Inhibition of TNFα production and blocking of mitogen-activated protein kinase/NFκB activation in lipopolysaccharide-induced THP-1 human monocytes by 3-O-acetyl-11-keto-β-boswellic acid.

Boswellia serrata resin is regarded as a potent anti-inflammatory agent in traditional and herbal medicine in the Indian subcontinent. The compound 3-O-acetyl-11-keto-β-boswellic acid (AKBA) is the most effective boswellic acid and mostly responsible for B. serrata's anti-inflammatory properties. Here, we reexamined the anti-inflammatory potential of a product selectively enriched with 30% AKBA (BE-30, also known as 5-Loxin®) and evaluated its underlying possible molecular mechanism of action. BE-30 was 42.96% more effective than regular Boswellia extract (BE-3) in inhibiting 5-lipoxygenase activity. In lipopolysaccharide (LPS)-induced THP-1 human monocytes, BE-30 showed a strong anti-TNFαactivity (half maximal inhibitory concentration 4.61 ± 0.87 µg/mL), which provides 71.14% (P < 0.001) better efficacy than BE-3. Our investigations suggest that BE-30 inhibits the LPS-induced activation of serine/threonine kinases of mitogen-activated protein kinase family, which are the key players responsible for a variety of cellular responses, including inflammation. Additionally, we also show that BE-30 blocks the LPS-induced NFκB activation by inhibiting IκBα phosphorylation and p65 translocation to the nuclear compartment of THP-1 monocytes. Collectively, these findings provide molecular basis for the anti-inflammatory properties of BE-30. PRACTICAL APPLICATIONS This article describes the underlying molecular mechanisms for the anti-inflammatory activities of an enriched formulation containing up to 30% 3-O-acetyl-11-keto-β-boswellic acid (AKBA), the active principle that is mainly responsible for Boswellia serrata's anti-inflammatory properties. This AKBA-enriched formulation (BE-30), known as 5-Loxin, is commercially available in the United States and is being used as a key ingredient of several formulations for improvement of joint health. This work explains anti-TNFα properties of BE-30 in a cellular inflammation model in vitro and its inhibitory action on MAPK pathways in inflammation and, in addition, its anti-NFκB activities. The findings will provide a further comprehensive mechanism of anti-inflammatory action of 5-Loxin at the cellular and molecular level.