Kaempferol protects against cardiovascular abnormalities induced by nitric oxide deficiency in rats by suppressing the TNF-α pathway.

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 Nω-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-ß1) 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.

Cardiovascular complications are resolved by tuna protein hydrolysate supplementation in rats fed with a high-fat diet.

This study is aimed to investigate whether tuna protein hydrolysate (TPH) supplementation could alleviate cardiovascular complications induced by a high-fat diet (HFD) in rats. Rats were fed a HFD for 16 weeks and given TPH (100 mg/kg, 300 mg/kg, or 500 mg/kg) or metformin (100 mg/kg) (n = 8) for the last four weeks. TPH had the following effects: resolved their impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, and hypertension (p < 0.05); alleviated left ventricular dysfunction and hypertrophy (p < 0.05), and vascular dysfunction and hypertrophy (p < 0.05); adipocyte hypertrophy; increases in circulating leptin and tumor necrosis factor (TNF-α) were mitigated (p < 0.05); increased renin-angiotensin system (RAS), oxidative stress, and decreased nitric oxide metabolites were modulated (p < 0.05). TPH restored the expression of angiotensin II receptor type 1 (AT1R)/NADPH oxidase 2 (NOX2), endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1), and peroxisome proliferator-activated receptor γ (PPARγ)/the nuclear factor kappa B (NF-κB) protein in cardiovascular tissue (p < 0.05). In metabolic syndrome (MS) rats, metformin and TPH had comparable effects. In conclusion, TPH alleviated cardiovascular complications related to MS. It suppressed RAS, oxidative stress, and inflammation that were associated with modulation of AT1R/NOX2, eNOS, Nrf2/HO-1, and PPARγ/NF-κB expression.

Limonin ameliorates cardiovascular dysfunction and remodeling in hypertensive rats.

AIMS: Limonin is a tetracyclic triterpenoid isolated from citrus fruits. Here, the effects of limonin on cardiovascular abnormalities in nitric oxide-deficient rats induced by Nω-Nitrol-arginine methyl ester (L-NAME) were explored. MAIN METHODS: Male Sprague Dawley rats were given L-NAME (40 mg/kg, drinking water) for 3 weeks and then treated daily with polyethylene glycol (vehicle), limonin (50 or 100 mg/kg) or telmisartan (10 mg/kg) for two weeks. KEY FINDINGS: Limonin (100 mg/kg) markedly reduced L-NAME-induced hypertension, cardiovascular dysfunction and remodeling in rats (P < 0.05). Increases in systemic angiotensin-converting enzyme (ACE) activity and angiotensin II (Ang II) and a reduction in circulating ACE2 were restored in hypertensive rats treated with limonin (P < 0.05). Reductions in antioxidant enzymes and nitric oxide metabolites (NOx) and increases in oxidative stress components induced by L-NAME were relieved by limonin treatment (P < 0.05). Limonin suppressed the increased expression of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in cardiac tissue and circulating TNF-α in rats that received L-NAME (P < 0.05). Changes in Ang II receptor type I (AT1R), Mas receptor (MasR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) and NADPH oxidase subunit 2 (gp91phox) protein expression in cardiac and aortic tissue were normalized by limonin (P < 0.05). SIGNIFICANCE: In conclusion, limonin ameliorated L-NAME-induced hypertension, cardiovascular dysfunction and remodeling in rats. These effects were relevant to restorations of the renin-angiotensin system, oxidative stress and inflammation in NO-deficient rats. The molecular mechanisms are associated with the modulation of AT1R, MasR, NF-ĸB and gp91phox protein expression in cardiac and aortic tissue.

Mitigation effect of galangin against aortic dysfunction and hypertrophy in rats with metabolic syndrome.

