Kaempferol is a natural flavonoid compound that exhibits various pharmacological actions. However, there are few reports regarding the role of kaempferol in cardiovascular abnormalities. This study aimed to assess whether kaempferol could prevent cardiovascular malfunction and hypertrophy provoked by chronic inhibition of nitric oxide (NO) formation in rats. Rats (180-200 g) were treated daily with N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME) (40 mg/kg, in drinking water) for five weeks concomitant with kaempferol (oral administration) at a dose of 20 mg/kg or 40 mg/kg or lisinopril (5 mg/kg). Kaempferol partially prevented the progression of hypertension provoked by NO inhibition (p < 0.05). Left ventricular malfunction and hypertrophy present in hypertensive rats were alleviated by concurrent administration of kaempferol (p < 0.05). Furthermore, L-NAME rats had increased sympathetic nerve-mediated vasoconstriction and decreased acetylcholine-induced vasorelaxation and aortic wall thickening, which were resolved by kaempferol treatment (p < 0.05). Kaempferol restored tissue superoxide formation, malondialdehyde, catalase activity, plasma nitric oxide metabolites, tumor necrosis factor-alpha (TNF-α) and interleukin-6 in L-NAME rats (p < 0.05). Overexpression of tumor necrosis factor receptor 2 (TNFR2), phosphatidylinositol 3-kinases (PI3K), AKT serine/threonine kinase 1 (Akt1) and smad2/3 in heart tissue and upregulation of tumor necrosis factor receptor 1 (TNFR1), phosphorylated nuclear factor-kappaB (p-NF-κB) and transforming growth factor beta 1 (TGF-β1) in vascular tissue were suppressed by kaempferol (p < 0.05). In conclusion, kaempferol exerts antihypertensive, cardioprotective, antioxidant, and anti-inflammatory effects in NO-dependent hypertensive rats. The underlying mechanisms of kaempferol in preventing cardiovascular changes induced by L-NAME were due to the suppression of the TNF-α pathway.

In this study, we examine whether Clitoria ternatea Linn. (CT) can prevent Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced cardiac and vascular dysfunction in rats. Male Sprague Dawley rats were given L-NAME (40 mg/kg, drinking water) and orally administered with CT extract (300 mg/kg/day) or lisinopril (2.5 mg/kg/day) for 5 weeks. The main phytochemical components of the CT extract were found to be flavonoids. The CT extract alleviated the high blood pressure in rats receiving L-NAME. Decreased vasorelaxation responses to acetylcholine and enhanced contractile responses to sympathetic nerve stimulation in aortic rings and mesenteric vascular beds of L-NAME treated rats were ameliorated by CT extract supplementation. Left ventricular hypertrophy and dysfunction were developed in L-NAME rats, which were partially prevented by CT extract treatment. The CT extract alleviated upregulated endothelial nitric oxide synthase expression, decreased plasma nitrate/nitrite levels, and increased oxidative stress in L-NAME rats. It suppressed high levels of serum angiotensin-converting enzyme activity, plasma angiotensin II, and cardiac angiotensin II type 1 receptor, NADPH oxidases 2, nuclear factor-kappa B, and tumor necrosis factor-alpha expression. The CT extract, therefore, partially prevented L-NAME-induced hypertension and cardiovascular alterations in rats. These effects might be related to a reduction in the oxidative stress and renin–angiotensin system activation due to L-NAME in rats.

Genistein is an isoflavone found in soybeans. This study evaluates the protective effects of genistein on N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension, cardiac remodeling, and dysfunction in rats. Male Wistar rats were treated with L-NAME 40 mg/kg/day together for 5 weeks, with or without genistein at a dose of 40 or 80 mg/kg/day or lisinopril 5 mg/kg/day (n = 8 per group). Genistein prevented L-NAME-induced hypertension in rats. Increases in the left ventricular weight, metalloproteinase-2, metalloproteinase-9, and collagen type I intensity were observed in L-NAME rats, and these changes were attenuated in the genistein-treated group. Genistein reduced circulating angiotensin-converting enzyme activity and angiotensin II concentrations in L-NAME rats. L-NAME increased plasma and cardiac malondialdehyde and vascular superoxide generations, as well as reductions of serum and cardiac catalase activities in rats. Plasma nitrate/nitrite were protected in the genistein-treated group. Genistein prevented the L-NAME-induced overexpression of angiotensin II receptor type I (AT₁R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit 2 (gp91^phox), and transforming growth factor beta I (TGF-β1) in hypertensive rats. In conclusion, genistein exhibited a cardioprotective effect in hypertensive rats in this study. The molecular mechanisms might be mediated by suppression of oxidative stress through the Ang II/AT₁R/NADPH oxidase/TGF-β1 signaling pathway.

