Oxidative stress is a common harmful condition of several
neurodegenerative diseases.
Antioxidants represent the medical choice strategy for protection against this unbalanced
oxidant-
antioxidant status. The present study was undertaken to address the role of
kaurane diterpenes foliol,
linearol and sidol in the protection against H(2)O(2)-induced oxidative stress in the human
astrocytoma U373-MG cell line and to establish the underlying mechanisms. U373-MG cells were pretreated with
diterpenes (5 and 10 μM, 24h) prior to H(2)O(2) exposition (1mM, 30 min). We found that
linearol and sidol exerted a significant astroprotective action, and foliol was the least active one.
Linearol and sidol especially increased cell viability as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium
bromide and
lactate dehydrogenase assay and attenuated morphological changes of U373-MG cells induced by H(2)O(2). Moreover, these compounds significantly decreased the level of intracellular
reactive oxygen species, counteracted
glutathione/oxidized glutathione changes, reduced lipid peroxidation and restored
antioxidant and
protein expression of
antioxidant enzymes (
catalase,
superoxide dismutase,
glutathione reductase,
glutathione peroxidase and hemooxigenase-1). Furthermore, these natural products increased Nrf2 nuclear levels, suggesting the activation of this master regulator of antioxidative gene expressions in the protective effect exhibited by the
kaurane diterpenes studied. Collectively, these results suggest that the studied
kaurane diterpenes, mainly
linearol and sidol, protect U373-MG cells from H(2)O(2)-induced injury or degeneration presumably by
antioxidant mechanisms. These compounds may be useful agents for counteracting the oxidative damage occurring during the pathological development of several CNS disorders.