title: Didymin ameliorates hepatic injury through inhibition of MAPK and NF-κB pathways by up-regulating RKIP expression.
abstract: A flavone was isolated from Origanum vulgare and identified as didymin (O. vulgare didymin, OVD). The protective effect and mechanism of OVD on acute liver injury was then assessed in vivo and in vitro. Our results showed that OVD significantly alleviated CCl4-induced liver injury in mice and markedly decreased serum ALT and AST activities. OVD treatment significantly reduced CYP2E1 activity, lipid peroxidation level, ROS generation, NO production and pro-inflammatory cytokines (such as TNF-α, IL-6 and IL-1β) in liver tissues and RAW 264.7 cells, but enhanced the hepatic antioxidative enzymes activities. Further study showed that OVD significantly inhibited the NF-κB and MAPK pathways. Interestingly, OVD notably enhanced Raf kinase inhibitor protein (RKIP) expression, and the effects of OVD on histological changes, oxidative stress and inflammation was largely abolished by the RKIP specific inhibitor locostatin. Our findings indicate that OVD can ameliorate CCl4-induced liver injury, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of MAPK and NF-κB signaling pathways.
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Facheng
authors.initials: F
authors.lastname: Bai
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Nie
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Shengjuan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Chunyuang
authors.initials: C
authors.lastname: Lu
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Xunshuai
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 169483, Singapore.
authors.forename: Lang
authors.initials: L
authors.lastname: Zhuo
authors.affiliation: Guangxi Medical University, Nanning 530021, China. Electronic address: gxLx60@163.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005419:Flavonoids / Q000627:therapeutic use*; D006027:Glycosides / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D031341:Origanum; D023303:Oxazolidinones / Q000494:pharmacology; D049488:Phosphatidylethanolamine Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005419:Flavonoids; D006027:Glycosides; D018836:Inflammation Mediators; D023303:Oxazolidinones; D049488:Phosphatidylethanolamine Binding Protein; C539308:Raf kinase inhibitory protein, mouse; D017382:Reactive Oxygen Species; C552234:didymin; C529490:locostatin; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Didymin; MAPK pathway; NF-κB pathway; RKIP