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

Abstract

ABSTRACT 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‐TNF α activity (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.