Vascular alterations induced by a high-fat diet (HFD) are involved in the development of hypertension. Galangin, a flavonoid, is the major active compound isolated from galangal and propolis. The objective of this study was to investigate the effect of galangin on aortic endothelial dysfunction and hypertrophy, and the mechanisms involved in HFD-induced metabolic syndrome (MS) in rats. Male Sprague-Dawley rats (220-240 g) were separated into three groups: control + vehicle, MS + vehicle, and MS + galangin (50 mg/kg). Rats with MS received HFD plus 15% fructose solution for 16 weeks. Galangin or vehicle was orally administered daily for the final four weeks. Galangin reduced body weight and mean arterial pressure in HFD rats (p < 0.05). It also reduced circulating fasting blood glucose, insulin, and total cholesterol levels (p < 0.05). Impaired vascular responses to the exogenous acetylcholine observed in the aortic ring of HFD rats were restored by galangin (p < 0.05). However, the response to sodium nitroprusside did not differ between the groups. Galangin enhanced the expression of the aortic endothelial nitric oxide synthase (eNOS) protein and increased circulating nitric oxide (NO) levels in the MS group (p < 0.05). Aortic hypertrophy in HFD rats was alleviated by galangin (p < 0.05). Increases in tumour necrosis factor-alpha (TNF-α), interleukin (IL)-6 levels, angiotensin-converting enzyme activity and angiotensin II (Ang II) concentrations in rats with MS were suppressed in galangin treated group (p < 0.05). Furthermore, galangin reduced the upregulation of angiotensin II type I receptor (AT1R) and transforming growth factor-beta (TGF-ß) expression in rats with MS (p < 0.05). In conclusion, galangin alleviates metabolic disorders and improves aortic endothelial dysfunction and hypertrophy in the MS group. These effects were consistent with increased NO availability, reduced inflammation, and suppressing Ang II/AT1R/TGF-ß signalling pathway.

Limonin mitigates cardiometabolic complications in rats with metabolic syndrome through regulation of the IRS-1/GLUT4 signalling pathway.

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.

Hesperidin alleviates vascular dysfunction and remodelling in high-fat/high-fructose diet-fed rats by modulating oxidative stress, inflammation, AdipoR1, and eNOS expression.

Hesperidin, a flavanone glycoside, has shown antihypertensive, antioxidant, and anti-inflammatory effects. In the present study, the therapeutic effects of hesperidin on vascular function and remodelling, and possible underlying mechanisms involved in high-fat/high-fructose diet (HFFD)-fed rats were investigated. Male Sprague-Dawley rats were fed a high-fat diet plus 15% fructose in drinking water for 16 weeks. HFFD-fed rats were treated with hesperidin (30 mg/kg/day) or vehicle for the last 4 weeks. Treatment of HFFD-fed rats with hesperidin significantly attenuated metabolic alterations, vascular endothelial dysfunction and remodelling. Hesperidin markedly alleviated HFFD-induced oxidative stress and inflammation by decreasing plasma malondialdehyde level and aortic superoxide anion production, and by suppressing aortic tumor necrosis factor-α and interleukin-6 overexpression. Additionally, increased plasma levels of the adiponectin and nitric oxide metabolite, together with restoration of adiponectin receptor 1 (AdipoR1) and endothelial nitric oxide synthase (eNOS) protein expression, were also observed after treatment with hesperidin. These findings indicated that hesperidin alleviates HFFD-induced vascular dysfunction and remodelling in rats. The possible underlying mechanism may involve the reduction of oxidative stress and inflammation, and the restoration of AdipoR1and eNOS expression.

Effects of Thai native chicken breast meat consumption on serum uric acid level, biochemical parameters, and antioxidant activities in rats.

This study aimed to evaluate the effect of a high protein diet comprising breast meat from commercial broiler (BR), Thai native (PD), and commercial broiler × Thai native crossbred (KKU-ONE) chicken on serum uric acid, biochemical parameters, and antioxidant activities in rats. Male Sprague-Dawley rats were divided into four groups. The control group received a standard chow diet, and the other three groups were fed a high protein diet (70% standard diet + 30% BR, PD, or KKU-ONE chicken breast) for five weeks. The PD- and KKU-ONE-fed rats had lower plasma total cholesterol and triglyceride levels than the control rats. A decrease in HDL-c was also observed in rats fed a diet containing BR. Liver weight, liver enzyme, plasma ALP, xanthine oxidase activity, serum uric acid, creatinine, superoxide production, and plasma malondialdehyde levels increased in BR-fed rats. The findings of this study might provide evidence to support the use of Thai native and Thai native crossbred chicken breast meat as functional foods.

Cardiorenal dysfunction and hypertrophy induced by renal artery occlusion are normalized by galangin treatment in rats.

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-ß1) 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-ß1 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.

Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats.

