Kaurane diterpenes as mitochondrial alterations preventive agents under experimental oxidative stress conditions

Foliol, linearol, and sidol are the most common diterpenes found in Sideritis L. spp. (Lamiaceae) with a wide range of demonstrated properties including anti-inflammatory, antioxidant, and anti-apoptotic effects.

For the first time, the present work was studied for the potential protective role of these kaurane-type diterpenes on mitochondrial oxidative stress induced by H2O2 in the human astrocytoma U373-MG cell line and in the rat adrenal pheochromocytoma PC12 cell line.

Mitochondrial protection was assayed at 5 and 10 µM concentrations for 24 h (for kaurane diterpenes) and H2O2 as oxidative stress inducer (0.1 mM for PC12 cells and 1 mM for U373-MG, for 30 min). ATP concentration was determined by high-performance liquid chromatography (HPLC), and changes in mitochondrial membrane potential, caspase-3 activity as well as in cytosolic and mitochondrial calcium levels were assessed by fluorometric techniques, by using specific fluorescent probes.

Pretreatments for 24 h with linearol and sidol, prior to H2O2 exposure, acted as mitochondrial alterations preventive agents by increasing membrane potential (over 40-60% in PC12 cells and over 10-20% in U373-MG), restoring both cytosolic and mitochondrial calcium homeostasis (linearol at 10 µM caused a 3.5-fold decrease in cytosolic calcium concentration in PC12 cells), decreasing caspase-3 activity (over 1.25-1.5-fold for linearol and sidol) and avoiding ATP depletion (linearol increased over 20% ATP level in both cell types).

Our results suggest that linearol and sidol could provide protective activity by targeting mitochondria in response to the deleterious changes induced by H2O2.