title: Icaritin exhibits anti-inflammatory effects in the mouse peritoneal macrophages and peritonitis model.
abstract: Icaritin, an intestinal metabolite of prenylflavonoids from Herba Epimedii, has been known to regulate many cellular processes. The purpose of this study was to investigate the protective effects of icaritin on inflammation in lipopolysaccharide (LPS) stimulated mouse peritoneal macrophages in vitro and zymosan induced peritonitis model in vivo. The release of Nitric oxide (NO) was measured by a Griess reagent system. The phagocytosis, the expression of CD69, the production of inflammatory cytokines and the leukocytes numbers were determined by flow cytometry. The Ca(2+) influx was recorded by confocal microscopy. The phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) was determined by Western blot. The results showed that icaritin significantly inhibited the NO, IL-6, IL-10 TNF-α, and MCP-1 production both in vitro and in vivo. Icaritin efficiently diminished the uptake of nonopsonized pHrodo™-labeled Escherichia coli bacteria on the LPS-stimulated macrophages. In addition, icaritin significantly inhibited the expression of CD69 on CD11b(+) macrophages. Icaritin pretreatment significantly inhibited the elevation of intracellular Ca(2+) induced by LPS. Furthermore, icaritin markedly decreased phospho-p38 and JNK protein expression in LPS-stimulated mouse peritoneal macrophages. In vivo study, it was also observed that icaritin prolonged survival of peritonitis mice, and inhibited massive leukocyte influx into the peritoneal cavity. These results suggest that icaritin possesses significant anti-inflammatory effects that may be mediated through the regulation of inflammatory cytokines and phosphorylation of p38 and JNK.
authors.affiliation: Experimental Technology of Center, Jinan University, Guangzhou, PR China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Lai
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Ye
authors.forename: Chenghong
authors.initials: C
authors.lastname: Sun
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Huang
authors.forename: Xiangao
authors.initials: X
authors.lastname: Tang
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Zeng
authors.forename: Pinghe
authors.initials: P
authors.lastname: Yin
authors.forename: Yaoying
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D037181:Lectins, C-Type / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010538:Peritonitis / Q000188:drug therapy* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D000099192:CD69 Antigens
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium; D005419:Flavonoids; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D009569:Nitric Oxide; D000099192:CD69 Antigens; C499403:icaritin