Butrin, Isobutrin, and Butein from Medicinal PlantButea monospermaSelectively Inhibit Nuclear Factor-κB in Activated Human Mast Cells: Suppression of Tumor Necrosis Factor-α, Interleukin (IL)-6, and IL-8

Abstract

Activation of mast cells in rheumatoid synovial tissue has often been associated with tumor necrosis factor (TNF)-␣, interleukin (IL)-6, and IL-8 production and disease pathogenesis by adjacent cell types. Butea monosperma (BM) is a well known medicinal plant in India and the tropics. The aim of this study was to examine whether a standardized extract of BM flower (BME) could inhibit inflammatory reactions in human mast cells (HMC) using activated HMC-1 cells as a model. Four previously characterized polyphenols-butrin, isobutrin, isocoreopsin, and butein-were isolated from BME by preparative thin layer chromatography, and their purity and molecular weights were determined by liquid chromatography/mass spectrometry analysis. Our results showed that butrin, isobutrin, and butein significantly reduced the phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced inflammatory gene expression and production of TNF-␣, IL-6, and IL-8 in HMC-1 cells by inhibiting the activation of NF-B. In addition, isobutrin was most potent in suppressing the NF-B p65 activation by inhibiting IB␣ degradation, whereas butrin and butein were relatively less effective. In vitro kinase activity assay revealed that isobutrin was a potent inhibitor of IB kinase complex activity. This is the first report identifying the molecular basis of the reported anti-inflammatory effects of BME and its constituents butrin, isobutrin, and butein. The novel pharmacological actions of these polyphenolic compounds indicate potential therapeutic value for the treatment of inflammatory and other diseases in which activated mast cells play a role.

Mechanistic Evaluation of Butea Monosperma Using in Vitro and in Vivo Murine Models of Bronchial Asthma

“…BBM dose dependently reduced all of these inflammatory changes, and thus, ameliorated the inflammatory conditions of bronchial asthma. Butrin, isobutrin, and butein form Butea monosperma flowers significantly reduced the phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced inflammatory gene expression and production of TNF-α, IL-6, and IL-8 in HMC-1 cells by inhibiting the activation of NF-kB suggesting anti inflammatory activity 47 . Butein isolated from flowers significantly inhibited COX-2 expression and phospho-mitogen activated protein kinase followed by inhibition in total activity of PKC suggesting the anti-inflammatory and anti-cancer activity 30 .…”

Potential anti-inflammatory bioactives from medicinal plants of Western Ghats, India

“…Taub: Butea monosperma is a well known medicinal plant in India used to treat cuts, wounds and skin diseases [52] . Anti-inflammatory activity was credited to the presence of polyphenols-butrin, isobutrin, isocoreopsin and butein [53] . All these polyphenols could significantly reduce the phorbol 12-myristate 13-acetate and calcium ionophore A23187 induced inflammatory response in HMC-1 human mast cells [53] .…”

A Comprehensive review on Pharmacological Profile of Butea monosperma (Lam.) Taub

“…Similarly, the methanolic extract of Butea monosperma stem bark exhibited anti-inflammatory activity in a dose dependant manner on carrageenan induced paw (William et al, 2007). The butrin, isobutrin, and butein isolated from Butea monosperma flowers significantly reduced the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-induced inflammatory gene expression and production of TNF-α, IL-6, and IL-8 in Human Mast Cells by inhibiting the activation of NF-kB (Rasheed et al, 2010). Similarly, butein isolated from Butea monosperma flowers significantly inhibited PMA -induced COX-2 expression in the non-tumorigenic MCF-10A and cancerous MCF-7 breast cells by inhibiting ERK and p-MAPK followed by inhibition in total activity of PKC (Lau et al, 2010).…”