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.

Suppression of NLRP3 inflammasome activation by astragaloside IV via promotion of mitophagy to ameliorate radiation-induced renal injury in mice

“…Furthermore, CsA significantly inhibited the expression of mitophagy markers (PINK1, parkin, and LC3) and aggravated the damage of renal function induced by IR, thereby suggesting the role of mitophagy in the recovery process. In addition, AS-IV was shown to play a protective role by promoting mitophagy, which reduced the accumulation of damaged mitochondria in a vascular senescence model ( 42 ). Our results confirmed that AS-IV administration reduced ROS production, enhanced mitophagy, and attenuated the renal functional deficits and histopathological changes induced by IR.…”

Mitochondrial Homeostasis in VSMCs as a Central Hub in Vascular Remodeling

“…Senescent VSMCs are abundant in atherosclerosis plaques and the vascular wall of the artery disease model [ 42 , 61 ]. Defective mitophagy leads to the accumulation of impaired mitochondria, which is the primary source of mtROS and ultimately contributes to the senescence of VSMCs [ 62 ]. P53 can bind to PINK and prevent its transport to mitochondria, which leads to impaired mitophagy mediated by PINK/Parkin [ 63 ].…”

“…P53 can bind to PINK and prevent its transport to mitochondria, which leads to impaired mitophagy mediated by PINK/Parkin [ 63 ]. It has been shown that activation of PINK/Parkin-mediated mitophagy can alleviate the senescence of VSMCs [ 62 ]. In addition to PINK, an AMPK/SIRT1 signal protects mitophagy by improving bioenergy efficiency [ 63 ].…”

“…This causes mitophagy defects and promotes the senescence of VSMCs [ 63 ]. Astragaloside IV has been proven to alleviate the senescence of VSMCs through activating Parkin-mediated mitophagy, which protects vessels from the lesion ( Table 1 ) [ 62 ]. Therefore, targeting PINK/Parkin-mediated mitophagy is a feasible method to rescue senescence in VSMC.…”

Targeting mitochondrial quality control in muscle aging: Natural dietary products as potential interventions

“…(2018) found that a 30‐day or lifetime dietary intervention with ursolic acid improved the lifespan and climbing ability of Drosophila , the effect that required the stl gene ( Drosophila homolog of PGC‐1α). Astragaloside IV, present in Astragalus membranaceus , reduced inflammatory cell infiltration and β ‐galactosidase levels in the vascular smooth muscle of d ‐galactose‐induced aged mice when intervened at doses of 20/40/80 mg/kg/d (Li et al., 2022). Further, mechanistic investigation through cellular models revealed that the antiaging effect of astragaloside IV on vascular smooth muscle was dependent on Parkin‐mediated mitophagy activation.…”