Pentacyclic triterpenoids from Boswellia serrata inhibit NFκB activation and TNF-α release. Implications for the treatment of chronic inflammatory diseases

In traditional Ayurvedic medicine extracts from the oleogum resin from Boswellia serrata have been used for the treatment of various chronic inflammatory diseases. Such extracts have been successfully employed in clinical pilot studies for the treatment of ulcerative colitis and rheumatoid arthritis.

We have isolated and characterized various acetyl-boswellic acids (ABA), which constitute the active principle of Boswellia serrata extracts.

Proinflammatory cytokines such as tumor necrosis factor (TNF)-α are prevalent at the sites of chronic inflammation, where they are critically involved in the chronification process. Specifically TNF-α has been identified as highly relevant pharmacotherapeutic target. The expression of cytokines including TNF-α is tightly regulated by transcription factors including NF-κB. Here we show that in endotoxin (LPS)-activated human monocytes ABA inhibit the TNF-α expression through inhibition of the NF-κB signaling. The activity of other transcription factors remained unaffected implying specificity. ABA had no effect on the binding of NF-κB proteins to DNA binding sites as analyzed by surface plasmon resonance. Instead, ABA inhibited the LPS-induced degradation of the NF-κB inhibitor and the translocation of NF-κB to the nucleus. Further, ABA inhibited the IκB kinases (IKK), which are crucial for the activation of NF-κB. Thus, via their direct inhibitory effects on IKK, ABA exert inhibition of NF-κB and subsequent the down-regulation of TNF-α expression in LPS-activated human monocytes.

These findings provide a novel molecular basis for the anti-inflammatory properties ascribed to drugs containing boswellic acids and suggest that ABA might be used for treatment of chronic inflammation.