Curcumin Heals Indomethacin-Induced Gastric Ulceration by Stimulation of Angiogenesis and Restitution of Collagen FibersviaVEGF and MMP-2 Mediated Signaling

We examined the molecular mechanism of curcumin in a preventive and therapeutic model of indomethacin-induced gastric ulceration with regard to angiogenic processes.Disrupted blood vessels, reduced collagen matrices, and significant (60%) injury to mucosal cells were observed during ulceration. In addition, ulcerated tissues exhibited decreased matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) expression in blood vessels. Interestingly, curcumin blocked ulceration by induction of collagenization and angiogenesis in gastric tissues via upregulation of MMP-2, membrane type (MT) 1-MMP, VEGF, and transforming growth factor (TGF)-β at protein and messenger ribonucleic acid (mRNA) levels. To examine the angiogenic properties of curcumin, we employed a chorioallantoic membrane model and Matrigel assay. During healing, curcumin promoted collagenization and angiogenesis as well as enhanced MMP-2 activity via positive MT1-MMP regulation and negative tissue inhibitor of metalloproteinase-2 regulation.Our study demonstrates that curcumin-mediated healing is associated with increased MMP-2, TGF-β, and VEGF expression and that it plays a pivotal role as an angiogenic modulator by stimulating vascular sprout formation and collagen fiber restoration in ulcerated tissues.We conclude that curcumin remodels gastric tissues by restoring the collagen architecture and accelerating angiogenesis.