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Combination Therapy of Metformin and Morin Attenuates Insulin Resistance, Inflammation, and Oxidative Stress in Skeletal Muscle of High-Fat Diet-Fed Mice Publisher Pubmed



Bahramzadeh A1 ; Samavarchi Tehrani S2 ; Goodarzi G1, 3 ; Seyyedebrahimi S1 ; Meshkani R1
Authors
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Authors Affiliations
  1. 1. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Science, Tehran, Iran
  3. 3. Department of Pathobiology and Laboratory Science, North Khorasan University of Medical Sciences, Bojnurd, Iran

Source: Phytotherapy Research Published:2024


Abstract

Lipid accumulation, inflammation, and oxidative stress are the most important causes of muscle insulin resistance. The aim of this study was to investigate the single and combined treatment effects of metformin (MET) and morin (MOR) on lipid accumulation, inflammation, and oxidative stress in the skeletal muscle of mice fed a high-fat diet. The mice were supplemented with MET (230 mg/kg diet), MOR (100 mg/kg diet), and MET + MOR for 9 weeks. Our results revealed that single treatment with MET or MOR, and with a stronger effect of MET + MOR combined treatment, reduced body weight gain, improved glucose intolerance and enhanced Akt phosphorylation in the muscle tissue. In addition, plasma and muscle triglyceride levels were decreased after treatment with MET and MOR. The expression of genes involved in macrophage infiltration and polarization and pro-inflammatory cytokines showed that MET + MOR combined treatment, significantly reduced inflammation in the muscle. Furthermore, combined treatment of MET + MOR with greater efficacy than the single treatment improved several oxidative stress markers in the muscle. Importantly, combined treatment of MET and MOR could increase the expression of nuclear factor erythroid 2–related factor 2, the master regulator of the antioxidant response. These findings suggest that combination of MET with MOR might ameliorate insulin resistance, inflammation, and oxidative stress in the skeletal muscle of mice fed high-fat diet. © 2023 John Wiley & Sons Ltd.
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