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<p>Diabetes mellitus (DM) is a chronic metabolic disorder marked by persistent hyperglycaemia due to impaired insulin secretion or resistance. Enzymes like α-amylase and α-glucosidase are involved in carbohydrate digestion and glucose absorption, making them crucial targets for anti-diabetic therapy. Black rice bran (BRB), rich in flavonoids, has demonstrated anti-diabetic potential, though the specific bioactive compounds remain underexplored. So, in this study, the anti-diabetic potential of BRB flavonoids against α-amylase (PDB ID: 4W93) and α-glucosidase (PDB ID: 8CB1) is computationally evaluated. The structural quality of the selected proteins was validated <i>via</i> Ramachandran plot, ERRAT, and ProSA-Web. Seven flavonoids namely apigenin, isorhamnetin, kaempferol, luteolin, myricetin, quercetin, and tricin were retrieved from PubChem, optimized, and screened for drug-likeness using Lipinski’s Rule of Five (LRO5) and Molsoft. Six compounds passed the LRO5 and were subjected to ADMET and toxicity profiling <i>via</i> pkCSM which indicated good pharmacokinetic properties with no predicted hepatotoxicity or Ames mutagenicity. On docking these phytochemicals using the CDOCKER protocol (BIOVIA Discovery Studio Client 2023) revealed strong interactions. The result shows that kaempferol reported with highest binding affinity for α-amylase (- 303.139&#xa0;kcal/mol) interacting with HIS A:305 and ASP A:197 through conventional hydrogen bonding (CHB). Furthermore, quercetin demonstrated the strongest binding to α-glucosidase (- 152.4006&#xa0;kcal/mol), targeting ASP A:282, HIS A:674, and ASP A:404 amino acid residues through CHB. In addition to molecular docking, 100 ns molecular dynamics simulations were performed for the kaempferol-α-amylase and quercetin-α-glucosidase complexes to assess the stability and binding persistence. This study highlights kaempferol and quercetin from BRB as promising α-amylase and α-glucosidase inhibitors, respectively. Their strong binding affinity, favourable drug-likeness, and ADMET profiles support their potential as lead hits for anti-diabetic drug development. Further in-vitro and in-vivo research are recommended to validate these findings and elucidate their mechanisms of action.</p> Graphical abstract <p></p>

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Computational validation of black rice Bran (Oryza sativa L.) flavonoids as potential anti-diabetic phytochemicals via targeting alpha-amylase and alpha-glucosidase Inhibition

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月13日

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  • Bedanta Bhattacharjee,
  • K. Sandhanam,
  • Rakib Amin,
  • Nikita Dey,
  • Prachurjya Basumatary,
  • Dimpi Kurmi,
  • Karan Nandi,
  • Ram Kumar Sahu,
  • Damanbhalang Rynjah,
  • Arzoo Newar,
  • Abdul Baquee Ahmed

摘要

Diabetes mellitus (DM) is a chronic metabolic disorder marked by persistent hyperglycaemia due to impaired insulin secretion or resistance. Enzymes like α-amylase and α-glucosidase are involved in carbohydrate digestion and glucose absorption, making them crucial targets for anti-diabetic therapy. Black rice bran (BRB), rich in flavonoids, has demonstrated anti-diabetic potential, though the specific bioactive compounds remain underexplored. So, in this study, the anti-diabetic potential of BRB flavonoids against α-amylase (PDB ID: 4W93) and α-glucosidase (PDB ID: 8CB1) is computationally evaluated. The structural quality of the selected proteins was validated via Ramachandran plot, ERRAT, and ProSA-Web. Seven flavonoids namely apigenin, isorhamnetin, kaempferol, luteolin, myricetin, quercetin, and tricin were retrieved from PubChem, optimized, and screened for drug-likeness using Lipinski’s Rule of Five (LRO5) and Molsoft. Six compounds passed the LRO5 and were subjected to ADMET and toxicity profiling via pkCSM which indicated good pharmacokinetic properties with no predicted hepatotoxicity or Ames mutagenicity. On docking these phytochemicals using the CDOCKER protocol (BIOVIA Discovery Studio Client 2023) revealed strong interactions. The result shows that kaempferol reported with highest binding affinity for α-amylase (- 303.139 kcal/mol) interacting with HIS A:305 and ASP A:197 through conventional hydrogen bonding (CHB). Furthermore, quercetin demonstrated the strongest binding to α-glucosidase (- 152.4006 kcal/mol), targeting ASP A:282, HIS A:674, and ASP A:404 amino acid residues through CHB. In addition to molecular docking, 100 ns molecular dynamics simulations were performed for the kaempferol-α-amylase and quercetin-α-glucosidase complexes to assess the stability and binding persistence. This study highlights kaempferol and quercetin from BRB as promising α-amylase and α-glucosidase inhibitors, respectively. Their strong binding affinity, favourable drug-likeness, and ADMET profiles support their potential as lead hits for anti-diabetic drug development. Further in-vitro and in-vivo research are recommended to validate these findings and elucidate their mechanisms of action.

Graphical abstract