Chrysin and Luteolin Alleviate Vascular Complications Associated with Insulin Resistance Mainly Through PPAR-γ Activation

Chrysin and luteolin are two flavonoids with Peroxisome proliferators-activated receptor gamma (PPAR-gamma) stimulating activity. Here, we investigated the protective effect of chrysin and luteolin from vascular complications associated with insulin resistance (IR). IR was induced in rats by drinking fructose for 12 weeks while chrysin and luteolin were given for 6 weeks with or without PPAR-gamma antagonist, bisphenol A diglycidyl ether (BADGE). Then, blood pressure (BP) was recorded and serum levels of glucose, insulin, advanced glycation end products (AGEs) and lipids were measured. Concentration response curves for phenylephrine (PE), KCl, and acetylcholine (ACh) were obtained in thoracic aorta rings. Aortic reactive oxygen species (ROS) and nitric oxide (NO) generation were also studied. Chrysin and luteolin significantly alleviated systolic BP elevations caused by IR, while the co-administration of BADGE prevented chrysin alleviation. Although, neither chrysin nor luteolin affected ACh impaired vasodilatation, they both alleviated exaggerated vasoconstrictions to PE and KCl in IR animals. In addition, incubation of the aorta from IR animals with chrysin or luteolin prevented exaggerated vasoconstrictions to PE and KCl. On the other hand, co-administration of BADGE or co-incubation with GW9662, the selective PPAR-gamma antagonist, prevented chrysin alleviation. Both chrysin and luteolin inhibited the developed hyperinsulinemia and increases in serum AGEs, lipids while, BADGE reduced the effect of chrysin on hyperinsulinemia and dyslipidemia. Chrysin and luteolin markedly inhibited elevated NO and ROS in IR aortae while BADGE did not change their effect on NO and ROS. In conclusion, chrysin and luteolin alleviate vascular complications associated with IR mainly through PPAR-gamma dependent pathways.