Licochalcone d ameliorates oxidative stress‐induced senescence via ampk activation

Abstract

Increased oxidative stress is a crucial factor for the progression of cellular senescence and aging. The present study aimed to investigate the effects of licochalcone D (Lico D) on oxidative stress‐induced senescence, both in vitro and in vivo, and explore its potential mechanisms. Hydrogen peroxide (200 μM for double time) and D‐galactose (D‐Gal) (150 mg/kg) were used to induce oxidative stress in human bone marrow‐mesenchymal stem cells (hBM‐MSCs) and mice, respec-tively. We performed the SA‐β‐gal assay and evaluated the senescence markers, activation of AMPK, and autophagy. Lico D potentially reduced oxidative stress‐induced senescence by upreg-ulating AMPK‐mediated activation of autophagy in hBM‐MSCs. D‐Gal treatment significantly increased the expression levels of senescence markers, such as p53 and p21, in the heart and hippo-campal tissues, while this effect was reversed in the Lico D‐treated animals. Furthermore, a signifi-cant increase in AMPK activation was observed in both tissues, while the activation of autophagy was only observed in the heart tissue. Interestingly, we found that Lico D significantly reduced the expression levels of the receptors for advanced glycation end products (RAGE) in the hippocampal tissue. Taken together, our findings highlight the antioxidant, anti‐senescent, and cardioprotective effects of Lico D and suggest that the activation of AMPK and autophagy ameliorates the oxidative stress‐induced senescence.