Protective and anti-angiopathy effects of caffeic acid phenethyl ester against induced type 1 diabetes in vivo

Objective: This study aims at investigating the anti-diabetic effects of caffeic acid phenethyl ester (CAPE) against induced immunoregulated diabetes in vivo. Methods: Swiss mice were administered cyclosporine (CsA) 20 mg/kg/day, s.c. for 10 days and simultaneously received multiple low doses of streptozotocin (MLDSTZ) 40 mg/kg/day, i.p. for 5 consecutive days. Results: Our results showed that administering CAPE (5 mu M/kg Ip/every 2 days) to diabetic mice led to a time-dependent decrease in blood glucose levels to 137.1 +/- 72 from 229.1 +/- 12.6 mg/dl and induced a significant increase in serum insulin levels by 93.8% compared with untreated ones. An in vivo anti-inflammatory effect of CAPE treated diabetic mice was observed, based on a significant decrease in IL-1 beta and IFN-gamma (P < 0.01) levels and a highly significant reduction in NO (P < 0.001). An anti-angiogenic effect of CAPE was observed, as determined by a significant serum matrix metalloproteinase (MMP-9) reduction, angiopoietin (Ang-2) reduction and activation of endostatin serum level in the CAPE treated diabetic mice. Furthermore, histopathological examination showed that destroyed pancreatic islets were regenerated and became free of cell infiltration after treatment Conclusion: CAPE has a significant anti-diabetic effect on mice in vivo. This anti-diabetic effect may be related to its anti-inflammatory and angiostatic effects. It also reduced angiogenic factors which may shift the equilibrium to the angiostatic effect of CAPE. These findings provide the validity of CAPE as anti-diabetic agent in the special model of CsA/STZ and could be relevant in the future for human diabetes. (C) 2013 Elsevier B.V. All rights reserved.