Galangin is a natural flavonoid. In this study, we evaluated whether galangin could alleviate signs of metabolic syndrome (MS) and cardiac abnormalities in rats receiving a high-fat (HF) diet. Male Sprague–Dawley rats were given an HF diet plus 15% fructose for four months, and they were fed with galangin (25 or 50 mg/kg), metformin (100 mg/kg), or a vehicle for the last four weeks. The MS rats exhibited signs of MS, hypertrophy of adipocytes, impaired liver function, and cardiac dysfunction and remodeling. These abnormalities were alleviated by galangin (p < 0.05). Interleukin-6 and tumor necrosis factor-α concentrations and expression were high in the plasma and cardiac tissue in the MS rats, and these markers were suppressed by galangin (p < 0.05). These treatments also alleviated the low levels of adiponectin and oxidative stress induced by an HF diet in rats. The downregulation of adiponectin receptor 1 (AdipoR1) and cyclooxygenase-2 (COX-2) and the upregulation of nuclear factor kappa B (NF-κB) expression were recovered in the galangin-treated groups. Metformin produced similar effects to galangin. In conclusion, galangin reduced cardiometabolic disorders in MS rats. These effects might be linked to the suppression of inflammation and oxidative stress and the restoration of AdipoR1, COX-2, and NF-κB expression.

Galangin is a polyphenolic compound found in Alpinia officinarum and propolis. This study investigated the effect of galangin on blood pressure, the renin angiotensin system (RAS), cardiac and kidney alterations and oxidative stress in two-kidney one-clipped (2K-1C) hypertensive rats. Hypertension was induced in male Sprague Dawley rats (180-220 g), and the rats were given galangin (30 and 60 mg/kg) and losartan (10 mg/kg) for 4 weeks (n = 8/group). Galangin decreased hypertension and cardiac dysfunction and hypertrophy, which was related to the reducing circulation angiotensin converting enzyme (ACE) activity and angiotensin II concentration (p < 0.05). These effects were consistent with the reduced overexpression of angiotensin II receptor type 1 (AT₁R), transforming growth factor beta 1 (TGF-β1) and collagen type I (Col I) protein in cardiac tissue (p < 0.05). Additionally, renal artery occlusion, procedure-induced kidney dysfunction and fibrosis were attenuated in the galangin-treated group. Galangin treatment normalized the overexpression of AT₁R and NADPH oxidase 4 (Nox-4) protein and normalized the downregulation of nuclear factor-erythroid Factor 2-related Factor 2 (Nrf-2) and haem oxygenase 1 (HO-1) in 2K-1C rats (p < 0.05). Galangin exhibited antioxidative effects, as it reduced systemic and tissue oxidative stress markers and increased catalase activity in 2K-1C rats (p < 0.05). In conclusion, galangin attenuated hypertension, renin-angiotensin system activation, cardiorenal damage and oxidative stress induced by renal artery stenosis in rats. These effects might be associated with modulation of the expression of AT₁R, TGF-β1 and Col I protein in the heart as well as AT₁R/Nox-4 and Nrf-2/HO-1 protein in renal tissue in hypertensive rats.

Limonin is a natural triterpenoid isolated from citrus fruit. In the present study, we examined the effects of limonin on cardiometabolic alterations in diet-induced metabolic syndrome. Metabolic syndrome was induced in rats by feeding them a high-fat (HF) diet plus 15% fructose in drinking water for 16 weeks. They were treated with limonin (50 or 100 mg/kg) (n = 8/group) for the final 4 weeks. Increases in body weight (BW), fasting blood glucose (FBG), serum insulin, total cholesterol (TC), blood pressure (BP), liver fat accumulation, and adipocyte hypertrophy, as well as oral glucose tolerance in rats with metabolic syndrome were alleviated by limonin treatment (p < 0.05). Limonin improved ejection fraction and left ventricular (LV) hypertrophy, and reduced angiotensin converting enzyme (ACE) activity and angiotensin II (Ang II) concentration in rats with metabolic syndrome (p < 0.05). It also reduced plasma tumour necrosis factor (TNF)-α, interleukin (IL)- 6, leptin, malonaldehyde (MDA), and superoxide generation, and increased catalase activity in rats with metabolic syndrome compared to controls (p < 0.05). Downregulation of insulin receptor substrate 1 (IRS-1) and glucose transporter type 4 (GLUT4) protein expression in epididymal fat pads and cardiac, liver, and gastrocnemius tissues was present in metabolic syndrome, and these were restored by limonin treatment (p < 0.05). In conclusion, limonin shows a potential effect in alleviating symptoms and improving cardiometabolic disorders. These beneficial effects are linked to the reduction of the renin-angiotensin system, inflammation, oxidative stress, and improvement of IRS-1/GLUT4 protein expression in the target tissue.