This study investigated the effects of nobiletin on cardiorenal changes and the underlying mechanisms involved in two-kidney, one-clip (2K-1C) hypertension. 2K-1C rats were treated with nobiletin (15 or 30 mg/kg/day) or losartan (10 mg/kg/day) for 4 weeks (n = 8/group). Nobiletin (30 mg/kg) reduced high levels of blood pressure and circulating angiotensin II and angiotensin-converting enzyme activity in 2K-1C rats. Left ventricular (LV) dysfunction and remodelling in 2K-1C rats were alleviated in the nobiletin-treated group (P < 0.05). Nobiletin reduced the upregulation of Ang II type I receptor (AT1R)/JAK (Janus kinase)/STAT (signal transducer and activator of transcription) protein expression in cardiac tissue of 2K-1C rats (P < 0.05). The reduction in kidney function, and accumulation of renal fibrosis in 2K-1C rats were alleviated by nobiletin (P < 0.05). Overexpression of AT1R and NADPH oxidase 4 (Nox4) protein in nonclipped kidney tissue was suppressed in the nobiletin-treated group (P < 0.05). The elevations in oxidative stress parameters and the reductions in antioxidant enzymes were attenuated in 2K-1C rats treated with nobiletin (P < 0.05). In summary, nobiletin had renin-angiotensin system inhibitory and antioxidant effects and attenuated LV dysfunction and remodelling via restoration of the AT1R/JAK/STAT pathway. Nobiletin also resolved renal damage that was related to modulation of the AT1R/Nox4 cascade in 2K-1C hypertension.

Genistein alleviates renin-angiotensin system mediated vascular and kidney alterations in renovascular hypertensive rats.

Genistein is a bioflavonoid mainly found in soybean. This study evaluated the effect of genistein on vascular dysfunction and kidney damage in two-kidney, one-clipped (2K1C) hypertensive rats. Male Sprague-Dawley-2K1C hypertensive rats were treated with genistein (40 or 80 mg/kg) or losartan 10 mg/kg (n = 8/group). Genistein reduced blood pressure, attenuated the increase in sympathetic nerve-mediated contractile response and endothelial dysfunction in the mesenteric vascular beds and aorta of 2K1C rats. Increases in the intensity of tyrosine hydroxylase (TH) in the mesentery and plasma norepinephrine (NE) were alleviated in the genistein-treated group. Genistein also improved renal dysfunction, hypertrophy of the non-clipped kidney (NCK) and atrophy of the clipped kidney (CK) in 2K1C rats. Upregulation of angiotensin II receptor type I (AT1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit 4 (Nox4) and Bcl2-associated X protein (BAX) and downregulation of B-cell lymphoma 2 (Bcl2) protein found in CK were restored by genistein. It also suppressed the overexpression of AT1R, transforming growth factor beta I (TGF-ß1), smad2/3 and p-smad3 in NCK. Genistein reduced serum angiotensin converting enzyme (ACE) activity and plasma angiotensin II (Ang II) in 2K1C rats. Low levels of catalase activity as well as high levels of superoxide generation and malondialdehyde (MDA) in 2K1C rats were restored by genistein treatment. In conclusion, genistein suppressed renin-angiotensin system-mediated sympathetic activation and oxidative stress in 2K1C rats. It alleviated renal atrophy in CK via modulation of AT1R/NADPH oxidase/Bcl-2/BAX pathways and hypertrophy in NCK via AT1R/TGF-ß1/smad-dependent signalling pathways.

Imperatorin attenuates cardiac remodelling and dysfunction in high-fat/high-fructose diet-fed rats by modulating oxidative stress, inflammation, and Nrf-2 expression.

Imperatorin, an active natural furocoumarin, exerts a wide range of biological activities. In the present study, the therapeutic effects of imperatorin on cardiac function and remodelling and the possible underlying mechanisms involved in high-fat/high-fructose diet (HFFD)-fed rats were investigated. Male Sprague-Dawley rats were fed a high-fat diet plus 15 % fructose in drinking water for 16 weeks. HFFD-fed rats were treated with imperatorin (15 or 30 mg/kg/day) for the last 4 weeks. Treatment of HFFD-fed rats with imperatorin significantly reduced dyslipidaemia, hyperinsulinaemia, and hypertension. Imperatorin markedly alleviated HFFD-induced cardiac morphology alterations and left ventricular (LV) dysfunction. Imperatorin also significantly decreased malondialdehyde concentration and increased catalase activity in plasma and cardiac tissue. Additionally, decreased plasma tumour necrosis factor-α and interleukin-6 concentrations, together with restoration of cardiac nuclear factor-erythroid 2-related factor 2 (Nrf-2) protein expression, were also observed after treatment with imperatorin. These findings indicated that imperatorin alleviates HFFD-induced cardiac remodelling and LV dysfunction in rats. The possible underlying mechanism may involve the reduction of oxidative stress and inflammation, and the restoration of Nrf-2 expression.

Clitoria ternatea (Linn.) flower extract attenuates vascular dysfunction and cardiac hypertrophy via modulation of Ang II/AT1 R/TGF-ß1 cascade in hypertensive rats.

