Fermented bitter gourd extract differentially regulates lipopolysaccharide-induced cytokine gene expression through nuclear factor-κB and interferon regulatory factor-1

Abstract

Bitter gourd is the fruit of a tropical vine in Asia, Africa, and South America where it is commonly used in traditional medicine. Our study tested the effects of a fermented extract of the bitter gourd on the inflammatory activities of the human monocytic leukemia cell line, THP-1. Treatment with the extract resulted in the suppression of phagocytic as well as lipopolysaccharide (LPS)-induced adhesion activity. Interestingly, the LPS-induced expression of matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) was suppressed by the extract while the expression of Interleukin-8 (IL-8) was upregulated. The extract inhibited the LPS-induced activation of p38 mitogen-activated protein kinase (MAPKs) and nuclear factor-κB (NF-κB), both of which are well known to be required for the expression of MMP-9 and TNF-α. In contrast, the expression of interferon regulatory factor (IRF) 1, a transcription factor involved in the expression of IL-8, but not TNF-α, was enhanced by the extract. Suppression of IRF-1 expression resulted in the elimination of the extract's interleukin-8 (IL-8) enhancing effect. These results indicate that the fermented bitter gourd extract has general anti-inflammatory effects, with a differential effect on the expression of cytokines through modulation of NF-κB and IRF-1 activities.