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

Abstract

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.

Keywords: adiponectin; cardiac function; galangin; inflammation; metabolic syndrome; oxidative stress.

Figure 1

Effects of galangin and metformin treatments on blood glucose concentrations: (A) oral glucose tolerance test (OGTT) and (B) and area under the curve (AUC) of OGTT. Data are presented as the mean ± S.E.M. (n = 8). ^a p < 0.05 vs. the control group, ^b p < 0.05 vs. the MS group, and ^c p < 0.05 vs. MS + the galangin (25 mg/kg) group.

Figure 2

Morphology of epididymal fat pads. (A) Representative photographs of epididymal fat sections stained with hematoxylin and eosin (H&E) (magnification ×200, scale bar = 50 µm). (B) Effects of galangin and metformin treatments on adipocyte cell areas. Data are presented as the mean ± S.E.M. (n = 8). ^a p < 0.05 vs. the control group, ^b p < 0.05 vs. the MS group, ^c p < 0.05 vs. the MS + galangin (25 mg/kg) group, and ^d p < 0.05 vs. the MS + galangin (50 mg/kg) group.

Figure 3

Effects of galangin and metformin treatments on systolic blood pressure. Data are presented as the mean ± S.E.M. (n = 8). ^a p < 0.05 vs. the control group, ^b p < 0.05 vs. the MS group, ^c p < 0.05 vs. the MS + galangin (25 mg/kg) group, and ^d p < 0.05 vs. the MS + galangin (50 mg/kg) group.

Figure 4

Morphology of heart. (A) Representative photographs of heart sections stained with H&E (magnification ×10) (scale bar = 5 mm). (B) Representative cross-sections of cardiomyocytes stained with H&E (magnification ×400) (scale bar = 20 µm). (C) Effects of galangin and metformin treatments on left ventricular wall thickness, (D) cross-sectional areas, (E) left ventricular luminal areas, (F) wall/lumen ratio, and (G) cardiomyocyte area. Results are shown as the mean ± S.E.M. (n = 8). ^a p < 0.05 vs. the control group, ^b p < 0.05 vs. the MS group, ^c p < 0.05 vs. the MS + galangin (25 mg/kg) group, and ^d p < 0.05 vs. the MS + galangin (50 mg/kg) group.

Figure 5

Effects of galangin and metformin treatments on tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) immunohistochemical staining for myocardial and TNF-α and IL-6 levels. (A) TNF-α, (B) IL-6 (Brown Chromogen) immunohistochemical staining in myocardia (magnification × 400) (scale bar = 10 µm), (C) relative TNF-α-stained area (%), (D) relative IL-6-stained area (%), (E) plasma TNF-α, and (F) plasma IL-6. Results are shown as the mean ± S.E.M. (n = 8). ^a p < 0.05 vs. the control group, ^b p < 0.05 vs. the MS group, and ^c p < 0.05 vs. the MS + galangin (25 mg/kg) group.

Figure 6

Effects of galangin and metformin treatments on plasma adiponectin levels. Results are shown as the mean ± S.E.M. (n = 8). ^a p < 0.05 vs. the control group and ^b p < 0.05 vs. the MS group.

Figure 7

Effects of galangin and metformin treatments on oxidative stress markers and endogenous antioxidant enzymes. (A) Aortic superoxide production, (B) plasma malondialdehyde (MDA) level, (C) heart MDA level (D) plasma superoxide dismutase (SOD) activity, (E) plasma catalase (CAT) activity, and (F) heart CAT activity. Results are shown as the mean ± S.E.M. (n = 8). ^a p < 0.05 vs. the control group, ^b p < 0.05 vs. the MS group, and ^c p < 0.05 vs. the MS + galangin (25 mL/kg) group.

Figure 8

Effects of galangin and metformin treatments on protein expression in heart: (A) AdipoR1, (B) COX-2, and (C) p-NF-κB. Data are presented as the mean ± S.E.M. (n = 3–4). ^a p < 0.05 vs. the control group and ^b p < 0.05 vs. the MS group. ^c p < 0.05 vs. MS + Galangin (25 mL/kg) group. AdipoR1: adiponectin receptor 1; COX-2: cyclooxygenase-2; p-NF-κB: phospho-nuclear factor kappa B.