Imperatorin ameliorates ferroptotic cell death, inflammation, and renal fibrosis in a unilateral ureteral obstruction mouse model.

Autor: Yang JD; Division of Urology, Department of Surgery, National Yang-Ming Chiao Tung University Hospital, Yilan, Taiwan., Lin SC; Department of Nutrition, China Medical University, Taichung 40402, Taiwan., Kuo HL; Division of Nephrology, Department of Internal Medicine, China Medical University Hospital, Taichung 40402, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan; Clinical Nutrition, China Medical University Hospital, Taichung 40402, Taiwan., Chen YS; Department of Nutrition, China Medical University, Taichung 40402, Taiwan., Weng PY; Department of Nutrition, China Medical University, Taichung 40402, Taiwan., Chen CM; Division of Neurosurgery, Department of Surgery, College of Medicine and Hospital, National Taiwan University, Taipei 10051, Taiwan., Liu SH; Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan., Huang CF; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan; Department of Nursing, College of Medical and Health Science, Asia University, Taichung, 413, Taiwan., Guan SS; Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan 32546, Taiwan., Liao PL; Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University-Yang ming Campus, 155, Sec. 2, Linong Street, Taipei 11221, Taiwan., Su YH; Department of Surgery, Division of General Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei 235, Taiwan; Department of General Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan., Lee KI; Department of Emergency, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan., Wang PY; Department of Nutrition, China Medical University, Taichung 40402, Taiwan., Chuang HL; Department of Emergency, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan. Electronic address: tc2050403@tzuchi.com.tw., Wu CT; Department of Nutrition, China Medical University, Taichung 40402, Taiwan. Electronic address: ct-wu@mail.cmu.edu.tw.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Dec; Vol. 135, pp. 156066. Date of Electronic Publication: 2024 Sep 16.
DOI: 10.1016/j.phymed.2024.156066
Abstrakt: Background: Imperatorin is a naturally occurring furocoumarin derivative found in traditional Chinese medicine Angelica dahurica for its anticancer, antihypertensive, and antidiabetic properties. Chronic kidney disease (CKD) is a global health issue, characterized by a high prevalence, significant morbidity and mortality, and a range of related complications.
Objective: This study aims to investigate the protective effects of imperatorin treatment and the specific underlying mechanisms in progressive CKD.
Methods: Imperatorin was orally administrated for 14 consecutive days to mice with unilateral ureteral obstruction (UUO) to investigate the renal pathological alternations, pro-inflammatory mediators, antioxidant response, and ferroptotic death signaling. Imperatorin was also tested in the erastin-induced injury of renal proximal tubular cells (NRK-52E). Cell viability, ferroptosis protein markers, erastin-induced oxidative stress, and lipid peroxidation were assessed.
Results: In vivo, imperatorin treatment alleviated kidney histology alternations and attenuated the protein expression of fibrotic markers. Furthermore, imperatorin administration reduced inflammatory cell infiltration, and alleviated the oxidative stress burden by downregulating protein markers such as catalase, superoxide dismutase 2 (SOD-2), NADPH oxidase 4 (NOX-4), and thioredoxin reductase 1 (Trxr-1). It also mitigated ferroptosis markers such as glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11/cystine transporter (SLC7A11/xCT), and transferrin receptor 1 (TFR-1), and attenuated renal cell apoptosis. In vitro, imperatorin treatment effectively decreased erastin-induced feroptotic cell death, restored the antioxidant enzyme levels, and mitigated lipid peroxidation as well as the expression of ferroptosis-related markers (XCT, GPX4, and p-p53) in a dose-dependent manner.
Conclusion: Our finding demonstrated for the first time, that imperatorin treatment holds therapeutic potential in a UUO mouse model of CKD and inhibits the erastin-induced oxidative stress, ferroptosis, and subsequent lipid peroxidation in vitro. This highlights the potential of imperatorin as a future therapeutic target for ferroptosis to improve the progression of CKD.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper
(Copyright © 2024. Published by Elsevier GmbH.)
Databáze: MEDLINE
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