Anti‐angiogenesis effect of β‐D‐mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model

Angiogenesis is a process through which new capillaries are formed from pre‐existing ones, which contributes significantly to the pathogenesis of numerous diseases, such as cancer and chronic inflammatory disorders. The β‐D‐mannuronic acid (M2000) is a novel non‐steroidal anti‐inflammatory drug (NSAID) with immunosuppressive effects and is a matrix metalloproteinase (MMP) inhibitor. This research aimed to study the anti‐angiogenesis effects of M2000 under in vitro and in vivo models. The cytotoxic and anti‐proliferative effects of M2000 were examined using the trypan blue method and the MTT assay, respectively. The 3D collagen‐cytodex model and the chick chorioallantoic membrane (CAM) assay were then used to evaluate the anti‐angiogenesis property of M2000. Cytotoxicity assay revealed that M2000 (at concentrations of less than 100 μg/mL) had no cytotoxic effect on human umbilical vein endothelial cells (HUVECs). It was also illustrated that M2000 had little or no anti‐proliferative effect on HUVECs. In addition, the anti‐angiogenesis effects of M2000 were shown to be marginal in the in vitro model and both significant and dose‐dependent in the in vivo status. This study showed that M2000 could be considered as an anti‐angiogenic molecule which more likely exerts its activity mainly via indirect effects on endothelial cells and its anti‐inflammatory effects may partly be attributable to its anti‐angiogenic activity. Therefore, it could be recommended as a candidate for prevention and treatment of cancer, chronic inflammatory diseases, and other angiogenesis‐related disorders.