BACKGROUND: Clitoria ternatea (CT) (the Fabaceae family) has been reported to elicit several biological responses, such as anti-inflammation and anti-depression effects. This study evaluated the effect of CT flower extract on blood pressure, vascular function, and left ventricular hypertrophy in a two-kidney, one-clip (2K-1C) rat model. Hypertensive rats were treated with CT extract at various doses (100, 300, or 500 mg kg-1 day-1 ) or losartan (10 mg kg-1 day-1 ) for 4 weeks (n = 8/group). RESULTS: CT extract reduced blood pressure in a dose-dependent manner, and CT extract at a dose of 300 mg kg-1 was an effective concentration (P < 0.05). Augmentation of contractile responses to electrical field stimulation and impairment of vascular responses to acetylcholine in mesenteric vascular beds and aortic rings of 2K-1C rats were suppressed by treatment with CT extract or losartan (P < 0.05). Serum angiotensin-converting enzyme activity and plasma angiotensin II concentration were high in 2K-1C rats but alleviated by CT extract or losartan treatment (P < 0.05). Increases in superoxide production and lipid peroxidation were attenuated in 2K-1C rats treated with CT extract or losartan compared with the untreated group (P < 0.05). Increased plasma concentration of nitric oxide metabolites was found in hypertensive rats that received CT extract or losartan. CT extract or losartan suppressed the overexpression of Ang II receptor subtype I (AT1 -R) and transforming growth factor-ß1 (TGF-ß1) in 2K-1C rats. CONCLUSION: CT extract had antihypertensive effects that were associated with improving vascular function and cardiac hypertrophy in 2K-1C rats. The mechanisms involved suppression of the renin-angiotensin system, of oxidative stress, and of the AT1 R/TGF-ß1 cascade. © 2021 Society of Chemical Industry.

Galangin alleviates vascular dysfunction and remodelling through modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats.

Galangin is a natural flavonoid isolated from ginger, honey and propolis. AIMS: To investigate the effect of galangin on blood pressure, vascular changes, sympathoexcitation, oxidative stress and inflammation in rats treated with NG-nitro-l-arginine methyl ester (l-NAME). MATERIALS AND METHODS: Male Wistar rats (220-250 g) were given l-NAME (0.5 mg/mL in drinking water) to induce hypertension for 5 weeks. They were treated with vehicle, galangin (30 or 60 mg/kg), or amlodipine (10 mg/kg) for the final two weeks (n = 6/group). KEY FINDINGS: Galangin significantly reduced blood pressure and improved the impairment of endothelium-dependent vasodilation in hypertensive rats. Sympathoexcitation, including enhancement of contractile responses to electrical field stimulation, increases in intensity of tyrosine hydroxylase and plasma norepinephrine concentration in hypertensive rats, was attenuated by galangin treatment. Galangin also reduced systemic and vascular oxidative damage and increased plasma nitric oxide levels in the hypertensive groups. Aortic remodelling accompanied by aortic wall hypertrophy and fibrosis observed in hypertensive rats were alleviated by galangin treatment. Furthermore, galangin exhibited an anti-inflammatory effect by suppressing the upregulation of tumour necrosis factor receptor 1 (TNF-R1), phospho-nuclear factor kappa B (p-NF-κB) and vascular cell adhesion protein 1 (VCAM-1) in aortic tissue and reducing plasma tumour necrosis factor alpha (TNF-α) in l-NAME rats. In conclusion, galangin had antihypertensive effects that were relevant to attenuating endothelial dysfunction, sympathoexcitation and vascular remodelling. These effects might be contributed by antioxidant and anti-inflammatory capacities and modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats.

Diosmetin Ameliorates Vascular Dysfunction and Remodeling by Modulation of Nrf2/HO-1 and p-JNK/p-NF-κB Expression in Hypertensive Rats.

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 anti-inflammatory 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.

Galangin Resolves Cardiometabolic Disorders through Modulation of AdipoR1, COX-2, and NF-κB Expression in Rats Fed a High-Fat Diet.

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.

Clitoria ternatea L. extract prevents kidney damage by suppressing the Ang II/Nox4/oxidative stress cascade in l-NAME-induced hypertension model of rats.

