Shenqi Dihuang Decoction inhibits high-glucose induced ferroptosis of renal tubular epithelial cells via Nrf2/HO-1/GPX4 pathway.
10.19540/j.cnki.cjcmm.20230721.501
- Author:
Zhi-Bin WANG
1
;
Xiao-Ling ZOU
2
;
Yi-Xian ZOU
2
;
Li-Huai WANG
2
;
Yuan-Tao WU
2
Author Information
1. Department of Endocrinology, the First Hospital of Hunan University of Chinese Medicine Changsha 410007, China Graduate School, Hunan University of Chinese Medicine Changsha 410208, China.
2. Department of Endocrinology, the First Hospital of Hunan University of Chinese Medicine Changsha 410007, China.
- Publication Type:Journal Article
- Keywords:
Nrf2/HO-1/GPX4 pathway;
Shenqi Dihuang Decoction;
diabetic kidney disease;
ferroptosis
- MeSH:
Humans;
Ferroptosis;
NF-E2-Related Factor 2/genetics*;
Reactive Oxygen Species;
Epithelial Cells;
Antioxidants;
Glutathione;
Glucose
- From:
China Journal of Chinese Materia Medica
2023;48(19):5337-5344
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to explore the effects of Shenqi Dihuang Decoction on high-glucose induced ferroptosis and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) axis in human renal tubular epithelial cells(HK-2) and to clarify the underlying mechanism. The cell injury model was established by exposing HK-2 to high glucose, and the Shenqi Dihuang Decoction-medicated serum was prepared. The optimal concentration and intervention time of Shenqi Dihuang Decoction were determined. HK-2 were divided into normal, high glucose, and low-, medium-, and high-dose Shenqi Dihuang Decoction groups. After interventions, the cell proliferation rate in each group was determined and the cell morphology and mitochondrial ultrastructure were observed. Then, the levels of intracellular reactive oxygen species(ROS), ferrous ion(Fe~(2+)), glutathione(GSH), and malondialdehyde(MDA) and the protein levels of Nrf2, HO-1, GPX4, and xCT were measured. The optimal concentration and intervention time of Shenqi Dihuang Decoction-medicated serum were determined to be 10% and 24 h, respectively. Compared with the high glucose group, high-dose Shenqi Dihuang Decoction promoted the proliferation of HK-2. The cells in the low-, medium-, and high-dose Shenqi Dihuang Decoction groups presented tight arrangement, an increased cell count, improved morphology from a spindle-fiber shape to a cobblestone shape, and improved morphology and structure of mitochondrial membrane and cristae, compared with those in the high glucose group. Meanwhile, all the doses of Shenqi Dihuang Decoction inhibited ROS elevation to mitigate the peroxidation damage, lowered the Fe~(2+) and MDA levels and elevated the GSH level to inhibit lipid peroxidation, and activated the antioxidant pathway to upregulate the protein levels of Nrf2, HO-1, xCT, and GPX4. In conclusion, Shenqi Dihuang Decoction-medicated serum can inhibit high-glucose induced ferroptosis of HK-2 in vitro, which involves the antioxidant effect and the activation of the Nrf2/HO-1/GPX4 pathway.
