Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNFα, IL-1β, NO and MAP kinases

Abstract

The aim of the present study is to probe the anti-inflammatory potential of the plant Boswellia serrata by studying the effect of the crude extract and the pure compound isolated from it on key inflammatory mediators like TNFα, IL-1β, and NO thus enabling the understanding of the key signaling events involved. The crude methanolic extract and the pure compound were analysed for their inhibitory effect on TNFα, IL-1β and IL-6. The results demonstrated that all three cytokines are down regulated when PBMCs are cultured in the presence of crude extract or the pure compound at various time points. Observations on Th1/Th2 cytokines revealed marked down regulation of Th1 cytokines IFNγ and IL-12 while the Th2 cytokines IL-4 and IL-10 were up regulated upon treatment with crude extract and pure compound. The extract and the pure compound isolated also showed considerable inhibition of NO production in activated RAW 264.7 cells, possibly via suppression of inducible NO synthase mRNA expression. Further to elucidate the underlying mechanism of action the effect of 12-ursene 2-diketone on LPS-induced activation of MAPK has also been examined. Our results demonstrated that 12-ursene 2-diketone inhibits the expression of pro-inflammatory cytokines and mediators via inhibition of phosphorylation of the MAP kinases JNK and p38 while no inhibition was seen in ERK phosphorylation in LPS-stimulated PBMCs. The above study therefore indicates that the crude methanolic extract and the isolated pure compound are capable of carrying out a natural anti-inflammatory activity at sites where chronic inflammation is present by switching off the pro-inflammatory cytokines and mediators, which initiate the process.