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<p>The current study aimed to evaluate the in-vitro toxicity and in-vivo antidiabetic effects of a standardized extract from <i>Eugenia uniflora</i> (<i>E. uniflora</i>) fruit, comparing its efficacy to metformin (Met), a widely used anti-hyperglycemic drug. First, toxicity of the extract was determined by MTT assay in 3T3 cell line and primary astrocyte culture. Then <i>Wistar</i> rats were divided into four groups: I- Control, II- type 2 diabetes mellitus (T2DM), III- T2DM + Met and IV- T2DM + <i>E. uniflora</i>. To induce T2DM, groups II, III and IV received a high fat diet (HFD) for 3 weeks followed by a single intraperitoneal (i.p.) dose of streptozotocin (STZ, 35&#xa0;mg/kg). Animals of group I received normal diet and vehicle (i.p.). Group III received Met (250&#xa0;mg/kg) and group IV received <i>E. uniflora</i> (200&#xa0;mg/kg) intragastric pathway, once a day, throughout all experimental protocol. Animals from the groups I and II received water in the same volume. Results showed that cell viability was not affected. In-vivo, <i>E. uniflora</i> and Met prevented the change in serum levels of glucose, cholesterol, LDL, triglyceride and interleukin-6. Furthermore, extract and Met improved oxidative stress markers and antioxidant enzyme activity in the brain (cerebral cortex, hippocampus, striatum). Furthermore, extract enhanced the downstream insulin signaling pathway, including <i>insulin receptor substrate 1</i>,<i> forkhead box protein O-3a</i>, as well as activated the <i>nuclear factor erythroid 2-related factor 2</i> in the cerebral cortex. This study indicates that <i>E. uniflora</i> extract may have potential in preventing complications associated with T2DM; nevertheless, additional studies are required to confirm these effects and establish their clinical significance.</p> Graphical Abstract <p></p>

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Protective Effects of Eugenia uniflora Red Fruit on Brain in a Rat Model of Type 2 Diabetes: Mechanistic Insights

  • 期刊论文

  • 发表日期：

    2025年10月24日

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  • Imtiaz Ahmad,
  • Juliane de Souza Cardoso,
  • Julia Eisenhardt de Mello,
  • Fernanda Cardoso Teixeira,
  • Juliane Torchelsen Saraiva,
  • Natália Pontes Bona,
  • Marcia Vizzotto,
  • Lucas Petitemberte de Souza,
  • William Borges Domingues,
  • Vinicius Farias Campos,
  • Claiton Leoneti Lencina,
  • Roselia Maria Spanevello,
  • Rejane Giacomelli Tavares,
  • Mayara Sandrielly Soares de Aguiar,
  • Francieli Moro Stefanello

摘要

The current study aimed to evaluate the in-vitro toxicity and in-vivo antidiabetic effects of a standardized extract from Eugenia uniflora (E. uniflora) fruit, comparing its efficacy to metformin (Met), a widely used anti-hyperglycemic drug. First, toxicity of the extract was determined by MTT assay in 3T3 cell line and primary astrocyte culture. Then Wistar rats were divided into four groups: I- Control, II- type 2 diabetes mellitus (T2DM), III- T2DM + Met and IV- T2DM + E. uniflora. To induce T2DM, groups II, III and IV received a high fat diet (HFD) for 3 weeks followed by a single intraperitoneal (i.p.) dose of streptozotocin (STZ, 35 mg/kg). Animals of group I received normal diet and vehicle (i.p.). Group III received Met (250 mg/kg) and group IV received E. uniflora (200 mg/kg) intragastric pathway, once a day, throughout all experimental protocol. Animals from the groups I and II received water in the same volume. Results showed that cell viability was not affected. In-vivo, E. uniflora and Met prevented the change in serum levels of glucose, cholesterol, LDL, triglyceride and interleukin-6. Furthermore, extract and Met improved oxidative stress markers and antioxidant enzyme activity in the brain (cerebral cortex, hippocampus, striatum). Furthermore, extract enhanced the downstream insulin signaling pathway, including insulin receptor substrate 1, forkhead box protein O-3a, as well as activated the nuclear factor erythroid 2-related factor 2 in the cerebral cortex. This study indicates that E. uniflora extract may have potential in preventing complications associated with T2DM; nevertheless, additional studies are required to confirm these effects and establish their clinical significance.

Graphical Abstract