title: Leonurine ameliorates LPS-induced acute kidney injury via suppressing ROS-mediated NF-κB signaling pathway.
abstract: Acute kidney injury (AKI) is an abrupt loss of kidney function. Severe AKI requires renal replacement therapy and has high mortality. Leonurine (LEO), an alkaloid isolated from Leonurus cardiaca, has shown biological effects such as antioxidant, anticoagulant, and anti-apoptosis. We have examined the effect of LEO on lipopolysaccharide (LPS)-induced AKI in mice and further studied the mechanism involved. Blood urea nitrogen (BUN), creatinine and cytokine were estimated in the serum or tissue. Kidney tissue specimens were used for biochemical estimations of lipid peroxides (LPO), reduced glutathione (GSH), and reactive oxygen species (ROS). The effects of LEO on LPS-induced renal tissue damage were detected by hematoxylin and eosin (HE) stain and electron microscopy. The production of cytokines in the tissue and blood was measured by ELISA. Protein phosphorylation and protein subcellular localization were tested by Western blot. LEO is protected against LPS-induced AKI, improved animal survival and maintained the redox balance. The beneficial effects of LEO were accompanied by the down-regulation of TNF-α, IL-1, IL-6, IL-8, KIM-1 expression and by the inhibition of the phosphorylation of IκBα and p65 translocalization. These results suggest that LEO may suppress NF-κB activation and inhibit pro-inflammatory cytokine production via decreasing cellular ROS production. Accumulating studies have demonstrated that LEO reduces kidney injury and protects renal functions from LPS-induced kidney injury.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, Hefei, PR China; Department of Nephrology, Anhui Provincial Children's hospital, Hefei, PR China.
authors.forename: Daliang
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Nephrology, The First Hospital of Jiaxing, The First Hospital Affiliated of Jiaxing College, Jiaxing, PR China.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, PR China.
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Pediatrics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China. Electronic address: xg.ren74@gmail.com.
authors.forename: Xianguo
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, Hefei, PR China. Electronic address: wuyonggui1966@163.com.
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Wu
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C013587:leonurine; D008315:Malondialdehyde; D005707:Gallic Acid; D005978:Glutathione
keywords: LPS; Leonurine; NF-κB; Nephroprotective effect