Unveiling the molecular mechanism of diosmin to resolve cardiovascular dysfunction and remodeling in hypertension

This study aimed to examine the potential effects and mechanisms of diosmin, a flavone glycoside, on blood pressure and cardiovascular abnormalities in a rat model of hypertension caused by renal artery stenosis. Male Sprague-Dawley rats were operated on two-kidney, one-clip (2K-1C) to induce renovascular hypertension. Following three weeks of surgery, 2K-1C rats were subjected to daily oral administration of diosmin (25 or 50 mg/kg) or telmisartan (5 mg/kg) for four weeks. Diosmin significantly reduced blood pressure and enhanced left ventricular (LV) performance and vascular endothelial function (P < .05). Diosmin also diminished left ventricular and aortic remodeling. It dramatically decreased oxidative stress markers, enhancing antioxidant enzyme activity, and nitric oxide metabolite levels (P < .05). Diosmin reduced the indicators of the classical renin-angiotensin system (RAS) while augmenting the indicators of the non-classical RAS. Diosmin modulated the expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 1 receptor, Mas receptor (MasR), and matrix metalloproteinase-9 in cardiac tissue (P < .05). Telmisartan exhibited effects comparable to those of diosmin. Molecular docking indicated that AT1R may serve as a molecular target for diosmetin, a metabolite of diosmin; nonetheless, its affinity was lower to that of telmisartan. In conclusion, diosmin markedly decreased blood pressure and enhanced cardiovascular function and remodeling, likely through the modulation of RAS and the attenuation of oxidative stress in 2K-1C hypertensive rats.