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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Renal Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1508312

Curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4

Provisionally accepted
Mengjiao Xue Mengjiao Xue 1Yiwei Tian Yiwei Tian 2Hua Zhang Hua Zhang 1Shijie Dai Shijie Dai 3Yang-Sheng Wu Yang-Sheng Wu 3Juan Jin Juan Jin 4*Jian Chen Jian Chen 2*
  • 1 Hangzhou Medical College, Hangzhou, Zhejiang Province, China
  • 2 Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
  • 3 Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
  • 4 First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    The aim of this study was to investigate the effect of curcumin nanocrystals (Cur-NCs) on ferroptosis in high-glucose (HG)-induced HK-2 cells and streptozotocin (STZ)-induced diabetic nephropathy model (DN) rats. The purpose is to determine whether Cur NCs can become a promising treatment option for diabetes nephropathy by reducing ferroptosis.Methods: Cur-NCs were prepared using microfluidic technology and studied using dynamic light scattering and transmission electron microscopy. HK-2 cells were treated with 30 mM HG to create a renal tubule damage cell model. Then, cell viability was evaluated in HK-2 cells treated with varying concentrations of Cur-NCs (0.23, 0.47, 0.94, 1.87, 3.75, 7.5, 15, and 30 μg/mL) using Cell Counting Kit-8 (CCK-8). Furthermore, in vivo experiments were carried out to investigate the roles of Cur-NCs in STZ-induced DN rats.The results showed that HG treatment greatly enhanced the levels of LDH, MDA, Iron, lipid ROS, apoptosis, NCOA4, TFR-1, while decreasing the expression of GSH, GPX4, SLC7A11, and FTH-1. These effects induced by HG could be attenuated by Cur-NCs. Cur-NCs also reduced the HG-induced decrease in cell viability, as well as the increase in lipid ROS and cell apoptosis, however erastin could inhibit their effects. Furthermore, the in vivo results showed that Cur-NCs reduced ferroptosis and inhibited renal damage in DN rats.This study demonstrates that Cur-NCs can significantly attenuate ferroptosis in a STZ-induced renal damage model by recovering GPX4, implying that Cur-NCs may be a promising therapy option for DN.

    Keywords: Curcumin, nanocrystals, ferroptosis, diabetic nephropathy, GPx4

    Received: 09 Oct 2024; Accepted: 05 Dec 2024.

    Copyright: © 2024 Xue, Tian, Zhang, Dai, Wu, Jin and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Juan Jin, First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310003, Zhejiang Province, China
    Jian Chen, Shanghai Jiao Tong University, Shanghai, 200240, Shanghai Municipality, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.