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.

Effects of diosmetin on signs of metabolic syndrome and cardiac alterations in high-fat diet fed rats.

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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.

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‐β1 (TGF‐β1) 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 AT1R/TGF‐β1 cascade. © 2021 Society of Chemical Industry.

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Background: Rats fed with a high-fat diet exerts signs of cardiometabolic disorders. Galangin is a natural flavonoid mainly isolated from honey and Alpinia officinarum Hance and has various biological activities. This study evaluated whether galangin could alleviate cardiometabolic disorders, inflammation and oxidative stress in a high-fat diet fed rats. Methods: Male Sprague-Dawley rats were fed with a high-fat diet plus 15% fructose in drinking water for 4 months to induced signs of metabolic syndrome (MS), and they were treated with galangin at a dose 25 or 50 mg/kg or metformin at a dose 100 mg/kg or vehicle for the last four weeks. All data were expressed as mean ± S.E.M. Data were analyzed by one-way analysis of variance followed by Tukey’s post-hoc test for multiple comparisons analysis.Results: Rats fed with a high-fat diet had impaired glucose tolerance, insulin resistance, hyperglycemia, hypertrophy of adipocytes, impaired liver function and hypertension. These signs of MS were alleviated by galangin or metformin treatment (p<0.05). Galangin or metformin alleviated cardiac dysfunction and remodeling induced by a high-fat diet in rats (p<0.05). Tumor necrosis factor-α and interleukin-6 concentrations and expression were high in plasma and cardiac tissue in MS rats, and these inflammatory markers were suppressed by galangin or metformin treatment (p<0.05). Galangin alleviated a high-fat diet induced low levels of adiponectin in rats. Galangin or metformin decreased oxidative stress biomarkers, aortic superoxide generation and plasma and cardiac MDA levels, and raised endogenous antioxidant enzume activities, catalase, and superoxide dismutase, in MS rats (p<0.05). Downregulation of adiponectin receptor1 (AdipoR1) and cyclooxygenase-2 (COX-2) as well as upregulation of nuclear factor kappa B (NF-κB) expression were observed in MS rats. These alterations of protein expressions were recovered in MS rats treated with galangin or metformin. Conclusions: Galangin reduced cardiometabolic disorders in high-fat diet induced MS rats. The underlying mechanisms might be relevant to suppression of inflammation and oxidative stress and restoration of AdipoR1/COX-2/NF-κB expression.

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