Lim Seok-Hee, Li Bing Si, Zhu Ri Zhe, Seo Jae-Ho, Choi Byung-Min
Department of Biochemistry, Wonkwang University School of Medicine.
Biol Pharm Bull. 2020 Jul 1;43(7):1104-1110. doi: 10.1248/bpb.b20-00094. Epub 2020 May 12.
Latifolin, a natural flavonoid found in Dalbergia odorifera T. Chen, has been reported to exhibit anti-inflammatory and anticarcinogenic activities in vitro. However, the anti-aging effects of latifolin are unknown. In this study, we selected a model in vitro system, hydrogen peroxide (HO)-induced senescence in human dermal fibroblasts (HDFs), to examine the protective effects of latifolin against senescence and the detailed molecular mechanisms involved. Latifolin reversed the senescence-like phenotypes of the oxidant-challenged model, including senescence-associated β-galactosidase (SA-β-gal) staining, cell proliferation, and the expression of senescence-related proteins, such as caveolin-1, ac-p53, p21, p16, pRb, and cyclinD1. We also found that latifolin induced the expression of silent information regulator 1 (SIRT1) in a concentration- and time-dependent manner, and the anti-senescence effect of latifolin was abrogated by SIRT1 inhibition. Latifolin also suppressed the activation of Akt and S6K1 and attenuated the increase in SA-β-gal activity after HO exposure. Our results indicate that latifolin exerts protective effects against senescence in HDFs and that induction of SIRT1 and inhibition of the mammalian target of rapamycin (mTOR) pathway are key mediators of its anti-aging effects.
降香黄酮是在降香檀中发现的一种天然黄酮类化合物，据报道其在体外具有抗炎和抗癌活性。然而，降香黄酮的抗衰老作用尚不清楚。在本研究中，我们选择了一种体外模型系统，即过氧化氢（H₂O₂）诱导的人皮肤成纤维细胞（HDFs）衰老，以研究降香黄酮对衰老的保护作用及其相关的详细分子机制。降香黄酮逆转了氧化应激模型的衰老样表型，包括衰老相关β-半乳糖苷酶（SA-β-gal）染色、细胞增殖以及衰老相关蛋白如小窝蛋白-1、乙酰化p53、p21、p16、磷酸化视网膜母细胞瘤蛋白（pRb）和细胞周期蛋白D1的表达。我们还发现，降香黄酮以浓度和时间依赖性方式诱导沉默信息调节因子1（SIRT1）的表达，并且SIRT1抑制可消除降香黄酮的抗衰老作用。降香黄酮还抑制了Akt和S6K1的激活，并减弱了H₂O₂暴露后SA-β-gal活性的增加。我们的结果表明，降香黄酮对HDFs的衰老具有保护作用，并且诱导SIRT1和抑制雷帕霉素靶蛋白（mTOR）途径是其抗衰老作用的关键介质。
