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.
Biomed Pharmacother. 2021 Jun;138:111305. doi: 10.1016/j.biopha.2021.111305. Epub 2021 Apr 2.
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.
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.
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.
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.
In conclusion, rehmapicrogenin attenuates kidney damage by reducing inflammatory factor release through the oestrogen signalling pathway.
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。
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。
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。
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。
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。