Diterpenoids isolated from Sideritis species protect astrocytes against oxidative stress via Nrf2

Andalusol (1), conchitriol (2), and lagascatriol (3) are diterpenoids produced by Sideritis species. Hydrogen peroxide-induced oxidative stress in U373-MG cells was used as an in vitro model to evaluate the cytoprotective potential, based on antioxidant properties, of these isolated compounds and to investigate the underlying mechanisms. Experimental results revealed that pretreatment with compounds 1 and 3 restored H₂O₂-induced oxidative changes by increasing cell viability, attenuating morphological changes, inhibiting intracellular ROS production and lipid peroxidation, and enhancing the antioxidant defense system. Furthermore, nuclear factor E2-related factor 2 (Nrf2) signaling was involved in the protective mechanisms of 1-3. The present findings suggest that two of the compounds studied (1 and 3) might play a preventive role in neurodegenerative diseases associated with oxidative stress.