Research Paper Volume 15, Issue 15 pp 7673—7688
Emodin attenuates diabetic kidney disease by inhibiting ferroptosis via upregulating Nrf2 expression
- 1 Department of Emergency, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
- 2 Department of Nephrology Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
- 3 Department of Central Laboratory, Postdoctoral Workstation, The Affiliated Taian City Central Hospital of Qingdao University, Taian 271000, China
- 4 Department of Rehabilitation, The Second Affiliated Hospital of Shandong First Medical University, Taian 271000, China
- 5 Department of Endocrinology, The Second Affiliated Hospital of Shandong First Medical University, Taian 271000, China
Received: March 8, 2023 Accepted: July 15, 2023 Published: August 7, 2023
https://doi.org/10.18632/aging.204933How to Cite
Copyright: © 2023 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Diabetic kidney disease (DKD) poses a threat to people’s health. The current treatments only provide partial relief of symptoms. Therefore, seeking a promising therapeutic medication for the prevention and control on DKD will benefit patients. Recently, a novel iron-dependent and non-apoptotic regulated mode of cell death, termed as ferroptosis, is expected to offer us a novel insight into the mechanism of DKD. We conducted experiments to investigate the role of ferroptosis in the development of DKD. Iron accumulation, weakened antioxidant capacity and ROS overproduction were observed in the renal tissues of STZ-induced diabetic rats. A persistent high glucose condition contributed to down regulated levels of Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11) which marked the occurrence of ferroptosis. Treatment of Emodin in DKD models could significantly attenuated these changes and reduced renal injury. Besides, NFE2-related factor 2 (Nrf2), an important antioxidant regulator, was inhibited in both in vivo and in vitro assay, which contributes to Reactive Oxygen Species (ROS) generation that further promoted the expression of ferroptosis related protein. These unwanted effects were offset by the intervention of Emodin. The specific Nrf2 knock out enhanced cell’s sensitivity to ferroptosis by being exposed to high glucose culture, which was improved by treatment of Emodin via restoring activity of Nrf2. In conclusion, our research demonstrated that Emodin exerted renal protection against DKD via inhibiting ferroptosis and restoring Nrf2 mediated antioxidant capacity, which could be employed as a novel therapeutic medication against DKD.