title: Naringin Decreases TNF-α and HMGB1 Release from LPS-Stimulated Macrophages and Improves Survival in a CLP-Induced Sepsis Mice.
abstract: Naringin, a flavanone glycoside extracted from various plants, has a wide range of pharmacological effects. In the present study, we investigated naringin's mechanism of action and its inhibitory effect on lipopolysaccharide-induced tumor necrosis factor-alpha and high-mobility group box 1 expression in macrophages, and on death in a cecal ligation and puncture induced mouse model of sepsis. Naringin increased heme oxygenase 1 expression in peritoneal macrophage cells through the activation of adenosine monophosphate-activated protein kinase, p38, and NF-E2-related factor 2. Inhibition of heme oxygenase 1 abrogated the naringin's inhibitory effect on high-mobility group box 1 expression and NF-kB activation in lipopolysaccharide-stimulated macrophages. Moreover, mice pretreated with naringin (200 mg/kg) exhibited decreased sepsis-induced mortality and lung injury, and alleviated lung pathological changes. However, the naringin's protective effects on sepsis-induced lung injury were eliminated by zinc protoporphyrin, a heme oxygenase 1 competitive inhibitor. These results revealed the mechanism underlying naringin's protective effect in inflammation and may be beneficial for the treatment of sepsis.
authors.affiliation: Nano-Bio Resources center, Department of Cosmetic Sciences, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Minchan
authors.initials: M
authors.lastname: Gil
authors.affiliation: Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea.
authors.forename: Yun Kyu
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
authors.forename: Sang Bum
authors.initials: SB
authors.lastname: Hong
authors.affiliation: Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002432:Cecum / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D044950:Flavanones / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008026:Ligation / Q000379:methods; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D018805:Sepsis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D044950:Flavanones; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C017803:zinc protoporphyrin; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; C005274:naringin; C028610:flavanone