Momordica charantia (bitter melon) extracts promote angiogenesis in vitro via the receptor for advanced glycation endproducts (RAGE)

Diabetes mellitus increases oxidative stress and formation of advanced glycation endproducts (AGEs) both of which underlie vascular complications by interfering with angiogenesis required for wound-healing. Momordica charantia (MC) prevents AGE formation and promotes diabetic wound-healing in animals. This study investigates the effects of MC pulp (MCP), flesh (MCF) and charantin using an in vitro model of angiogenesis. Cultured bovine aortic endothelial cells were exposed to bovine serum albumin (BSA)-derived AGEs. MC extracts increased cell proliferation, migration (using wound-healing assay) and tube formation (using Matrigel™-embedded 3D culture) in a dose-dependent manner, and these effects were associated with increases p-ERK1/2 signaling. These effects were inhibited by MCP, MCF and charantin extracts. Blocking the receptor for AGEs (RAGE) inhibited the MC extract-induced ERK1/2 phosphorylation and tube formation, indicating the crucial role of RAGE in MC pro-angiogenic effects. In conclusion, MC extracts and charantin exert direct pro-angiogenic effects mediated through RAGE with inhibitory activity on anti-angiogenic effects of BSA-AGEs. Further studies are needed to understand the therapeutic potential of MC extracts in diabetic wound-healing.