Abstract
This study aims at investigating the anti-diabetic effects of caffeic acid phenethyl ester (CAPE) against induced immunoregulated diabetes in vivo.
Swiss mice were administered cyclosporine (CsA) 20mg/kg/day, s.c. for 10days and simultaneously received multiple low doses of streptozotocin (MLDSTZ) 40mg/kg/day, i.p. for 5 consecutive days.
Our results showed that administering CAPE (5μM/kg i.p./every 2days) to diabetic mice led to a time-dependent decrease in blood glucose levels to 137.1±7.2 from 229.1±12.6mg/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-1β and IFN-γ (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.
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.
•CAPE has anti-diabetic effects, anti-inflammatory and immunomodulatory properties.•Induced MMP-9 reduction and Endostatin elevation CAPE reduce of Ang-2 levels, which may consider as an independent predictor in treatment of diabetes.