Bixin Combined with Metformin Ameliorates Insulin Resistance and Antioxidant Defenses in Obese Mice

Author:

Pinheiro Camila Graça1,Motta Bruno Pereira1,Oliveira Juliana Oriel1,Cardoso Felipe Nunes1,Figueiredo Ingrid Delbone1,Machado Rachel Temperani Amaral2,da Silva Patrícia Bento2,Chorilli Marlus2ORCID,Brunetti Iguatemy Lourenço1,Baviera Amanda Martins1ORCID

Affiliation:

1. Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, Brazil

2. Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, Brazil

Abstract

Bixin (C25H30O4; 394.51 g/mol) is the main apocarotenoid found in annatto seeds. It has a 25-carbon open chain structure with a methyl ester group and carboxylic acid. Bixin increases the expression of antioxidant enzymes, which may be interesting for counteracting oxidative stress. This study investigated whether bixin-rich annatto extract combined with metformin was able to improve the disturbances observed in high-fat diet (HFD)-induced obesity in mice, with an emphasis on markers of oxidative damage and antioxidant defenses. HFD-fed mice were treated for 8 weeks with metformin (50 mg/kg) plus bixin-rich annatto extract (5.5 and 11 mg/kg). This study assessed glucose tolerance, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma, fluorescent AGEs (advanced glycation end products), TBARSs (thiobarbituric acid-reactive substances), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver and kidneys. Treatment with bixin plus metformin decreased body weight gain, improved insulin sensitivity, and decreased AGEs and TBARSs in the plasma, liver, and kidneys. Bixin plus metformin increased the activities of PON-1, SOD, CAT, and GSH-Px. Bixin combined with metformin improved the endogenous antioxidant defenses in the obese mice, showing that this combined therapy may have the potential to contrast the metabolic complications resulting from oxidative stress.

Funder

Fundação de Amparo a Pesquisa do Estado de São Paulo

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

MDPI AG

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