Guggulsterone suppresses LPS induced inflammation of human middle ear epithelial cells (HMEEC).
OBJECTIVE
Guggulsterone is a bioactive constituent of resinous sap originating from the guggul tree, Commiphora mukul, which has been used over several thousands of years to treat various diseases, including atherosclerosis, rheumatism, and obesity. However, the effect of guggulsterone inflammatory reactions induced by lipopolysaccharide (LSP) is not known. The aim of this study was to evaluate the anti-inflammatory effect of guggulsterone on cultured human middle ear epithelial cells (HMEEC).


METHODS
The effect of guggulsterone on LPS-induced tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) expression was evaluated in HMEEC by real-time reverse transcription polymerase chain reaction (RT-PCR). LPS-induced COX-2 production and degradation of the inhibitor kB-alpha (IkB-α) were determined by Western blot analysis.


RESULTS
Guggulsterone significantly inhibited LPS-induced upregulation of TNF-α and COX-2 in a dose-dependent manner. COX-2 protein production by LPS was significantly suppressed by the guggulsterone pretreatment. Furthermore, LPS-induced IkB-α degradation was suppressed by the guggulsterone pretreatment.


CONCLUSIONS
These results show that the guggulsterone has inhibitory effect on TNF-α expression and COX-2 production and it may be mediated through its inhibition of nuclear factor-kB activation. Our findings provide an insight into the molecular mechanisms underlying the anti-inflammatory activities of guggulsterone in relationship to otitis media.
Department of Otorhinolaryngology-Head and Neck Surgery, Dongguk University, Seoul, South Korea.
Jae-Jun
JJ
Song
Seong Keun
SK
Kwon
Chang Gun
CG
Cho
Seok-Won
SW
Park
Sung-Won
SW
Chae
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D029744:Commiphora; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004432:Ear, Middle / Q000166:cytology* / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D016328:NF-kappa B / Q000378:metabolism; D010033:Otitis Media / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011282:Pregnenediones / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011282:Pregnenediones; D014409:Tumor Necrosis Factor-alpha; C023617:pregna-4,17-diene-3,16-dione; D051546:Cyclooxygenase 2