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

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The nephroprotective effects and mechanisms of rehmapicrogenin include ROS inhibition via an oestrogen-like pathway both in vivo and in vitro
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2021-04-02 , DOI: 10.1016/j.biopha.2021.111305
Mengmeng Wang ₁ , Yingying Ke ₁ , Yage Li ₁ , Zengfu Shan ₁ , Wangyang Mi ₁ , Yangang Cao ₁ , Weisheng Feng ₂ , Xiaoke Zheng ₂

Affiliation

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.

中文翻译：

Rehmapicrogenin的肾脏保护作用和机制包括体内和体外通过雌激素样途径抑制ROS

背景

熟地黄（R. glutinosa）的根通常用于各种传统中草药配方中以改善肾病。然而，对其活性成分和机制知之甚少。

目的

在本研究中，我们检查了保护作用和rehmapicrogenin，从提取的单体化合物的潜在机制地黄，对阿霉素（ADR）诱导的肾病（AN）在体内和体外。

方法

在这项研究中，采用ADR诱导的肾脏损伤模型来研究rehmapicrogenin对小鼠的肾脏保护作用。在体内，使用ELISA试剂盒，流式细胞仪，苏木精-伊红染色，免疫荧光技术和Western印迹法来评估rehmapicrogenin对小鼠肾脏损伤的作用。在体外，使用3-（4,5-二甲基噻唑基-2-基）-2,5-二苯基四唑溴化物（MTT）方法测定了瑞克帕克罗丁菌素对ADR诱导的NRK-52E细胞损伤的影响。使用ELISA试剂盒，流式细胞仪和In-Cell Western™印迹对机理进行了研究。

结果

在体内，Rehmapicrogenin治疗可显着减轻ADR所致肾脏的病理变化。挽救体重，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；降低了ADR处理的小鼠的氧化应激，凋亡率和细胞存活率。重要的是，在体内和体外实验结果表明，rehmapicrogenin调节Nrf2 / ARE信号传导途径，这是氧化应激最重要的途径。Rehmapicrogenin通过减少通过雌激素受体途径的氧化应激而减轻了ADR诱导的肾脏损害。此外，在用ICI 182780（雌激素受体非特异性拮抗剂Faslodex）治疗后，rehmapicrogenin引起的改善显着逆转。