title: Hispidulin: antioxidant properties and effect on mitochondrial energy metabolism.
abstract: 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.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Paraná, CP 19046, Curitiba, PR, CEP 81531-590, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: Dabaghi-Barbosa
authors.forename: Andreia
authors.initials: A
authors.lastname: Mariante Rocha
authors.forename: Anderson
authors.initials: A
authors.lastname: Franco da Cruz Lima
authors.forename: Brás
authors.initials: B
authors.lastname: Heleno de Oliveira
authors.forename: Maria
authors.initials: M
authors.lastname: Benigna Martinelli de Oliveira
authors.forename: Eva
authors.initials: E
authors.lastname: Gunilla Skare Carnieri
authors.forename: Sílvia M S C
authors.initials: SM
authors.lastname: Cadena
authors.forename: Maria
authors.initials: M
authors.lastname: Eliane Merlin Rocha
mesh_terms: 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
chemical_list: 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