Melanoxetin: A Hydroxylated Flavonoid Attenuates Oxidative Stress and Modulates Insulin Resistance and Glycation Pathways in an Animal Model of Type 2 Diabetes <i>Mellitus</i>
Sónia Rocha,
Andreia Amaro,
Marcos D. Ferreira-Junior,
Carina Proença,
Artur M. S. Silva,
Vera M. Costa,
Sara Oliveira,
Diogo A. Fonseca,
Sónia Silva,
Maria Luísa Corvo,
Marisa Freitas,
Paulo Matafome,
Eduarda Fernandes
Affiliations
Sónia Rocha
Associated Laboratory for Green Chemistry (LAQV), Network of Chemistry and Technology (REQUIMTE), Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Andreia Amaro
Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
Marcos D. Ferreira-Junior
Department of Physiological Sciences, Institute of Biological Sciences, University Federal of Goiás, Goiânia 74690-900, Brazil
Carina Proença
Associated Laboratory for Green Chemistry (LAQV), Network of Chemistry and Technology (REQUIMTE), Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Artur M. S. Silva
LAQV, REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Vera M. Costa
Research Unit on Applied Molecular Biosciences (UCIBIO), Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Sara Oliveira
Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
Diogo A. Fonseca
Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
Sónia Silva
Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
Maria Luísa Corvo
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal
Marisa Freitas
Associated Laboratory for Green Chemistry (LAQV), Network of Chemistry and Technology (REQUIMTE), Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Paulo Matafome
Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
Eduarda Fernandes
Associated Laboratory for Green Chemistry (LAQV), Network of Chemistry and Technology (REQUIMTE), Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin’s therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.
