Pharmacological Effect of Quercetin in Hypertension and Its Potential Application in Pregnancy-Induced Hypertension: Review of In Vitro, In Vivo, and Clinical Studies
Table 1
Recent experimental pharmacological in vivo studies on quercetin.
Flavonoid
Animal model
Dose
Main results
Ref.
quercetin
Sprague-Dawley rats; N-nitro-L-arginine methyl ester (L-NAME) treatment to increase in blood pressure (BP)
4 g quercetin/kg diet for four days
(i) increase NOS activity (after quercetin in the absence of L-NAME), (ii) reduction in heart glutathione oxidation ratio (after quercetin with L-NAME), (iii) decrease in systolic BP (after quercetin with L-NAME)
10 mg kg−1 b.w. per day Intragastrically for three weeks
(i) reduction in systolic BP, (ii) reduction the hypertrophic remodeling in hypertension by decrease: (a) the number of vascular smooth muscle cells (b) excessive production of superoxide anion in hypertensive aorta (c) MMP (matrix metalloproteinase) activity and MMP-2 expression
50 mg kg−1; cocktail of 50 mg kg−1 quercetin + 100 mg kg−1 vit. C b.w. per day intragastrically for 14 days
In vivo: quercetin and/or vitamin C significantly decreased in the systolic, diastolic and mean arterial blood pressure (MAP) of rats from hypertensive to normotensive values Ex vivo: quercetin and/or vitamin C significantly reduced the level of oxidative stress markers (hydrogen peroxide, malondialdehyde), increased in the activities of antioxidant defence system components (glutathione peroxidase, reduced glutathione, protein thiol, and non-protein thiol)
100 mg kg−1 b.w. per day intragastrically for 14 days
In vivo: Quercetin inhibited proliferation and increased the apoptosis of pulmonary artery smooth muscle cells In vitro: Quercetin increased cyclin D1 protein levels, decreased the protein expression of cyclin B1 and Cdc2, altered the Bax/Bcl-2 ratio, reduced MMP2, MMP9, CXCR4, integrin β1, integrin α5 expression
In vivo: quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro: quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis
10 mg kg−1 b.w. per day, per os or i.p. injection for 5 weeks
Reduction in (i) systolic BP, heart rate (ii) NADPH oxidase activity (p.o.), without effect after i.p. administration (iii) protein expression of the NADPH subunits p47, NOX1, NOX4
Reduction in (i) mean pulmonary artery pressure, (ii) monocrotaline induced increase in wall thickness and wall area, (iii) monocrotaline induced increase in expression of the pulmonary artery tissues proliferating cell nuclear antigen (PCNA)
2, 10 or 25 mg kg−1 b.w. per day, per os for 7 days
(i) decrease the mean arterial pressure (10 or 25 mg kg−1), (ii) increase the sensitivity of parasympathetic component of the baroreflex, (iii) decrease the serum oxidative stress
In vivo: (i) progressive reduction in systolic BP (ii) reduction (−14%) in mean arterial BP and heart rate, (iii) reduction MDA levels in plasma Ex vivo: (i) increase in the endothelium dependent relaxation induced by acetylcholine (aorta)
In vivo: (i) reduction in systolic (by18%), diastolic (by 23%) and mean (by 21%) arterial BP; (ii) reduction of heart rate (by 12%); (iii) reduction in parameters: the heart weight index (HW/BW), the left ventricular weight index (LVW/BW) and the kidney weight index (KW/BW); (iv) tendency to increase the lumen diameter (LD) and to reduce the media thickness (MT) Ex vivo: (i) increasing the vasodilation induced by acetylcholine (aorta);
Increase in: (i) the mean capillary diameter (by 11%), (ii) capillary network density (by 23%), (iii) share of capillaries passable for erythrocytes (by 42%); Improvement of microcirculation in the cerebral cortex
100 and 300 μg kg−1 per day intragastrically for 2 weeks
(i) no effect on BP or ACE activity in SHR rats (two doses); (ii) no effect on BP in WKY rats (max. dose) (iii) reduction of ACE activity in WKY rats (max. dose)
