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, respectively. 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 upregulating 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 hippocampal tissues, while this effect was reversed in the Lico D-treated animals. Furthermore, a significant 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.

Camphorquinone Promotes the Antisenescence Effect via Activating AMPK/SIRT1 in Stem Cells and D-Galactose-Induced Aging Mice

“…Human bone marrow mesenchymal stem cells (hBM-MSCs) were purchased and cultured as described previously [ 11 ]. The cells were continuously monitored under a bright field microscope (Nikon Eclipse TS100; Tokyo, Japan) and subcultured as soon as confluence was reached.…”

“…H 2 O 2 was used to instigate oxidative-stress-induced cell cycle arrest and senescence, as described previously [ 11 ]. Briefly, the cells were exposed to 200 µM H 2 O 2 for 2 h and cultured for 2 days in normal media.…”

“…Senescence-associated β-galactosidase-positive cells were identified using an SA-β-gal assay kit, as described previously [ 11 ]. Briefly, after 72 h of treatment with compounds, cells were washed with phosphate-buffered saline (1X PBS) (Takara Bio Inc., Shiga, Japan) and fixed with 1X fixative for 10–15 min at room temperature.…”

“…A variety of senescence models, including the oxidative-stress-induced senescence model, have been adopted to better understand the molecular mechanisms underlying senescence. Oxidative stress is a type of stress-induced premature senescence (SIPS) that can be utilized to investigate the mechanism of cellular senescence both in vitro and in vivo [ 8 , 9 , 10 , 11 ]. Activation of AMPK, SIRT1, and autophagy mechanisms has been shown to prevent oxidative-stress-induced senescence [ 11 , 12 , 13 ].…”

“…Oxidative stress is a type of stress-induced premature senescence (SIPS) that can be utilized to investigate the mechanism of cellular senescence both in vitro and in vivo [ 8 , 9 , 10 , 11 ]. Activation of AMPK, SIRT1, and autophagy mechanisms has been shown to prevent oxidative-stress-induced senescence [ 11 , 12 , 13 ]. To alleviate oxidative-stress-induced senescence and aging, a novel medication or compound that can activate AMPK, SIRT1, and autophagy is required.…”