Effects of a flavonoid-enriched orange peel extract against type 2 diabetes in the obese ZDF rat model

Effects of an enriched orange peel extract(OPE)against type 2 diabetes(T2D)were analyzed in ZDF rats which were hyperglycemic,dyslipidemic and express pro-inflammatory markers.Glucose related parameters were lowered in the lean control and metformin group as compared to ZDF vehicle controls.OPE was well tolerated and induced a decline in fasted blood glucose and increase levels of fed glucose although to a lesser degree as compared to metformin.However,OPE did not improve glucose tolerance but showed significantly elevated glucose levels.Furthermore,OPE treatment caused an increase of free fatty acids in a dose-responsive manner as well as elevated levels of cholesterol and LDL.The analysis of inflammatory mediators revealed a significant down-regulation of COX-2,ICAM-1,and TNF-˛in epididymal adipose tissue in response to OPE to a higher degree as compared to ibuprofen.In whole blood,IL-4 was upregulated in a dose-responsive manner as measured by ELISA.In summary,lipophilic OPE showed strong anti-inflammatory effects in adipose tissue,ambivalent effects against hyperglycemia,whereas hyperlipidemia was increased.Our study emphasize the complexity of anti-diabetic regimen suggesting a treatment with OPE to reduce inflammation in adipose tissue in combination with antidiabetic therapeutics as promising strategy against T2D.