Title : The extracts from wild bitter gourd fruit reduced the expression of inflammatory cytokines in TNF treated pulmonary epithelial cells via the PI3K AKT NF KB pathway
Abstract:
Wild bitter gourds (WBG, Momordica charantia L.) is eaten as a vegetable and used as a traditional herb in Asia. The significant pharmacological properties of WBG fruit extract (WBGE) are anti-diabetic, antiinflammatory, anti-tumor and anti-oxidant actions. However, the anti-inflammatory effects of WBGE on human lung epithelial cells and their underlying mechanisms require further investigation. To analyze the effect of WBGE and charantin on ICAM-1 and IL-6 expression under inflammation, pre-incubated A549 cells with WBGE for 24 h, 10, 30, 50, or 80 μg/mL or charantin, 0.5, 1, 3, 5 μg/mL followed by 3 ng/mL TNF-α was stimulated for 4 h. TNF-α treatment significantly increased the expression of ICAM-1 and IL-6 in A549 cells. Pretreatment with WBGE or charantin or aspirin (positive control) inhibited this effect. WBGE significantly reduced the expression of inflammatory cytokines in a concentration-dependent manner. Consistently, fluorescence microscopy images showed that ICAM-1 and IL-6 were strongly present in the cytosol of TNFα-treated A549 cells. In contrast, ICAM-1 expression was weaker in TNF-α-stimulated A549 cells pretreated with WBGE or charantin. Inhibition of PI3K / AKT phosphorylation mediates the reduction of ICAM-1 and IL-6 expression by WBGE in TNF-α-treated A549 cells. Inhibition of NF-κB p65 activation and translocation mediates the expression of ICAM-1 and IL-6 in WBGE-reduced TNF-α-treated A549 cells. WBGE reduced ICAM-1 and IL-6 expression in lung tissue of TNF-α treated WT mice. These results indicate that WBGE reduces the expression of inflammatory cytokines in both in vitro and in vivo conditions. The protective part is mediated through the PI3K / AKT / NF-κB pathway