Hispidulin: antioxidant properties and effect on mitochondrial energy metabolism.
Hispidulin (6-methoxy-5,7,4'-trihydroxyflavone) and eupafolin (6-methoxy-5,7,3',4'-tetrahydroxyflavone), are flavonoids found in the leaves of Eupatorium litoralle. They have recognized antioxidant and antineoplastic properties, although their action mechanisms have not been previously described. We now report the effects of hispidulin on the oxidative metabolism of isolated rat liver mitochondria (Mit) and have also investigated the prooxidant and antioxidant capacity of both flavonoids. Hispidulin (0.05-0.2 mM) decreased the respiratory rate in state III and stimulated it in state IV, when glutamate or succinate was used as oxidizable substrate. Hispidulin inhibited enzymatic activities between complexes I and III of the respiratory chain. In broken Mit hispidulin (0.2 mM) slightly inhibited ATPase activity (25%). However, when intact Mit were used, the flavonoid stimulated this activity by 100%. Substrate energized mitochondrial swelling was markedly inhibited by hispidulin. Both hispidulin and eupafolin were able to promote iron release from ferritin, this effect being more accentuated with eupafolin with the suggestion of a possible involvement of H2O2 in the process. Hispidulin was incapable of donating electrons to the stable free radical DPPH, while eupafolin reacted with it in a similar way to ascorbic acid. The results indicate that hispidulin as an uncoupler of oxidative phosphorylation, is able to release iron from ferritin, but has distinct prooxidant and antioxidant properties when compared to eupafolin.
Dabaghi-Barbosa
Priscila
P
Departamento de Bioquímica, Universidade Federal do Paraná, CP 19046, Curitiba, PR, CEP 81531-590, Brazil.
Mariante Rocha
Andreia
A
Franco da Cruz Lima
Anderson
A
Heleno de Oliveira
Brás
B
Benigna Martinelli de Oliveira
Maria
M
Gunilla Skare Carnieri
Eva
E
Cadena
Sílvia M S C
SM
Eliane Merlin Rocha
Maria
M
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds; D004734:Energy Metabolism; D005293:Ferritins / Q000737:chemistry; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D005609:Free Radicals / Q000737:chemistry; D066298:In Vitro Techniques; D007501:Iron / Q000737:chemistry; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010851:Picrates / Q000737:chemistry; D051381:Rats
D000975:Antioxidants; D001713:Biphenyl Compounds; D047309:Flavones; D005609:Free Radicals; D016877:Oxidants; D010851:Picrates; D005293:Ferritins; C004931:1,1-diphenyl-2-picrylhydrazyl; D007501:Iron; D000251:Adenosine Triphosphatases; C503624:eupafolin; C055957:hispidulin