effects of hesperetin, implying its potential role in protecting neurons against various types of insults associated with many neurodegenerative diseases.
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