Celastrol alleviates angiotensin II-mediated vascular smooth muscle cell senescence via induction of autophagy

Reactive oxygen species (ROS) production has been implicated in the promotion of cellular senescence. Celastrol, a quinone methide triterpenoid isolated from the Celastraceae family, exerts antioxidant effects and enhances autophagy in various cell types. Since autophagy serves an important role in regulating ROS, it was hypothesized that the antioxidant effect of celastrol is via enhanced autophagy, thus inhibiting cell senescence. Therefore, the present study used a Senescence beta-Galactosidase Staining kit, western blot analysis and cell cycle analysis to investigate whether celastrol alleviates angiotensin (Ang) II-induced cellular senescence by upregulating autophagy in vascular smooth muscle cells (VSMCs). The results demonstrated that celastrol reduced Ang II-induced senescence of VSMCs. Ang II-induced generation of ROS and the subsequent VSMC senescence were counteracted by pretreatment with celastrol, determined by a ROS assay kit. Celastrol significantly upregulated VSMC autophagy, which reduced intracellular ROS and the subsequent cellular senescence induced by Ang II. Furthermore, celastrol markedly suppressed activity of the mechanistic target of rapamycin signaling pathway in VSMCs. In conclusion, the present study demonstrated that celastrol counteracts VSMC senescence probably by reducing ROS production via activation of autophagy, which may hold promise for the prevention and treatment of aging-associated cardiovascular disorders such as atherosclerosis.