Abstract |
Diosmetin is a citrus flavonoid that has antioxidant and anti-inflammatory effects. This
study examined the effect of diosmetin on blood pressure and vascular alterations and its
underlying mechanisms in experimentally hypertensive rats. Male Sprague rats were administered
Nω-nitro-L-arginine methyl ester L-NAME for five weeks and were given diosmetin at doses of 20
or 40 mg/kg or captopril (5 mg/kg) for two weeks. Diosmetin alleviated hypertension, improved
endothelial dysfunction, and suppressed the overactivity of sympathetic nerve-mediated
vasoconstriction in aorta and mesentery hypertensive rats (p < 0.05). Increases in plasma and aortic
tissue malondialdehyde (MDA) and carotid superoxide generations and reductions of plasma
superoxide dismutase, catalase, and nitric oxide in hypertensive rats were ameliorated by diosmetin
(p < 0.05). Diosmetin increased the protein expression of nuclear factor erythroid 2-related factor 2
(Nrf2) and heme oxygenase-1 (HO-1) in hypertensive rats. Furthermore, diosmetin mitigated
hypertrophy and collagen accumulation of the aortic wall in L-NAME rats. It exhibited an antiinflammatory effect by reducing interleukin-6 (IL-6) accumulation and by overexpressing the
phospho-c-Jun N-terminal kinases (p-JNK) and the phospho-nuclear factor-kappaB (p-NF-κB)
proteins in the aorta (p < 0.05). Captopril was a positive control substance and had similar effects to
diosmetin. In summary, diosmetin reduced blood pressure and alleviated vascular abnormalities in
L-NAME-treated rats. These effects might be related to antioxidant and anti-inflammatory effects
as well as to the modulation of the expression of the Nrf2/HO1 and p-JNK/NF-κB proteins |