Quercetin, kaempferol and biapigenin from Hypericum perforatum are neuroprotective against excitotoxic insults.
In the present study we investigated the effects of phenolic compounds present in Hypericum perforatum against neuronal excitotoxicity and mitochondrial dysfunction. Quercetin, kaempferol and biapigenin significantly reduced neuronal death caused by 100 microM kainate plus 100 microM N-methyl-D-aspartate. The observed neuroprotection was correlated with prevention of delayed calcium deregulation and with the maintenance of mitochondrial transmembrane electric potential. The three compounds were able to reduce mitochondrial lipid peroxidation and loss of mitochondrial transmembrane electric potential caused by oxidative stress induced by ADP plus iron. Moreover, biapigenin was also able to significantly affect mitochondrial bioenergetics and decrease the capacity of mitochondria to accumulate calcium. Taken together, the results suggest that the neuroprotective action induced by quercetin and kaempferol are mainly mediated by antioxidant effects, whereas biapigenin mainly affects mitochondrial bioenergetics and calcium uptake.
Silva
Bruno
B
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Oliveira
Paulo J
PJ
Dias
Alberto
A
Malva
Joao O
JO
D000704:Analysis of Variance; D000818:Animals; D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology; D020902:Hypericum / Q000737:chemistry*; D044949:Kaempferols / Q000737:chemistry / Q000494:pharmacology; D007608:Kainic Acid / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D044946:Biflavonoids; D018690:Excitatory Amino Acid Agonists; D044949:Kaempferols; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; C446502:biapigenin; D016202:N-Methylaspartate; C006552:kaempferol; D047310:Apigenin; D011794:Quercetin; D007608:Kainic Acid; D002118:Calcium