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<p>In 2022, World Health Organization (WHO) established global objectives for diabetes, aiming for 80% of people with diabetes to achieve good control of glycaemia and blood pressure by 2030. Currently, there are approximately 537 million adults living with diabetes, placing them at a high risk of developing various complications. Discovering new antidiabetic agents involves exploring leading compounds with therapeutic activity and optimizing their structure in medicinal chemistry research. Phenolic compounds, derived from plant metabolism, are widely distributed in nature and known for their diverse biological properties, including antidiabetic activity. Over the past decade, carbohydrate response element-binding protein (ChREBP), consisting of α and β subunits, has been identified as a central mediator of glucose sensing in multiple metabolic organs. Nuclear factor erythroid 2-related factor 2 (NRF2) is a significant transcription factor involved in cellular stress resistance and represents a logical target for exogenous activators to combat chronic metabolic disorders. Recent findings reveal that NRF2 activation is necessary for ChREBPα-mediated enhancement of glucose-stimulated β-cell proliferation. This review aims to describe the modulatory effect of phenolic compounds on ChREBP and NRF2, focusing on their potential for type 2 diabetes treatment. It assesses relevant in vitro, in vivo, and human studies conducted over the past 10&#xa0;years. Several analyzed compounds show promising activity and may be utilized in future diabetes therapy.</p>

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Evidence of phenolic compounds as modulators of ChREBP and NRF2 in type 2 diabetes: a review of their potential for drug development

  • 期刊论文

  • 发表日期：

    2025年3月6日

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  • Carina Proença,
  • Maria Carolina Lobo,
  • Ana T. Rufino,
  • José Miguel P. Ferreira de Oliveira,
  • Marisa Freitas,
  • Jenifer Trepiana,
  • María P. Portillo,
  • Félix Carvalho,
  • Eduarda Fernandes

摘要

In 2022, World Health Organization (WHO) established global objectives for diabetes, aiming for 80% of people with diabetes to achieve good control of glycaemia and blood pressure by 2030. Currently, there are approximately 537 million adults living with diabetes, placing them at a high risk of developing various complications. Discovering new antidiabetic agents involves exploring leading compounds with therapeutic activity and optimizing their structure in medicinal chemistry research. Phenolic compounds, derived from plant metabolism, are widely distributed in nature and known for their diverse biological properties, including antidiabetic activity. Over the past decade, carbohydrate response element-binding protein (ChREBP), consisting of α and β subunits, has been identified as a central mediator of glucose sensing in multiple metabolic organs. Nuclear factor erythroid 2-related factor 2 (NRF2) is a significant transcription factor involved in cellular stress resistance and represents a logical target for exogenous activators to combat chronic metabolic disorders. Recent findings reveal that NRF2 activation is necessary for ChREBPα-mediated enhancement of glucose-stimulated β-cell proliferation. This review aims to describe the modulatory effect of phenolic compounds on ChREBP and NRF2, focusing on their potential for type 2 diabetes treatment. It assesses relevant in vitro, in vivo, and human studies conducted over the past 10 years. Several analyzed compounds show promising activity and may be utilized in future diabetes therapy.