RESUMO
Oxidative stress is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Natural products are considered as therapeutically useful antioxidant agents against reactive oxygen species (ROS). We have evaluated the antioxidant and protective potential of the monoterpenes 1,8-cineole and α-pinene against H2O2-induced oxidative stress in PC12 (rat pheochromocytoma) cells. Pretreatment with these monoterpenes was found to attenuate the loss of cell viability and the changes in cell morphology. Moreover, they inhibited the intracellular ROS production and markedly enhanced the expression of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and heme-oxygenase 1 (HO-1). In addition, they were able to decrease apoptosis as is evident from reduced capase-3 activity. The mechanisms of their antioxidant action appear to involve ROS scavenging and induction of the nuclear Nrf2 factor. This study demonstrates the potential beneficial therapeutic effect of these common monoterpenes on the oxidant/antioxidant balance in diseases of the nervous system.
Assuntos
Cicloexanóis/farmacologia , Peróxido de Hidrogênio/toxicidade , Monoterpenos/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Monoterpenos Bicíclicos , Western Blotting , Caspase 3/metabolismo , Catalase/metabolismo , Cicloexanóis/química , Eucaliptol , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Monoterpenos/química , Fármacos Neuroprotetores/química , Oxidantes/toxicidade , Células PC12 , Feocromocitoma/metabolismo , Feocromocitoma/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Salvia lavandulifolia Vahl., known as "Spanish sage", has potential value in dementia for its sedative, antioxidant, anti-inflammatory and anticholinesterase properties. This work aimed to evaluate the in vitro neuroprotective activity of S. lavandulifolia essential oils, obtained from plants at different phenological stages (vegetative and flowering phases) and plants grown at different densities, against H2O2-induced oxidative stress in PC12 cells. The effect on cell viability and morphology, lipid peroxidation, GSH/GSSG ratio, intracellular ROS levels, antioxidant enzymes (CAT, SOD, GR, GPx, HO-1) and apoptotic enzymes was investigated. Comparing with H2O2-treated PC12 cells, pretreatments with essential oil samples attenuated morphological changes and loss of cell viability, decreased MDA levels and intracellular ROS production and increased GSH/GSSG ratio. Moreover, Spanish sage increased antioxidant status as evidenced in an increase of antioxidant enzyme activity and protein expression and inhibited caspase-3 activity. Furthermore, our results suggest that S. lavandulifolia essential oils are able to activate Nrf2 transcription factor. Collectively, the sample of essential oil obtained with the highest densities of planting and at flowering phase exerted the major neuroprotective activity. Our findings demonstrate that S. lavandulifolia essential oils may have therapeutic value for the prevention and treatment of neurodegenerative diseases associated with oxidative stress-induced neuronal injury.
