title: Hydroxysafflor yellow A attenuates ischemia/reperfusion-induced liver injury by suppressing macrophage activation.
abstract: Hydroxysafflor yellow A (HSYA), a major constituent in the hydrophilic fraction of the safflower plant, can retard the progress of hepatic fibrosis. However, the anti-inflammatory properties and the underlying mechanisms of HSYA on I/R-induced acute liver injury are unknown. Inhibiting macrophage activation is a potential strategy to treat liver ischemia/reperfusion (I/R) injury. In this study, we investigated the therapeutic effect of HSYA on liver I/R injury and the direct effect of HSYA on macrophage activation following inflammatory conditions. The therapeutic effects of HSYA on I/R injury were tested in vivo using a mouse model of segmental (70%) hepatic ischemia. The mechanisms of HSYA were examined in vitro by evaluating migration and the cytokine expression profile of the macrophage cell line RAW264.7 exposed to acute hypoxia and reoxygenation (H/R). Results showed that mice pretreated with HSYA had reduced serum transaminase levels, attenuated inflammation and necrosis, reduced expression of inflammatory cytokines, and less macrophage recruitment following segmental hepatic ischemia. In vitro HSYA pretreated RAW264.7 macrophages displayed reduced migratory response and produced less inflammatory cytokines. In addition, HSYA pretreatment down-regulated the expression of matrix matalloproteinase-9 and reactive oxygen species, and inhibited NF-κB activation and P38 phosphorylation in RAW264.7 cells. Thus, these data suggest that HSYA can reduce I/R-induced acute liver injury by directly attenuating macrophage activation under inflammatory conditions.
authors: Department of Physiology, Binzhou Medical University Yantai, China.
authors: Shujun
authors: S
authors: Jiang
authors: Department of Physiology, Binzhou Medical University Yantai, China.
authors: Zhen
authors: Z
authors: Shi
authors: Department of Physiology, School of Basic Medical Sciences, Wuhan University Wuhan, China.
authors: Changyong
authors: C
authors: Li
authors: Department of Physiology, Binzhou Medical University Yantai, China.
authors: Chunlei
authors: C
authors: Ma
authors: Department of Physiology, Binzhou Medical University Yantai, China.
authors: Xianyong
authors: X
authors: Bai
authors: The School of Pharmaceutical Sciences, Binzhou Medical University Yantai, China.
authors: Chaoyun
authors: C
authors: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011809:Quinones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D011809:Quinones; D017382:Reactive Oxygen Species; C085278:hydroxysafflor yellow A; D002599:Chalcone; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Hydroxysafflor yellow A; cell migration; inflammatory cytokines; liver ischemia/reperfusion injury; macrophage; reactive oxygen species