Liquiritigenin, an Active Ingredient of Liquorice, Alleviates Acute Kidney Injury by VKORC1-Mediated Ferroptosis Inhibition.

Autor: Guo RZ; Research Institute of Nephrology, Zhengzhou University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Henan Province Research Center for Kidney Disease, Zhengzhou 450052, P. R. China.; Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China., Li J; Research Institute of Nephrology, Zhengzhou University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Henan Province Research Center for Kidney Disease, Zhengzhou 450052, P. R. China.; Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China., Pan SK; Research Institute of Nephrology, Zhengzhou University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Henan Province Research Center for Kidney Disease, Zhengzhou 450052, P. R. China.; Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China., Hu MY; Research Institute of Nephrology, Zhengzhou University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Henan Province Research Center for Kidney Disease, Zhengzhou 450052, P. R. China.; Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China., Lv LX; Research Institute of Nephrology, Zhengzhou University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Henan Province Research Center for Kidney Disease, Zhengzhou 450052, P. R. China.; Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China., Feng Q; Research Institute of Nephrology, Zhengzhou University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Henan Province Research Center for Kidney Disease, Zhengzhou 450052, P. R. China.; Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China., Qiao YJ; Blood Purification Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China., Duan JY; Research Institute of Nephrology, Zhengzhou University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Henan Province Research Center for Kidney Disease, Zhengzhou 450052, P. R. China.; Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China., Liu DW; Research Institute of Nephrology, Zhengzhou University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Henan Province Research Center for Kidney Disease, Zhengzhou 450052, P. R. China.; Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China., Liu ZS; Research Institute of Nephrology, Zhengzhou University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.; Henan Province Research Center for Kidney Disease, Zhengzhou 450052, P. R. China.; Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, P. R. China.
Jazyk: angličtina
Zdroj: The American journal of Chinese medicine [Am J Chin Med] 2024; Vol. 52 (5), pp. 1507-1526. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1142/S0192415X24500599
Abstrakt: Acute kidney injury (AKI) is a major public health problem worldwide that still lacks effective treatments. Recent studies have suggested that ferroptosis is a key mediator of AKI due to its activation of lipid peroxidation. Therefore, we hypothesized that antiferroptosis agents might be a novel potential therapeutic strategy for AKI. Herein, we demonstrated that liquiritigenin (LG), an active ingredient of liquorice, improves renal function by inhibiting vitamin K epoxide reductase complex subunit 1 (VKORC1)-mediated ferroptosis, both in vivo and in vitro . In a folic acid-induced murine AKI model, after a single pre-treatment intravenous injection, LG markedly alleviated the loss of renal function through suppressing ferroptosis induced by iron accumulation. LG prevented mitochondrial morphological changes and upregulated glutathione and glutathione peroxidase 4 levels, while downregulating malonaldehyde and divalent iron levels. An in vitro RNA-sequence analysis suggested that the protective role of LG may involve upregulation of VKORC1. Moreover, knockdown of VKORC1 diminished the renal protective and antiferroptosis roles of LG. Collectively, our findings demonstrated that LG protected against AKI by inhibiting VKORC1-mediated ferroptosis. This suggests that inhibiting ferroptosis might be a novel therapeutic approach in the future.
Databáze: MEDLINE
Externí odkaz: