Astragaloside IV alleviates senescence of vascular smooth muscle cells through activating Parkin-mediated mitophagy.

Abstract

Astragaloside IV (AS-IV), as one of the main active components of Astragalus membranaceus, has been reported to have cardiovascular protective effects. However, the role and molecular mechanism of AS-IV in vascular senescence have not been clearly stated. The in vitro aging model was constructed using bleomycin (BLM) in vascular smooth muscle cells (VSMCs). Cell senescence were assessed through Western blotting analysis of aging markers, flow cytometry, and the β-galactosidase (SA-β-Gal) kit. Mitophagy was determined through transmission electron microscopy, TMRM staining, and Western blotting analysis of p62. A model of aging blood vessels was induced by D-gal. The vascular wall thickness of mice was also evaluated by H&E staining. Our data proved that AS-IV plays an anti-senescent role in vitro and in vivo. Results showed that AS-IV effectively improved mitochondrial injury, raised MMP, and mediated mitophagy in BLM-induced senescent VSMCs and D-gal induced aging mice. Parkin expression strengthened AS-IV's anti-senescent function. In conclusions, AS-IV attenuated BLM-induced VSMC senescence via Parkin to regulate mitophagy. Therefore, AS-IV-mediated Parkin might be a latent therapeutic agent and target for VSMC senescence.