Neuroprotective effects of the citrus flavanones against H2O2-induced cytotoxicity in PC12 cells.
The citrus flavanones hesperidin, hesperetin, and neohesperidin are known to exhibit antioxidant activities and could traverse the blood-brain barrier. H2O2 formation induces cellular oxidative stress associated with neurodegenerative diseases. In this study, protective effects of pretreatments (6 h) with hesperidin, hesperetin, and neohesperidin (0.8, 4, 20, and 50 microM) on H2O2-induced (400 microM, 16 h) neurotoxicity in PC12 cells were evaluated. The results showed that hesperetin, hesperidin, and neohesperidin, at all test concentrations, significantly ( p < 0.05) inhibited the decrease of cell viability (MTT reduction), prevented membrane damage (LDH release), scavenged ROS formation, increased catalase activity, and attenuated the elevation of intracellular free Ca2+, the decrease of mitochondrial membrane potential (except those of 0.8 microM neohesperidin-treated cells) and the increase of caspase-3 activity in H2O2-induced PC12 cells. Meanwhile, hesperidin and hesperetin attenuated decreases of glutathione peroxidase and glutathione reductase activities and decreased DNA damage in H2O2-induced PC12 cells. These results first demonstrate that the citrus flavanones hesperidin, hesperetin, and neohesperidin, even at physiological concentrations, have neuroprotective effects against H2O2-induced cytotoxicity in PC12 cells. These dietary antioxidants are potential candidates for use in the intervention for neurodegenerative diseases.
Hwang
Sam-Long
SL
Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
Yen
Gow-Chin
GC
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002957:Citrus / Q000737:chemistry*; D004249:DNA Damage / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D044950:Flavanones; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D053148:Caspase 3; D020782:Matrix Metalloproteinases; D002118:Calcium