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<p>Widely recognized for its translational relevance, the zebrafish (<i>Danio rerio</i>) is a validated model for evaluating antihyperglycemic agents. Nanocapsulation technologies have been proposed to enhance the bioefficacy of natural compounds such as curcumin (CUR), a bioactive compound derived from the turmeric plant (<i>Curcuma longa</i>) known for its anti-inflammatory and antioxidant properties. This study evaluated the effects of dietary curcumin, nano-formulated curcumin, and metformin, an oral antihyperglycemic medication commonly used to manage type 2 diabetes mellitus, on glycemic control, hepatic enzymatic activity, transcriptional levels of insulin a (<i>insa</i>) and phosphoenolpyruvate carboxykinase (<i>pck</i>), as well as intestinal and branchial histopathology in hyperglycemic adult zebrafish. Hyperglycemia was induced using dextrose monohydrate concurrently with the initiation of dietary interventions. Hyperglycemic fish were allocated to five groups receiving either an additive-free diet (Control + G), metformin (Met), curcumin (400&#xa0;mg/kg; CUR400), or curcumin encapsulated in nanoscale zeolitic imidazolate framework-8 (ZIF-8) at 200 or 400&#xa0;mg/kg (ZIFCUR200, ZIFCUR400) for 24 days. Non-hyperglycemic fish fed a standard diet served as negative controls (Control − G). Dietary curcumin at 400&#xa0;mg/kg significantly improved glycemic control, modulated hepatic enzymatic activity, and downregulated <i>pck</i> expression in hyperglycemic zebrafish, while attenuating intestinal and branchial histopathological alterations compared with Control + G and ZIF-8-treated groups (<i>p</i> &lt; 0.05). These effects were comparable to those observed with metformin as an anti-hyperglycemia drug. In contrast, nano-formulation of curcumin via ZIF-8 did not enhance its efficacy in glycemic regulation, <i>insa</i> expression, or tissue protection. Overall, curcumin demonstrated potential as a bioactive agent for mitigating hyperglycemia-induced physiological disturbances, underscoring its therapeutic applicability.</p>

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Evaluation of anti-hyperglycemic, hepatic gene-modulatory and tissue-protective effects of curcumin, curcumin-loaded zeolitic imidazolate framework-8, and metformin in zebrafish (Danio rerio)

  • 期刊论文

  • 发表日期：

    2026年5月26日

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  • Houriyeh Moghadam,
  • Iman Sourinejad,
  • Mohammad Reza Kalbassi,
  • Mohammad Behzadi Tayemeh,
  • Seyed Ali Johari

摘要

Widely recognized for its translational relevance, the zebrafish (Danio rerio) is a validated model for evaluating antihyperglycemic agents. Nanocapsulation technologies have been proposed to enhance the bioefficacy of natural compounds such as curcumin (CUR), a bioactive compound derived from the turmeric plant (Curcuma longa) known for its anti-inflammatory and antioxidant properties. This study evaluated the effects of dietary curcumin, nano-formulated curcumin, and metformin, an oral antihyperglycemic medication commonly used to manage type 2 diabetes mellitus, on glycemic control, hepatic enzymatic activity, transcriptional levels of insulin a (insa) and phosphoenolpyruvate carboxykinase (pck), as well as intestinal and branchial histopathology in hyperglycemic adult zebrafish. Hyperglycemia was induced using dextrose monohydrate concurrently with the initiation of dietary interventions. Hyperglycemic fish were allocated to five groups receiving either an additive-free diet (Control + G), metformin (Met), curcumin (400 mg/kg; CUR400), or curcumin encapsulated in nanoscale zeolitic imidazolate framework-8 (ZIF-8) at 200 or 400 mg/kg (ZIFCUR200, ZIFCUR400) for 24 days. Non-hyperglycemic fish fed a standard diet served as negative controls (Control − G). Dietary curcumin at 400 mg/kg significantly improved glycemic control, modulated hepatic enzymatic activity, and downregulated pck expression in hyperglycemic zebrafish, while attenuating intestinal and branchial histopathological alterations compared with Control + G and ZIF-8-treated groups (p < 0.05). These effects were comparable to those observed with metformin as an anti-hyperglycemia drug. In contrast, nano-formulation of curcumin via ZIF-8 did not enhance its efficacy in glycemic regulation, insa expression, or tissue protection. Overall, curcumin demonstrated potential as a bioactive agent for mitigating hyperglycemia-induced physiological disturbances, underscoring its therapeutic applicability.