Antiglycation Activities and Common Mechanisms Mediating Vasculoprotective Effect of Quercetin and Chrysin in Metabolic Syndrome

Abstract

Multiple risk factors combine to increase the risk of vascular dysfunction in patients suffering from metabolic syndrome (MetS). The current study investigates the extent to which quercetin (Q) and chrysin (CH) protect against vascular dysfunction in MetS rats. MetS was induced by feeding rats a high-salt diet (3%) and fructose-enriched water (10%) for 12 weeks. Thoracic aorta was isolated from MetS rats and from control rats, with the latter being injured by methylglyoxal (MG). Aortae were incubated with CH and Q, and vascular reactivity was evaluated through the analysis of aortic contraction and relaxation in response to PE and ACh, respectively. The formation of advanced glycation end products (AGEs) and the free radical scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) were also evaluated following the introduction of CH and Q. The increased vasoconstriction and impaired vasodilation in MetS aortae were significantly ameliorated by Q and CH. Similarly, they ameliorated glycation-associated exaggerated vasoconstriction and impaired vasodilation produced by MG in control aortae. In addition, both Q and CH were effective in reducing the formation of AGEs and inhibition of glycosylation in response to MG or fructose treatment. Finally, Q successfully scavenged DPPH free radicals while CH showed significant vasodilation of precontracted aorta that was inhibited by L-NAME. In conclusion, Q and CH provide protection against vascular dysfunction in MetS by interfering with AGEs formations and AGEs-associated vascular deterioration, with CH being largely dependent on NO-mediated mechanisms of vasodilation.

Figure 1

Effect of (a) Q and (b) CH on isolated aorta responsiveness to PE in fructose-induced MetS after incubation with Q or CH at 37°C for 60 minutes. Results are expressed as mean ± SEM (n = 6–8). ^#p < 0.05 when compared to control, ^∗p < 0.05 when compared to MetS by two-way ANOVA followed by Bonferroni post hoc test. (c) Representative recording charts of control, MetS, MetS + Q 30 μM, and MetS + CH 30 μM experiments.

Figure 2

Effect of (a) Q and (b) CH on isolated aorta responsiveness to ACh in fructose-induced MetS after incubation with Q or CH at 37°C for 60 minutes. Results are expressed as mean ± SEM (n = 6–8). ^#p < 0.05 when compared to control, ^∗p < 0.05 when compared to MetS by two-way ANOVA followed by Bonferroni post hoc test.

Figure 3

Effect of (a) Q and (b) CH on isolated normal aorta responsiveness to PE after incubation with MG (100 μM) in the presence and absence of Q or CH at 37°C for 60 minutes. Effect of (c) Q and (d) CH on isolated normal aorta responsiveness to ACh after incubation with MG (100 μM) in the presence and absence of Q or CH at 37°C for 60 minutes. Results are expressed as mean ± SEM (n = 6–8). ^#p < 0.05 when compared to control, ^∗p < 0.05 when compared to MG by two-way ANOVA followed by Bonferroni post hoc test.

Figure 4

Effect of Q and CH on (a) AGE, (b) dityrosine, and (c) N-formyl kynurenine production upon incubation of BSA (10 mg/ml) with MG (50 mM) at 37°C for one hour. Control is a reaction mixture including only BSA while the MG reaction mixture consists of BSA with MG. AG was used as positive control. Results are expressed as mean ± SEM (n = 3). ^#p < 0.05 when compared to control, ^#p < 0.05 when compared to MG by one-way ANOVA followed by Dunnett's post hoc test.

Figure 5

Effect of Q and CH on (a) AGE, (b) dityrosine, and (c) N-formyl kynurenine production upon incubation of BSA (10 mg/ml) with F (50 mM) at 37°C for two weeks. Control is a reaction mixture including only BSA while the F reaction mixture consists of BSA with F. AG was used as positive control. Results are expressed as mean ± SEM (n = 3). ^#p < 0.05 when compared to control, ^∗p < 0.05 when compared to F by one-way ANOVA followed by Dunnett's post hoc test.

Figure 6

Effect of (a) Q and (b) CH on ROS production as initiated by DPPH (240 μM). Control is a reaction mixture including only DPPH. Results are expressed as mean ± SEM (n = 3). ^∗p < 0.05 when compared to each corresponding control by two-way ANOVA followed by Bonferroni post hoc test.

Figure 7

Direct vasorelaxation effect of the compounds (a) Q and (b) CH on PE-precontracted isolated aorta with and without incubation with L- NAME (1 mM) at 37°C for 30 minutes. Results are expressed as mean ± SEM (n = 6–8). ^∗p < 0.05 when compared to control by two-way ANOVA followed by Bonferroni post hoc test.