Radioprotection by quercetin-3-O-rutinoside, a flavonoid glycoside - A cellular and mechanistic approach

Radioprotection by quercetin-3-O-rutinoside, a flavonoid glycoside - A cellular and mechanistic approach
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DOI:
10.1016/j.jff.2012.06.010
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发表时间:
2012-10-01
影响因子:
5.6
通讯作者:
Unnikrishnan, M. K.
Unnikrishnan, M. K.
中科院分区:
农林科学2区
文献类型:
--
作者:
Bansal, Punit;Paul, Piya;Unnikrishnan, M. K.

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研究小叶冷水花中黄酮苷类化合物槲皮素-3-O-尼替诺苷(PMC-1)的体内辐射防护作用。体内存活研究确定了PMC-1的最佳有效剂量为25 mg/kg/i. p.。在最佳剂量下,PMC-1可防止辐照小鼠肝脏中内源性抗氧化剂的耗竭。通过恢复辐射诱导的绒毛高度、隐窝细胞数量和脾指数的降低证实了对胃肠道和造血系统的体内保护。PMC-1对辐射诱导的脾细胞凋亡也有明显的抑制作用。外周血白细胞的单细胞凝胶电泳显示PMC-1抑制辐射诱导的DNA损伤。与辐射对照相比,PMC-1预处理通过增加促存活(ERK)和降低促凋亡(BAX)基因表达显著逆转了这些变化。因此,PMC-1表现出对γ-辐射的保护作用,其可能的作用机制包括维持抗氧化酶、预防作用和抑制细胞凋亡。(C)2012爱思唯尔有限公司保留所有权利。
The present study was aimed to evaluate the in vivo radioprotective efficacy of quercetin-3-O-nitinoside (PMC-1), the key bioactive constituent flavonoid glycoside isolated from the whole plant of Pilea microphylla was evaluated. In vivo survival studies established the optimum effective dose of PMC-1 at 25 mg/kg/i.p. At the optimum dose, PMC-1 prevented the depletion of endogenous antioxidants in the liver of irradiated mice. In vivo protection towards gastrointestinal tract and haematopoietic system was confirmed by the restoration of radiation-induced reduction in villi height, number of crypt cells and spleen index. PMC-1 also attenuated the radiation-induced apoptosis in spleenocytes significantly. Single cell gel electrophoresis of peripheral blood leukocytes showed inhibition of radiation-induced DNA damage by PMC-1. PMC-1 pretreatment significantly reversed the changes by increasing pro-survival (ERK) and decreasing pro-apoptotic (BAX) gene expressions compared to radiation control. Thus, PMC-1 exhibits protective effects against gamma-radiation and the probable mechanism of action involves maintenance of antioxidant enzymes, prophylactic action and inhibition of apoptosis. (C) 2012 Elsevier Ltd. All rights reserved.