Clinical Research

Inhibition of TNFα production and blocking of mitogen-activated protein kinase

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-b-BOSWELLIC ACID

SENGUPTA, KRISHANU & GOLAKOTI, TRIMURTULU & Marisetti, Ajitkumar & Tummala, Tejaswi & RAVADA, SURYACHANDRA & Alluri, Kr & RAYCHAUDHURI, SIBA

(2009) JOURNAL OF FOOD LIPIDS. 16. 325 – 344. 10.1111/j.1745-4522.2009.01150.x.

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-b-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-TNFa 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.

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