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-alpha) 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-alpha) were determined by Western blot analysis. Results: Guggulsterone significantly inhibited LPS-induced upregulation of INF-alpha 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-alpha degradation was suppressed by the guggulsterone pretreatment. Conclusions: These results show that the guggulsterone has inhibitory effect on TNF-alpha 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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.