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从降香黄檀中分离得到的异帕夫呋喃通过激活 SIRT1 和抑制 AKT/mTOR 通路来减轻 HO 诱导的 BJ 细胞衰老。

Isoparvifuran isolated from Dalbergia odorifera attenuates HO-induced senescence of BJ cells through SIRT1 activation and AKT/mTOR pathway inhibition.

机构信息

Department of Anesthesiology, Affiliated Hospital of Jiujiang University, Jiujiang, 332000, China; Department of Biochemistry, School of Medicine, Wonkwang University, Iksan, 54538, Republic of Korea.

Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2020 Dec 17;533(4):925-931. doi: 10.1016/j.bbrc.2020.09.096. Epub 2020 Sep 30.

DOI:10.1016/j.bbrc.2020.09.096
PMID:33010892
Abstract

Isoparvifuran is a benzofuran compound isolated from the heartwood of Dalbergia odorifera. Related research reported that isoparvifuran has antioxidant property. However, it is unclear whether isoparvifuran has anti-aging effects. In this research, we established an aging model, hydrogen peroxide (HO)-induced BJ cell senescence, to explore the protective effect of isoparvifuran on cell senescence and its related mechanisms. Our results revealed that isoparvifuran obviously attenuated HO-induced cell senescence, increased the cell proliferation rate,and reversed senescence-associated molecular markers expression such as cyclin D1, pRb, caveolin-1, ace-p53, p21 and p16. Moreover, isoparvifuran dose and time dependently increased the expression level of Sirtuin 1 (SIRT1) in BJ cells. The inhibition of SIRT1 obviously reversed the reduction of SA-β-gal activity and the alteration of senescence-associated molecular markers induced by isoparvifuran. Additionally, isoparvifuran also inhibited HO-induced AKT and S6 phosphorylation and increase of SA-β-gal activity. In summary, isoparvifuran protects BJ cells from HO-induced premature senescence, the anti-senescence effect of isoparvifuran is associated with the activation of SIRT1 and the suppression of AKT/mTOR signaling pathway.

摘要

异戊呋喃是从降香黄檀心材中分离得到的苯并呋喃化合物。相关研究报道,异戊呋喃具有抗氧化活性。然而,其是否具有抗衰老作用尚不清楚。在这项研究中,我们建立了衰老模型,即过氧化氢(HO)诱导的 BJ 细胞衰老,以探讨异戊呋喃对细胞衰老的保护作用及其相关机制。研究结果表明,异戊呋喃明显减轻了 HO 诱导的细胞衰老,提高了细胞增殖率,并逆转了衰老相关分子标志物的表达,如细胞周期蛋白 D1、pRb、窖蛋白-1、ace-p53、p21 和 p16。此外,异戊呋喃呈剂量和时间依赖性地增加了 BJ 细胞中 Sirtuin 1(SIRT1)的表达水平。SIRT1 的抑制明显逆转了异戊呋喃诱导的 SA-β-半乳糖苷酶活性降低和衰老相关分子标志物的改变。此外,异戊呋喃还抑制了 HO 诱导的 AKT 和 S6 磷酸化以及 SA-β-半乳糖苷酶活性的增加。综上所述,异戊呋喃可保护 BJ 细胞免受 HO 诱导的过早衰老,异戊呋喃的抗衰老作用与 SIRT1 的激活以及 AKT/mTOR 信号通路的抑制有关。

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