Korean J Physiol Pharmacol.  2021 May;25(3):177-187. 10.4196/kjpp.2021.25.3.177.

Morin alleviates fructose-induced metabolic syndrome in rats via ameliorating oxidative stress, inflammatory and fibrotic markers

• Heeba GH
• Rabie EM
• Abuzeid MM
• Bekhit AA
• Khalifa MM

• KMID: 2514943
• DOI: http://doi.org/10.4196/kjpp.2021.25.3.177

Abstract

Metabolic syndrome (MBS) is a widespread disease that has strongly related to unhealthy diet and low physical activity, which initiate more serious conditions such as obesity, cardiovascular diseases and type 2 diabetes mellitus. This study aimed to examine the therapeutic effects of morin, as one of the flavonoids constituents, which widely exists in many herbs and fruits, against some metabolic and hepatic manifestations observed in MBS rats and the feasible related mechanisms. MBS was induced in rats by high fructose diet feeding for 12 weeks. Morin (30 mg/ kg) was administered orally to both normal and MBS rats for 4 weeks. Liver tissues were used for determination of liver index, hepatic expression of glucose transporter 2 (GLUT2) as well as both inflammatory and fibrotic markers. The fat/muscle ratio, metabolic parameters, systolic blood pressure, and oxidative stress markers were also determined. Our data confirmed that the administration of morin in fructose diet rats significantly reduced the elevated systolic blood pressure. The altered levels of metabolic parameters such as blood glucose, serum insulin, serum lipid profile, and oxidative stress markers were also reversed approximately to the normal values. In addition, morin treatment decreased liver index, serum liver enzyme activities, and fat/muscle ratio. Furthermore, morin relatively up-regulated GLUT2 expression, however, down-regulated NF-kB, TNF-β, and TGF-β expressions in the hepatic tissues. Here, we revealed that morin has an exquisite effect against metabolic disorders in the experimental model through, at least in part, antioxidant, anti-inflammatory, and anti-fibrotic mechanisms.

Keyword

Flavonoids; Fructose; Insulin resistance; Liver; Metabolic syndrome

Figure

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  Fig. 1 Effect of morin on OGTT (A) and AUC of OGTT (B) in fructose-fed rats. Values are presented as mean ± SEM (n = 8 rats). OGTT, oral glucose tolerance test; AUC, area under the curve; FRC, fructose; MOR, morin; MBS, metabolic syndrome. *,#Significantly different from normal control and MBS groups, respectively at p < 0.05.

• 

  Fig. 2 Effect of morin on systolic blood pressure in MBS rats. Values are presented as mean ± SEM (n = 8 rats). FRC, fructose; MOR, morin; MBS, metabolic syndrome. *,#Statistically significant from normal control and FRC groups, respectively at p < 0.05 at each time point (week) by using two-way analysis of variance (ANOVA) followed by Bonferroni post analysis test.

• 

  Fig. 3 Effect of morin on GLUT2 and NF-κB mRNA expressions in fructose-fed rat’s liver. Data are reported as: (A) representative electrophoretic analysis of RT-PCR products; (B) and (C) graphs present the ratio of densitometric measurements (optical density, OD) of samples to the corresponding reporter gene (β-actin). Values are presented as mean ± SEM (n = 8 rats). GLUT2, glucose transporter 2; NF-κB, nuclear factor-kappa B; FRC, fructose; MOR, morin; MBS, metabolic syndrome. *,#Statistically significant compared with normal control and MBS groups, respectively at p < 0.05.

• 

  Fig. 4 Effect of morin on TNF-α and TGF-β protein expressions in MBS rats. Data are reported as: (A) representative electrophoretic analysis of Western blotting products; (B) and (C) graphs present the ratio of densitometric measurements (optical density, OD) of samples to the corresponding reporter gene (β-actin). Representative Western blots and the bar graph show analysis of four separate experiments (n = 4 rats). TNF-α, tumor necrosis factor-α; TGF-β, transforming growth factor-β; FRC, fructose; MOR, morin; MBS, metabolic syndrome. *,#Statistically significant compared with normal control and MBS groups, respectively at p < 0.05.

• 

  Fig. 5 Light microscopic examination of liver sections of normal control (A) and control morin (B) groups showing no histopathological alteration and normal histological structure of the central vein (cv) and surrounding hepatocytes (h) (H&E x40). Hepatic section of MBS group (C1) shows fatty changes (f) in a diffuse manner all over the hepatocytes (arrow) associated with inflammatory cells infiltration in between and few fibrosis in the portal area (pa) (arrow head) (H&E x40); (C2) magnification of the same section at x80. Hepatic section of morin-treated group (D1) showing few inflammatory cells infiltration in the portal are associated with fatty change (arrow) in some of the hepatocytes and congestion in the central vein and sinusoids (H&E x40); (D2) magnification of the same section at x80.

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