Investigation of quercetin and hyperoside as senolytics in adult human endothelial cells.
Investigation of quercetin and hyperoside as senolytics in adult human endothelial cells.
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DOI：
10.1371/journal.pone.0190374
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Knowlton AA
中科院分区：
文献类型：
--
作者：
Hwang HV;Tran DT;Rebuffatti MN;Li CS;Knowlton AA
据报道，槲皮素通过选择性地去除衰老的内皮细胞而起到了抗衰老作用，因此，它似乎可以彻底改变老年学领域。然而，考虑到在对人脐静脉内皮细胞(HUVECs)进行的研究中报道的槲皮素的狭窄治疗指数，我们假设，在已报道的对HUVECs增殖安全的浓度下，槲皮素对非衰老的成人血管内皮细胞并不是无害的。此外，我们还研究了一种在衰老细胞中过度表达的β-半乳糖苷酶需要裂解的失活的栎素衍生物--3-D-半乳糖苷(Q3G；金丝桃苷)，作为潜在的更安全的感觉剂。我们比较了Quercetin和Q3G在原代培养的人冠状动脉内皮细胞(HCAEC)中的效果，HCAEC是成人微血管细胞。我们发现，在已报道的选择性清除衰老细胞的浓度下，Q3G会导致非衰老内皮细胞的细胞死亡，而且Q3G对年轻细胞和衰老细胞都没有细胞毒性。因此，在原代成人内皮细胞中，Quercetin和Q3G不是感觉剂。早期报道阳性结果的工作是用HUVEC进行的，考虑到它们的来源和当前研究的不同发现，这些细胞可能不是评估临床相关内皮细胞潜在感觉神经降解剂的最佳细胞。此前，有报道称，在HUVECs中，槲皮素是一种有选择性地去除衰老细胞的抗衰老药物。然而，我们发现，槲皮素和Q3G对成人内皮细胞都不是有效的感觉剂。
Quercetin has been reported to act as a senolytic by selectively removing senescent endothelial cells, and thus it would seem quercetin could revolutionize the field of gerontology. However, given quercetin's narrow therapeutic index reported in work done with human umbilical vein endothelial cells (HUVECs), we hypothesized that quercetin is not innocuous for non-senescent adult human vascular endothelial cells at concentrations that have been reported to be safe for proliferating HUVECs. Furthermore, we investigated quercetin 3-D-galactoside (Q3G; hyperoside), an inactive quercetin derivative that needs to be cleaved by beta-galactosidase overexpressed in senescent cells to release quercetin, as a potential safer senolytic. We compared the effectiveness of quercetin and Q3G in primary human coronary artery endothelial cells (HCAEC), which are adult microvascular cells. We found that quercetin caused cell death in non-senescent endothelial cells at a concentration that has been reported to selectively remove senescent cells, and that Q3G was not cytotoxic to either young or senescent cells. Thus, in primary adult human endothelial cells, quercetin and Q3G are not senolytics. Earlier work reporting positive results was done with HUVECs, and given their origin and the disparate findings from the current study, these may not be the best cells for evaluating potential senolytics in clinically relevant endothelial cells. Previously, quercetin has been reported to be a senolytic, a drug that selectively removes senescent cells, in HUVECs. However, we found neither quercetin nor Q3G was effective as a senolytic for adult human endothelial cells.
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影响因子：
16.6
作者：
Fuhrmann-Stroissnigg H;Ling YY;Zhao J;McGowan SJ;Zhu Y;Brooks RW;Grassi D;Gregg SQ;Stripay JL;Dorronsoro A;Corbo L;Tang P;Bukata C;Ring N;Giacca M;Li X;Tchkonia T;Kirkland JL;Niedernhofer LJ;Robbins PD
通讯作者：
Robbins PD
影响因子：
3.3
作者：
Freund A;Laberge RM;Demaria M;Campisi J
通讯作者：
Campisi J
影响因子：
2.6
作者：
Bernatoniene, Jurga;Masteikova, Ruta;Peciura, Rimantas
通讯作者：
Peciura, Rimantas
影响因子：
64.5
作者：
Dai, Chengkai;Whitesell, Luke;Lindquist, Susan
通讯作者：
Lindquist, Susan
影响因子：
4.6
作者：
Kim, HR;Kang, HS;Kim, HD
通讯作者：
Kim, HD