title: Mitochondrial-targeted protective properties of isolated diterpenoids from sideritis spp. in response to the deleterious changes induced by H2O2.
abstract: Mitochondrial impairment and oxidative stress are considered widely to be central events in many forms of neurodegenerative disease. The current study has evaluated for the first time the potential protective role of three diterpenoids [andalusol (1), conchitriol (2), and lagascatriol (3)] in response to the deleterious H2O2-induced changes on mitochondrial function. U373-MG human astrocytoma cells and PC12 rat adrenal pheochromocytoma cells were used as models for evaluating the cytoprotective potential of these compounds. In the absence of diterpenoids 1-3, H2O2 compromised mitochondrial function, decreasing mitochondrial membrane potential and ATP levels, increasing caspase-3 activity, and disrupting cytosolic and mitochondrial calcium homeostasis. However, treatment with the diterpenoids, prior to H2O2, prevented these mitochondrial perturbations. In particular, 1 and 3 were the most effective compounds in protecting mitochondrial function against H2O2-induced oxidative stress in U373-MG, whereas all three diterpenoids studied were significantly active against PC12 cells. Since consistent evidence has demonstrated the contribution of H2O2 on both progression and pathological development of several human diseases associated with mitochondrial function and oxidative stress responses, compounds 1-3 are worthy of further investigation.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Complutense University, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: González-Burgos
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Duarte
authors.forename: Maria Emilia
authors.initials: ME
authors.lastname: Carretero
authors.forename: Paula Isabel
authors.initials: PI
authors.lastname: Moreira
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Gómez-Serranillos
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000032:analysis; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000494:pharmacology; D031365:Sideritis / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D004224:Diterpenes; D017382:Reactive Oxygen Species; C577707:conchitriol; C110596:ent-13(16),14-labdadiene-6,8,18-triol; C577706:lagascatriol; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D053148:Caspase 3; D002118:Calcium