Department of Biology, College of Natural Sciences, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 501759, Korea.
BK21-Plus Research Team for Bioactive Control Technology, Department of Life Science, Chosun University, Gwangju 61452, Korea.
Int J Mol Sci. 2021 Jul 7;22(14):7324. doi: 10.3390/ijms22147324.
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.
氧化应激的增加是细胞衰老和老化进展的关键因素。本研究旨在探讨甘草查尔酮 D（Lico D）在体外和体内对氧化应激诱导的衰老的影响，并探讨其潜在机制。过氧化氢（200µM 作用双时）和 D-半乳糖（D-Gal）（150mg/kg）分别用于诱导人骨髓间充质干细胞（hBM-MSCs）和小鼠的氧化应激。我们进行了 SA-β-半乳糖苷酶测定，并评估了衰老标志物、AMPK 的激活和自噬。Lico D 通过上调 AMPK 介导的自噬，可能减轻 hBM-MSCs 中氧化应激诱导的衰老。D-Gal 处理显著增加了心脏和海马组织中衰老标志物（如 p53 和 p21）的表达水平，而 Lico D 处理的动物则逆转了这种效应。此外，在这两个组织中均观察到 AMPK 激活显著增加，而自噬的激活仅在心脏组织中观察到。有趣的是，我们发现 Lico D 显著降低了海马组织中晚期糖基化终产物（RAGE）受体的表达水平。综上所述，我们的研究结果强调了 Lico D 的抗氧化、抗衰老和心脏保护作用，并表明 AMPK 和自噬的激活可改善氧化应激诱导的衰老。
