Sesamol inhibits LPS induced angiogenesis via downregulating VEGFA/VEGFR2 signalling both in vitro and in vivo

Abstract

Background: Knowing the nutritional and pharmacological significance of foods enables the deeper understanding of their role against several diseases. Sesame (Sesamum indicum) has been used in traditional Chinese medicine to combat aging and age-related diseases. Sesamol is a natural polyphenolic compound isolated from sesame seed oil that was reported to possess various therapeutic potentials including anti-inflammatory, antioxidant and anticancer properties. Pathological angiogenesis is a hallmark of many diseases such as rheumatoid arthritis, atherosclerosis, diabetic retinopathy and cancer. But the role of sesamol in angiogenesis is not yet studied. Methods: We studied the effect of sesamol on LPS induced angiogenesis using Rat Aortic Endothelial Cells (RAECs). Wound healing assay was used to study the effect of sesamol on cell migration and tube formation assay was used to evaluate the effect of sesamol on tubulogenesis. Western blot, ELISA and qPCR analysis were carried out to study the expression of proangiogenic factors such as VEGFA, VEGFR2, MMP-9 and cell adhesion molecules. Results: Sesamol downregulated the LPS induced tube formation and cell migration in RAEC. Immunoblot results suggest that sesamol has an inhibitory effect on VEGFA and VEGFR2 expression during LPS induced condition. Sesamol also downregulated the LPS induced overexpression of soluble adhesion molecules. qPCR and gelatin zymography results revealed that sesamol inhibited the expression and activity of MMP-9 along with an enhanced expression of its endogenous inhibitor TIMP-1. Conclusion: Our study showed that the antiangiogenic effect of sesamol is mediated via downregulating the proangiogenic markers VEGFA, soluble adhesion molecules and MMP-9.

Keywords

• Sesamol
• Angiogenesis
• Vascular endothelial growth factor
• Cell migration
• Tubulogenesis
• 3,4,methylene dioxy phenol