title: Carnosic acid nanoparticles suppress liver ischemia/reperfusion injury by inhibition of ROS, Caspases and NF-κB signaling pathway in mice.
abstract: Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can lead to early graft injury. However, the detailed molecular mechanism of I/R injury remains unclear. Carnosic acid, as a phenolic diterpene with function of anti-inflammation, anti-cancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, is produced by many species from Lamiaceae family. Nanoparticulate drug delivery systems have been known to better the bioavailability of drugs on intranasal administration compared with only drug solutions. Administration of carnosic acid nanoparticles was thought to be sufficient to lead to considerable inhibition of liver injury progression induced by ischemia/reperfusion. In our study, liver ischemia/reperfusion injury was established successfully with C57BL/6 animal model. 10 and 20mg/kg carnosic acid nanoparticles were injected to mice for five days prior to ischemia. After liver ischemia/reperfusion, the levels of serum AST, ALT and APL were increased, which was attenuated by pre-treatment with carnosic acid nanoparticles. In addition, carnosic acid nanoparticles inhibited ROS production via its related signals regulation. And carnosic acid nanoparticles also suppressed the ischemia/reperfusion-induced up-regulation in the pro-apoptotic protein and mRNA levels of Bax, Cyto-c, Apaf-1 and Caspase-9/3 while increased ischemia/reperfusion-induced decrease of anti-apoptotic factor of Bcl-2. Further, ischemia/reperfusion-induced inflammation was also inhibited for carnosic acid nanoparticles administration via inactivating NF-κB signaling pathway, leading to down-regulation of pro-inflammatory cytokines releasing. In conclusion, our study suggested that carnosic acid nanoparticles protected against liver ischemia/reperfusion injury via its role of anti-oxidative, anti-apoptotic and anti-inflammatory bioactivity.
authors.affiliation: Department of Interventional Radiology, Henan Provincial People's Hospital, Zhengzhou University, 7 Weiwu Rd., Zhengzhou 450003, Henan, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Liver-Gallbladder-Pancreas Surgery, Henan Provincial People's Hospital, Zhengzhou University, 7 Weiwu Rd., Zhengzhou 450003, Henan, People's Republic of China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Sun
authors.affiliation: Department of Liver-Gallbladder-Pancreas Surgery, Henan Provincial People's Hospital, Zhengzhou University, 7 Weiwu Rd., Zhengzhou 450003, Henan, People's Republic of China.
authors.forename: Guo-Yong
authors.initials: GY
authors.lastname: Chen
authors.affiliation: Department of Liver-Gallbladder-Pancreas Surgery, Henan Provincial People's Hospital, Zhengzhou University, 7 Weiwu Rd., Zhengzhou 450003, Henan, People's Republic of China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Wang
authors.affiliation: Department of Liver-Gallbladder-Pancreas Surgery, Henan Provincial People's Hospital, Zhengzhou University, 7 Weiwu Rd., Zhengzhou 450003, Henan, People's Republic of China.
authors.forename: Zhan-Tao
authors.initials: ZT
authors.lastname: Xie
authors.affiliation: Department of Liver-Gallbladder-Pancreas Surgery, Henan Provincial People's Hospital, Zhengzhou University, 7 Weiwu Rd., Zhengzhou 450003, Henan, People's Republic of China.
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Tang
authors.affiliation: Department of Liver-Gallbladder-Pancreas Surgery, Henan Provincial People's Hospital, Zhengzhou University, 7 Weiwu Rd., Zhengzhou 450003, Henan, People's Republic of China. Electronic address: weisidong450003@139.com.
authors.forename: Si-Dong
authors.initials: SD
authors.lastname: Wei
mesh_terms: D045784:Abietanes / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D045784:Abietanes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D020169:Caspases; C018381:salvin
keywords: Apoptosis; Carnosic acid nanoparticles; Inflammation; Ischemia/reperfusion injury; ROS