<p>Type 2 diabetes mellitus (T2DM) is characterized by elevated blood glucose levels and insulin resistance. Trigonella foenum-graecum (fenugreek) has been extensively reported for its hypoglycemic and insulin-sensitizing properties mediated through multiple biochemical pathways. This study aimed to synthesize copper nanoparticles (CuNPs) using fenugreek seed extract and the investigation of their antidiabetic activity through an integrated in vitro and in silico approach. Qualitative phytochemical analysis confirmed the presence of secondary metabolites. The in vitro enzyme inhibition assays revealed promising suppression of digestive enzymes: α-amylase (88.72%) and α-glucosidase (91.02%) at 500&#xa0;µg/mL, indicating a postprandial glucose-lowering capacity. UV-Vis spectroscopy indicated a distinct surface plasmon resonance peak at 546&#xa0;nm while XRD and FTIR analyses respectively confirmed the crystalline nature and the functional group that were involved in CuNP stabilization. Network pharmacology and molecular docking studies showed significant interactions between the CuNP-ligand conjugates and the diabetes-associated target genes. Moreover, ADMET analysis of the ligands, thymol and anthranilic acid, indicated good oral bioavailability. Overall, the findings demonstrate in vitro antidiabetic activity, while the proposed molecular targets and pathways derived from the network pharmacology and molecular docking analyses were employed as computational, hypotheses-generating approaches and the mechanisms have not been experimentally validated. This integrated phyto-nanoparticle strategy represents a promising cost-effective and sustainable nanotherapeutic approach for diabetes management.</p> Graphical Abstract <p></p>

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In vitro and in silico evaluation of copper nanoparticle-phytoconjugates as multi-target antidiabetic agents

  • R. Meenakshi,
  • S. Sudharson,
  • R. Subashini,
  • S. Abirami,
  • MD Tameem Tabbasum

摘要

Type 2 diabetes mellitus (T2DM) is characterized by elevated blood glucose levels and insulin resistance. Trigonella foenum-graecum (fenugreek) has been extensively reported for its hypoglycemic and insulin-sensitizing properties mediated through multiple biochemical pathways. This study aimed to synthesize copper nanoparticles (CuNPs) using fenugreek seed extract and the investigation of their antidiabetic activity through an integrated in vitro and in silico approach. Qualitative phytochemical analysis confirmed the presence of secondary metabolites. The in vitro enzyme inhibition assays revealed promising suppression of digestive enzymes: α-amylase (88.72%) and α-glucosidase (91.02%) at 500 µg/mL, indicating a postprandial glucose-lowering capacity. UV-Vis spectroscopy indicated a distinct surface plasmon resonance peak at 546 nm while XRD and FTIR analyses respectively confirmed the crystalline nature and the functional group that were involved in CuNP stabilization. Network pharmacology and molecular docking studies showed significant interactions between the CuNP-ligand conjugates and the diabetes-associated target genes. Moreover, ADMET analysis of the ligands, thymol and anthranilic acid, indicated good oral bioavailability. Overall, the findings demonstrate in vitro antidiabetic activity, while the proposed molecular targets and pathways derived from the network pharmacology and molecular docking analyses were employed as computational, hypotheses-generating approaches and the mechanisms have not been experimentally validated. This integrated phyto-nanoparticle strategy represents a promising cost-effective and sustainable nanotherapeutic approach for diabetes management.

Graphical Abstract