Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2

Abstract Acute kidney injury (AKI) has become a disease of global concern due to its high morbidity and mortality. This has highlighted the need for renoprotective agents. Astragaloside IV (AS-IV) is a saponin isolated from Astragalus membranaceus with good antioxidant, anti-inflammatory and anti-tu...

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Main Authors: Yuchen Li, Jiayi Zhou, Tianxin Zhang, Xiaocong Li, Cheng Wu, Ziyi Zhao, Jianyuan Tang, Xiaoyu Tan, Qiongying Hu, Wenhao Liao
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86312-4
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author Yuchen Li
Jiayi Zhou
Tianxin Zhang
Xiaocong Li
Cheng Wu
Ziyi Zhao
Jianyuan Tang
Xiaoyu Tan
Qiongying Hu
Wenhao Liao
author_facet Yuchen Li
Jiayi Zhou
Tianxin Zhang
Xiaocong Li
Cheng Wu
Ziyi Zhao
Jianyuan Tang
Xiaoyu Tan
Qiongying Hu
Wenhao Liao
author_sort Yuchen Li
collection DOAJ
description Abstract Acute kidney injury (AKI) has become a disease of global concern due to its high morbidity and mortality. This has highlighted the need for renoprotective agents. Astragaloside IV (AS-IV) is a saponin isolated from Astragalus membranaceus with good antioxidant, anti-inflammatory and anti-tumor properties. In this study, HK2 cells and rat model were utilized to explore the protective effect of AS-IV against cadmium chloride-induced oxidative stress-induced apoptosis. CdCl2-induced apoptosis, ROS production, and mitochondrial membrane potential alterations were significantly inhibited in AS-IV -treated HK2 cells. Expression of the mitochondria-associated apoptotic proteins Cleaved-Caspase3, Cleaved-Caspase9, and Cleaved-PARP was significantly reduced after AS-IV intervention. In addition, AS-IV inhibited Rat weight loss and also alleviated the symptoms of CdCl2-induced nephrotoxicity in a rat model of CdCl2-induced kidney injury. Further experiments showed that AS-IV suppresses heavy metal Cd-induced mitochondria-mediated apoptosis by regulating the Nrf2/HO-1 pathway. In conclusion, AS-IV could protect the kidney from heavy metal-induced toxicity and could be used as a nephroprotective agent.
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spelling doaj-art-974c18e122ff4fe3b15c2ba96ad5d7e62025-01-19T12:19:41ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-025-86312-4Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2Yuchen Li0Jiayi Zhou1Tianxin Zhang2Xiaocong Li3Cheng Wu4Ziyi Zhao5Jianyuan Tang6Xiaoyu Tan7Qiongying Hu8Wenhao Liao9Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese medicineSchool of Medicine, University of Electronic Science and Technology of ChinaDepartment of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese medicineDepartment of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese medicineDepartment of Pathology, Hospital of Chengdu University of Traditional Chinese MedicineTraditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan ProvinceTraditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan ProvinceDepartment of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese medicineDepartment of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese medicineDepartment of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University, (Third Military Medical University)Abstract Acute kidney injury (AKI) has become a disease of global concern due to its high morbidity and mortality. This has highlighted the need for renoprotective agents. Astragaloside IV (AS-IV) is a saponin isolated from Astragalus membranaceus with good antioxidant, anti-inflammatory and anti-tumor properties. In this study, HK2 cells and rat model were utilized to explore the protective effect of AS-IV against cadmium chloride-induced oxidative stress-induced apoptosis. CdCl2-induced apoptosis, ROS production, and mitochondrial membrane potential alterations were significantly inhibited in AS-IV -treated HK2 cells. Expression of the mitochondria-associated apoptotic proteins Cleaved-Caspase3, Cleaved-Caspase9, and Cleaved-PARP was significantly reduced after AS-IV intervention. In addition, AS-IV inhibited Rat weight loss and also alleviated the symptoms of CdCl2-induced nephrotoxicity in a rat model of CdCl2-induced kidney injury. Further experiments showed that AS-IV suppresses heavy metal Cd-induced mitochondria-mediated apoptosis by regulating the Nrf2/HO-1 pathway. In conclusion, AS-IV could protect the kidney from heavy metal-induced toxicity and could be used as a nephroprotective agent.https://doi.org/10.1038/s41598-025-86312-4Acute kidney injuryAstragaloside IVHeavy metal cadmiumOxidative stressApoptosis
spellingShingle Yuchen Li
Jiayi Zhou
Tianxin Zhang
Xiaocong Li
Cheng Wu
Ziyi Zhao
Jianyuan Tang
Xiaoyu Tan
Qiongying Hu
Wenhao Liao
Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2
Scientific Reports
Acute kidney injury
Astragaloside IV
Heavy metal cadmium
Oxidative stress
Apoptosis
title Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2
title_full Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2
title_fullStr Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2
title_full_unstemmed Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2
title_short Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2
title_sort astragaloside iv attenuates cadmium induced nephrotoxicity in rats by activating nrf2
topic Acute kidney injury
Astragaloside IV
Heavy metal cadmium
Oxidative stress
Apoptosis
url https://doi.org/10.1038/s41598-025-86312-4
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