Curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4

ObjectiveThe 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 o...

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Main Authors: Mengjiao Xue, Yiwei Tian, Hua Zhang, Shijie Dai, Yangsheng Wu, Juan Jin, Jian Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1508312/full
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author Mengjiao Xue
Mengjiao Xue
Yiwei Tian
Hua Zhang
Hua Zhang
Shijie Dai
Yangsheng Wu
Juan Jin
Juan Jin
Jian Chen
author_facet Mengjiao Xue
Mengjiao Xue
Yiwei Tian
Hua Zhang
Hua Zhang
Shijie Dai
Yangsheng Wu
Juan Jin
Juan Jin
Jian Chen
author_sort Mengjiao Xue
collection DOAJ
description ObjectiveThe 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.MethodsCur-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.ResultsThe 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.ConclusionThis 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.
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publishDate 2025-01-01
publisher Frontiers Media S.A.
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spelling doaj-art-804b2010b05240918e59a47ea2d9cba92025-01-06T06:59:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15083121508312Curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4Mengjiao Xue0Mengjiao Xue1Yiwei Tian2Hua Zhang3Hua Zhang4Shijie Dai5Yangsheng Wu6Juan Jin7Juan Jin8Jian Chen9School of Clinical Medicine, Hangzhou Medical College, Hangzhou, ChinaDepartment of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaSchool of Pharmacy, Shanghai Jiaotong University, Shanghai, ChinaSchool of Clinical Medicine, Hangzhou Medical College, Hangzhou, ChinaDepartment of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaCollege of Life Science, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Life Science, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Clinical Medicine, Hangzhou Medical College, Hangzhou, ChinaDepartment of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaSchool of Pharmacy, Shanghai Jiaotong University, Shanghai, ChinaObjectiveThe 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.MethodsCur-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.ResultsThe 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.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fphar.2024.1508312/fullcurcuminnanocrystalsferroptosisdiabetic nephropathyGPX4
spellingShingle Mengjiao Xue
Mengjiao Xue
Yiwei Tian
Hua Zhang
Hua Zhang
Shijie Dai
Yangsheng Wu
Juan Jin
Juan Jin
Jian Chen
Curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4
Frontiers in Pharmacology
curcumin
nanocrystals
ferroptosis
diabetic nephropathy
GPX4
title Curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4
title_full Curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4
title_fullStr Curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4
title_full_unstemmed Curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4
title_short Curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4
title_sort curcumin nanocrystals ameliorate ferroptosis of diabetic nephropathy through glutathione peroxidase 4
topic curcumin
nanocrystals
ferroptosis
diabetic nephropathy
GPX4
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1508312/full
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