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.