Curcumin Heals Indomethacin-Induced GastricUlceration by Stimulation of Angiogenesisand Restitution of Collagen Fibers via VEGFand MMP-2 Mediated Signaling

Aim:We examined the molecular mechanism of curcumin in a preventive and therapeutic model of indomethacininduced gastric ulceration with regard to angiogenic processes. Results: 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)-b 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. Innovation: Our study demonstrates that curcumin-mediated healing is associated with increased MMP-2, TGF-b, 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. Conclusion: We conclude that curcumin remodels gastric tissues by restoring the collagen architecture and accelerating angiogenesis.