APIGENIN RESTORES NORMAL VASCULAR REACTIVITY IN DIABETIC RATS VIA PROTEIN KINASE C INHIBITION

Abstract

Deterioration of vascular reactivity has pivotal role in diabetic vascular complications. Apigenin is a natural flavonoid with protein kinase C inhibiting activity and antioxidant effect.
Objective: In the present study, the effect of the flavonoid apigenin on diabetes-induced deteriorated vascular reactivity was investigated.
Materials and methods:Insulin deficiency was induced by streptozotocin while, insulin resistance (IR) by fructose. Rats were left tenor twelve weeks after STZ or fructose administration respectively, isolated thoracic aorta reactivity to phenylephrine (PE), KCl, acetylcholine (ACh) and sodium nitroprusside (SNP) was studied.
Results: Insulin deficiency increased responses to PE and KCl, decreased response to ACh but not affect response to SNP, while incubation with apigenin (7μM, 20min) normalized responses to PE, KCl andACh. In addition, insulin resistance (IR) increased responses to PE and KCl, decreased response to ACh but not affect the response to SNP, while in vitro incubation with apigenin normalized responses to PE, KCl and ACh. Furthermore, , protein kinase C stimulation by incubation with phorbol 12-myristate 13-acetate (PMA, 800nM, 1h) led to a similar impairment in isolated normal aorta to that seen in case of insulin deficiency and insulin resistance while co-incubation with apigenin restored normal vascular reactivity.
Discussion and conclusion: Apigenin, a natural protein kinase C inhibitor, restores normal vascular reactivity in diabetes via a mechanism involving PKC inhibition.
Key words: Diabetes; insulin resistance, aorta; contraction, relaxation; apigenin.
Abbreviations: ANOVA, analysis of variance; NO, nitric oxide; PE, phenylephrine; ROS, reactive oxygen species; SNP, sodium nitroprusside; PMA, phorbol 12-myristate 13-acetate;PKC, protein kinase C