Madecassoside alleviates acute kidney injury by regulating JNK-mediated oxidative stress and programmed cell death.

Autor: Shan RR; School of Life Sciences, Anhui Medical University, Hefei, 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, the Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China., Yu JT; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, the Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China., Zhang SF; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, the Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China., Xie MM; School of Life Sciences, Anhui Medical University, Hefei, 230032, China., Hou R; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, the Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China., Xie CY; School of Life Sciences, Anhui Medical University, Hefei, 230032, China., Dong ZH; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, the Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China., Yang Q; Department of Clinical Pharmacology, Second Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, Anhui, China., Hu XW; Department of Clinical Pharmacy, Anhui provincial Children's Hospital, Hefei, 230051, China., Dong YH; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, the Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China., Zhang Y; Anqing First People's Hospital of Anhui Medical University, Anqing, 246000, China., Luo XF; School of Life Sciences, Anhui Medical University, Hefei, 230032, China., Cui ZY; Second Clinical Medical College, Anhui Medical University, Hefei, 230032, China., Liu XY; School of Life Sciences, Anhui Medical University, Hefei, 230032, China; Translational Research Institute of Henan Provincial People's Hospital and People's Hospital of Zhengzhou University, Molecular Pathology Centre, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450053, China., Xie YC; Key Laboratory of Functional Small Organic Molecule Ministry of Education and Jiangxi's Key Laboratory of Green Chemistry, Key Laboratory of Protection and Utilization of Subtropic Plant Resources of Jiangxi Province, School of Life Sciences, Jiangxi Normal University, Nanchang, 330022, China., Wen JG; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, the Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China., Liu MM; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, the Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China., Jin J; Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China., Chen Q; School of Life Sciences, Anhui Medical University, Hefei, 230032, China. Electronic address: chenqi@ahmu.edu.cn., Meng XM; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, the Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China. Electronic address: mengxiaoming@ahmu.edu.cn.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Jan; Vol. 123, pp. 155252. Date of Electronic Publication: 2023 Nov 30.
DOI: 10.1016/j.phymed.2023.155252
Abstrakt: Background: Acute kidney injury (AKI) has high morbidity and mortality, which is manifested by inflammation and apoptosis. Effective treatment methods for AKI are currently lacking.
Objective: This study demonstrated the protecting effects of Madecassoside (MA) in the cisplatin- and hypoxia-reoxygenation-induced renal tubular epithelial cells in vitro and AKI mice in vivo.
Methods: In vivo AKI mouse models were established by inducing them with cisplatin and renal ischemia-reperfusion. In vitro injury models of mouse renal tubular epithelial cells were established by inducing them with cisplatin and hypoxia and reoxygenation, respectively. The mechanism of MA effects was further explored using molecular docking and RNA-sequencing.
Results: MA could significantly reduce kidney injury in the cisplatin-and renal ischemia-reperfusion (IRI)-induced AKI. Further validation in the two cellular models also showed that MA had protect effects. MA can alleviate AKI in vitro and in vivo by inhibiting inflammation, cell apoptosis, and oxidative stress. MA exhibited high permeability across the Caco-2 cell, can enter cells directly. Through RNA-seq and molecular docking analysis, this study further demonstrated that MA inhibits its activity by directly binding to JNK kinase, thereby inhibiting c-JUN mediated cell apoptosis and improving AKI. In addition, MA has better renal protective effects compared to curcumin and JNK inhibitor SP600125.
Conclusion: The results demonstrate that MA might be a potential drug for the treatment of AKI and act through the JNK/c-JUN signaling pathway.
Competing Interests: Declaration of Competing Interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.
(Copyright © 2023. Published by Elsevier GmbH.)
Databáze: MEDLINE
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