title: Kaurane diterpenes from Sideritis spp. exert a cytoprotective effect against oxidative injury that is associated with modulation of the Nrf2 system.
abstract: Kaurane diterpenes have been shown to possess antioxidant properties. As a part of our ongoing studies on the identification of biologically active diterpenes from Sideritis spp., we have previously isolated and structurally elucidated the major kaurane diterpenes foliol, linearol and sidol, in a previous study from the aerial parts of Sideritis linearifolia and Sideritis leucantha. We have now examined the ability of these compounds to protect PC12 cells in an H2O2-induced oxidative stress model. Linearol and sidol (5 and 10 μM, 24 h) significantly attenuated loss of mitochondrial function (MTT assay) and membrane integrity (LDH assay) and morphological changes associated with H2O2-mediated cytotoxicity. Moreover, pretreatments with linearol and sidol effectively reduced intracellular ROS production, decreased MDA levels (lipid peroxidation product) and restored GSH/GSSG ratio. Furthermore, analysis of the effect of diterpenes on antioxidant enzymes showed that linearol and sidol induced the upregulation and protein expression of the main antioxidant enzymes CAT, SOD, GPx, GR and HO-1. Considering molecular mechanisms for maintaining cellular redox homeostasis by linearol and sidol, it would appear that the Nrf2 transcription factor seems to be involved. These results indicate that linearol and sidol are potential cytoprotective compounds, through antioxidant mechanisms, under H2O2-induced oxidative stress.
authors: Department of Pharmacology, Faculty of Pharmacy, University Complutense, Madrid, Spain.
authors: E
authors: E
authors: González-Burgos
authors: M E
authors: ME
authors: Carretero
authors: M P
authors: MP
authors: Gómez-Serranillos
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008968:Molecular Conformation; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D031365:Sideritis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D045786:Diterpenes, Kaurane; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D010936:Plant Extracts; D006861:Hydrogen Peroxide
keywords: 2′,7′-dichlorofluorescin diacetate; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; CAT; DCFH-DA; DMSO; GPx; GR; GSH; GSSG; HO-1; Hydrogen peroxide; Kaurane diterpenes; MTT; Nrf2; Oxidative stress; PC12 cells; ROS; SOD; Sideritis; catalase; dimethylsulfoxide; glutathione; glutathione peroxidase; glutathione reductase; hemeoxygenase-1; nuclear factor-erythroid 2; oxidized glutathione; reactive oxygen species; superoxide dismutase