甘草素是甘草中的一种生物活性成分，通过调节铁死亡和 VEGF/Akt/ERK 通路改善糖尿病肾病。

Glabridin, a bioactive component of licorice, ameliorates diabetic nephropathy by regulating ferroptosis and the VEGF/Akt/ERK pathways.

机构信息

Department of Traditional Chinese Medicine, Huizhou Municipal Central Hospital, Huicheng District, No. 41 Eling North Road, Huizhou, 516000, Guangdong, China.

The First College of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Mol Med. 2022 May 20;28(1):58. doi: 10.1186/s10020-022-00481-w.

DOI:10.1186/s10020-022-00481-w

PMID:35596156

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9123664/

Abstract

BACKGROUND

Glabridin (Glab) is a bioactive component of licorice that can ameliorate diabetes, but its role in diabetic nephropathy (DN) has seldom been reported. Herein, we explored the effect and underlying mechanism of Glab on DN.

METHODS

The bioactive component-target network of licorice against DN was by a network pharmacology approach. The protective effect of Glab on the kidney was investigated by a high-fat diet with streptozotocin induced-diabetic rat model. High glucose-induced NRK-52E cells were used for in vitro studies. The effects of Glab on ferroptosis and VEGF/Akt/ERK pathways in DN were investigated in vivo and in vitro using qRT-PCR, WB, and IHC experiments.

RESULTS

Bioinformatics analysis constructed a network comprising of 10 bioactive components of licorice and 40 targets for DN. 13 matching targets of Glab were mainly involved in the VEGF signaling pathway. Glab treatment ameliorated general states and reduced FBG, HOMA-β, and HOMA-insulin index of diabetic rats. The renal pathological changes and the impaired renal function (the increased levels of Scr, BUN, UREA, KIM-1, NGAL, and TIMP-1) were also improved by Glab. Moreover, Glab repressed ferroptosis by increasing SOD and GSH activity, and GPX4, SLC7A11, and SLC3A2 expression, and decreasing MDA and iron concentrations, and TFR1 expression, in vivo and in vitro. Mechanically, Glab significantly suppressed VEGF, p-AKT, p-ERK1/2 expression in both diabetic rats and HG-induced NRK-52E cells.

CONCLUSIONS

This study revealed protective effects of Glab on the kidney of diabetic rats, which might exert by suppressing ferroptosis and the VEGF/Akt/ERK pathway.

摘要

背景

甘草素（Glab）是甘草中的一种生物活性成分，可改善糖尿病，但它在糖尿病肾病（DN）中的作用鲜有报道。本研究旨在探讨 Glab 对 DN 的作用及其机制。

方法

采用网络药理学方法构建甘草治疗 DN 的活性成分-靶标网络。通过高脂饮食联合链脲佐菌素诱导的糖尿病大鼠模型研究 Glab 对肾脏的保护作用。体外实验采用高糖诱导 NRK-52E 细胞。采用 qRT-PCR、WB 和 IHC 实验，在体内和体外研究 Glab 对 DN 中铁死亡和 VEGF/Akt/ERK 通路的影响。

结果

生物信息学分析构建了一个包含 10 种甘草活性成分和 40 个 DN 靶点的网络。Glab 的 13 个匹配靶点主要参与 VEGF 信号通路。Glab 治疗改善了糖尿病大鼠的一般状态，降低了 FBG、HOMA-β 和 HOMA-Insulin 指数。肾脏病理变化和受损的肾功能（Scr、BUN、UREA、KIM-1、NGAL 和 TIMP-1 水平升高）也得到改善。此外，Glab 通过增加 SOD 和 GSH 活性以及 GPX4、SLC7A11 和 SLC3A2 的表达，降低 MDA 和铁浓度以及 TFR1 的表达，在体内和体外抑制铁死亡。机制上，Glab 显著抑制了糖尿病大鼠和 HG 诱导的 NRK-52E 细胞中 VEGF、p-AKT 和 p-ERK1/2 的表达。