Impacts of the combined therapy between curcumin and metformin on markers of glycoxidative stress in in vivo and in vitro model systems of metabolic dysfunctions

• Grant number: 24/20946-0
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Amanda Martins Baviera
• Grantee: Amanda Martins Baviera
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• City of the host institution: Araraquara
• Associated researchers: Ana Marisa Fusco Almeida ; Iguatemy Lourenço Brunetti ; NAJEH MAISSAR KHALIL

Abstract

Various pathogenic events contribute to the development of complications observed in diabetes mellitus (DM) and obesity, including glycoxidative stress. Chronic hyperglycemia results in an increased generation of reactive oxygen species (ROS) that exceeds the capacity of antioxidant defenses, resulting in functional impairments of biomolecules through dicarbonyl stress in proteins and lipid peroxidation in biological membranes. Hyperglycemia also contributes to the exacerbated generation of advanced glycation end products (AGEs). AGEs lead to impaired protein function via crosslinking; they also interact with cellular AGE receptors (RAGE), increasing the activation of pro-inflammatory pathways and the formation of ROS. Metformin has been widely used in the treatment of T2DM and insulin resistant states. In addition to achieving the effective glycemic control, strategies of combined therapies between antidiabetic drugs and natural bioactives with antioxidant and antiglycation activities have been suggested, in an attempt to reduce the long-term deleterious impacts of reactive species and advanced glycation events, mitigating the diabetic complications. Curcumin is a polyphenol obtained from the rhizomes of Curcuma longa. Literature is wide on the biological activities of curcumin, including its benefits in the metabolic disorders. The low bioavailability of curcumin can be overcome with oral formulation strategies, and in the present study its delivery in a nanostructured lipid carrier will be used. The aim of this study is to evaluate the effects of the combined therapy with curcumin and metformin on physiometabolic parameters, markers of glycoxidative stress, antioxidant defenses and components of AGE detoxification machinery, in an experimental model of obesity, as well as the effects of this combined therapy on the viability and function of human neutrophils as representatives of the immune system and on a liver-on-a-chip platform with hepatic spheroids under an insulin resistance model. The results obtained within the scope of this project will contribute to the development of innovative therapeutic strategies in the management of complications observed in DM and obesity. (AU)