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瑞马新碱的肾保护作用及其机制包括在体内和体外通过类雌激素途径抑制 ROS。

The nephroprotective effects and mechanisms of rehmapicrogenin include ROS inhibition via an oestrogen-like pathway both in vivo and in vitro.

机构信息

Henan University of Chinese Medicine, Zhengzhou 450046, China.

Henan University of Chinese Medicine, Zhengzhou 450046, China; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou 450046, China.

出版信息

Biomed Pharmacother. 2021 Jun;138:111305. doi: 10.1016/j.biopha.2021.111305. Epub 2021 Apr 2.

Abstract

BACKGROUND

The root of Rehmannia glutinosa (R. glutinosa) is commonly used in various traditional Chinese herbal formulae to ameliorate nephropathy; however, little is known about its active component(s) and mechanisms.

AIM

In the present study, we examined the protective effect and potential mechanism of rehmapicrogenin, a monomeric compound extracted from R. glutinosa, against Adriamycin (ADR)-induced nephropathy (AN) in vivo and in vitro.

METHODS

In this study, an ADR-induced kidney injury model was employed to investigate the nephroprotective effects of rehmapicrogenin in mice. In vivo, ELISA kits, flow cytometry, haematoxylin-eosin staining, immunofluorescence techniques, and western blotting were used to evaluate the effect of rehmapicrogenin on kidney injury in mice. In vitro, the effects of rehmapicrogenin on NRK-52E cellular damage induced by ADR were determined using the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The mechanism was investigated using ELISA kits, flow cytometry and In-Cell Western™ blotting.

RESULTS

In vivo, rehmapicrogenin treatment significantly attenuated the pathological changes in the kidney induced by ADR; rescued weight, serum creatinine (Scr), blood urea nitrogen (BUN) and urine albumin (U-ALB) levels; reduced reactive oxygen species (ROS) accumulation; and decreased oxidative stress, the apoptosis rate, and cell survival in ADR-treated mice. Importantly, both in vivo and in vitro experimental results demonstrated that rehmapicrogenin regulates the Nrf2/ARE signalling pathway, the most important pathway for oxidative stress. Rehmapicrogenin attenuated ADR-induced kidney damage by reducing oxidative stress through the oestrogen receptor pathway. Moreover, after treatment with ICI 182780 (the oestrogen receptor-nonspecific antagonist Faslodex), the improvement induced by rehmapicrogenin was significantly reversed.

CONCLUSIONS

In conclusion, rehmapicrogenin attenuates kidney damage by reducing inflammatory factor release through the oestrogen signalling pathway.

摘要

背景

地黄的根通常用于各种中药方剂中以改善肾病;然而,其活性成分和机制知之甚少。

目的

本研究旨在探讨从地黄中提取的单体化合物梓醇苷对阿霉素(ADR)诱导的体内和体外肾病(AN)的保护作用及其潜在机制。

方法

在这项研究中,我们使用 ADR 诱导的肾损伤模型来研究梓醇苷对小鼠的肾保护作用。体内,采用 ELISA 试剂盒、流式细胞术、苏木精-伊红染色、免疫荧光技术和 Western blot 来评估梓醇苷对小鼠肾损伤的影响。体外,采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法测定梓醇苷对 ADR 诱导的 NRK-52E 细胞损伤的影响。采用 ELISA 试剂盒、流式细胞术和 In-Cell Western™ 印迹法研究其作用机制。

结果

体内,梓醇苷治疗可显著减轻 ADR 引起的肾脏病理变化;恢复体重、血清肌酐(Scr)、血尿素氮(BUN)和尿白蛋白(U-ALB)水平;减少活性氧(ROS)积累;降低 ADR 处理小鼠的氧化应激、细胞凋亡率和细胞存活率。重要的是,体内和体外实验结果均表明,梓醇苷通过调节氧化应激最重要的途径 Nrf2/ARE 信号通路来调节氧化应激。梓醇苷通过雌激素受体途径减轻 ADR 引起的肾脏损伤,从而减少氧化应激。此外,用 ICI 182780(雌激素受体非特异性拮抗剂 Faslodex)处理后,梓醇苷的改善作用明显逆转。

结论

总之,梓醇苷通过雌激素信号通路减少炎症因子的释放来减轻肾脏损伤。

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