Inhibition of TNF-α induced ICAM-1, VCAM-1 and E-selectin expression by Momordica charantia L.

Abstract

The initiation of an atherosclerotic lesion involves establishment of an endothelial cell pro-inflammatory state that recruits leukocytes and promotes their movement across the endothelium. These processes require endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-leukocyte adhesion molecule-1 (E-selectin). Tumor necrosis factor-α (TNF-α) is a powerful inducer of these adhesion molecules [1]. The fruit of Momordica charantia L. (MC) is a common vegetable in tropical areas of Asia and Africa. MC also has been traditionally used as a bitter stomachic and an antidiabetic [2]. Experiments were performed to test whether MC alters TNF-α-induced expression of these adhesion molecules. Human umbilical vein endothelial cells (HUVEC) were treated for 18h with or without an extract and fractions of MC and TNF-α. ICAM-1, VCAM-1 and E-selectin were detected by cell-based ELISA, Western blots and RT-PCR. MC significantly inhibited TNF-α-induced expression of each adhesionα molecule in a dose-dependent manner. The chloroform fraction of MC significantly inhibited TNF-α-induced expression of each adhesion molecule in a dose-dependent manner. Nuclear factor-κB (NF-κB) is required for transcription of ICAM-1, VCAM-1 and E-selectin adhesion molecule genes [3]. Western blot analysis revealed that the chloroform fraction of MC inhibits translocation of the p65 subunit of NF-κB to the nucleus. Thus, the chloroform fraction of MC inhibited TNF-α-mediated induction of ICAM-1, VCAM-1 and E-selectin in HUVEC by inhibiting NF-κB, and lipophilic components of MC may suppress inflammation and modulate the immune response.