Clitoria ternatia L. (CT) has been reported to have anti-inflammatory and antioxidant effects. This study investigated the effect of CT aqueous flower extract on blood pressure and renal alterations in Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced hypertensive rats. Male Sprague Dawley rats received l-NAME in drinking water and were treated with CT flower extract or lisinopril. CT aqueous flower extract and lisinopril alleviated l-NAME-induced hypertension (p < 0.05). Glomerular extracellular matrix accumulation, renal fibrosis, and increased serum creatinine levels were observed in l-NAME-induced hypertensive rats and attenuated by CT flower extract or lisinopril co-treatment (p < 0.05). High levels of plasma angiotensin II (Ang II) and upregulated nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) protein expression in the kidneys induced by l-NAME were alleviated by CT flower extract or lisinopril co-treatment (p < 0.05). Furthermore, CT flower extract and lisinopril treatment reduced lipid peroxidation and elevated plasma and kidney malondialdehyde levels in l-NAME-induced hypertensive rats (p < 0.05). In conclusion, CT flower extract prevented l-NAME-induced renal injury and dysfunction in rats. The possible mechanism may be related to the suppression of Ang II-mediated Nox4 expression and the oxidative stress cascade in rats.

Butterfly Pea Flower (Clitoria ternatea Linn.) Extract Ameliorates Cardiovascular Dysfunction and Oxidative Stress in Nitric Oxide-Deficient Hypertensive Rats.

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.

Imperatorin alleviates metabolic and vascular alterations in high-fat/high-fructose diet-fed rats by modulating adiponectin receptor 1, eNOS, and p47phox expression.

In the present study, the therapeutic effects of imperatorin on metabolic and vascular alterations and possible underlying mechanisms were investigated in high-fat/high-fructose diet (HFFD)-fed rats. Male Sprague-Dawley rats were fed a high-fat diet plus 15% fructose in drinking water for 16 weeks. HFFD-fed rats were treated with imperatorin (15 or 30 mg/kg/day) for the last 4 weeks. In HFFD-fed rats, imperatorin significantly reduced obesity, hypertension, dyslipidemia, and insulin resistance. Imperatorin markedly improved vascular endothelial function and alleviated changes in vascular morphology. Furthermore, imperatorin treatment significantly increased the plasma levels of the nitric oxide metabolite and adiponectin, and upregulated adiponectin receptor 1 and endothelial nitric oxide synthase (eNOS) protein expression in the thoracic aorta. Imperatorin treatment decreased vascular superoxide anion production and downregulated aortic NADPH oxidase subunit p47phox protein expression. These findings indicated that imperatorin alleviates HFFD-induced metabolic and vascular alterations in rats. The possible underlying mechanism may involve the restoration of adiponectin receptor 1 and eNOS expression and suppression of p47phox expression.

Genistein Prevents Nitric Oxide Deficiency-Induced Cardiac Dysfunction and Remodeling in Rats.

Genistein is an isoflavone found in soybeans. This study evaluates the protective effects of genistein on Nω-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 (gp91phox), and transforming growth factor beta I (TGF-ß1) 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-ß1 signaling pathway.

Diosmetin attenuates metabolic syndrome and left ventricular alterations via the suppression of angiotensin II/AT1 receptor/gp91phox/p-NF-κB protein expression in high-fat diet fed rats.

Diosmetin, a monomethoxyflavone, is isolated from citrus fruits. The objective of this research was to test the biological role of diosmetin on parameters of metabolic syndrome (MS) and left ventricular (LV) alterations in rats fed with a high-fat (HF) diet. MS was induced by feeding male Sprague-Dawley rats with a HF diet plus 15% fructose in drinking water for 16 weeks. MS rats were given diosmetin (20 or 40 mg per kg per day) or metformin (100 mg per kg per day) for the final four weeks. Diosmetin attenuated signs of MS including, hypertension, hyperglycemia, insulin resistance, and dyslipidemia in rats that received the HF diet (p < 0.05). A decreased stroke volume, ejection fraction, fractional shortening, LV hypertrophy and fibrosis present in the MS group were alleviated by diosmetin treatment (p < 0.05). Diosmetin also suppressed angiotensin-converting enzyme activity, plasma angiotensin II (Ang II) levels and angiotensin II type 1 (AT1) receptor protein expression in MS rats. Increases in superoxide (O2˙-) formation, plasma malondialdehyde, plasma nitrate and nitrite and gp91phox expression induced by a HF diet were ameliorated in the diosmetin treated group. Inflammation indicated by an increased phospho nuclear factor kappa B (p-NF-κB) protein expression and cardiac TNF-α concentration was reduced in MS rats receiving diosmetin (p < 0.05). Metformin also attenuated MS, cardiac abnormalities relevant to decreasing the renin-angiotensin system stimulation, reactive oxygen species and inflammation in MS rats (p < 0.05). Diosmetin alleviated MS and LV dysfunction and remodeling in HF diet-induced MS rats. These results could be associated with the suppression of the Ang II/AT1 receptor/gp91phox/p-NF-κB protein pathway.