From millets to medicine: ADMET insights into diabetes management with P. sumatrense compounds

Abstract

Diabetes mellitus, a prevalent metabolic disorder characterised by impaired blood glucose regulation, has escalated into a global health crisis, exacerbated by high-glycaemic diets and unhealthy eating habits. While therapeutic agents such as acarbose mitigate diabetes by inhibiting alpha-amylase and alpha-glucosidase, their use is marred by adverse side effects, underscoring the need for safer, plant-based alternatives. This study explores the antidiabetic potential of Little Millet, an underutilised cereal grain with a low glycaemic index, rich in bioactive compounds. Unlike common staples such as wheat and rice, Little Millet contains unique compounds, including octodrine, 18,19-secoyohimban-19-oic acid, and phenylephrine, which were investigated for their novel application in diabetes management. Gas chromatography-mass spectrometry (GCMS) analysis identified 120 bioactive compounds, selected for their abundance and potential bioactivity. These compounds span fatty acids, phenols, flavonoids, organic acids, sugar alcohols, and amino acids, all of which were rigorously docked to alpha-amylase and human maltase-glucoamylase receptors. Notably, key ligands such as chlorogenic acid and 18,19-secoyohimban-19-oic acid exhibited superior binding affinities compared to acarbose, with promising drug-likeness and ADMET profiles, suggesting higher absorption and fewer side effects. A 100-ns dynamics simulation further validated the stability of these compounds, positioning them as viable candidates for diabetes treatment. These findings advance drug design and highlight the potential of incorporating Little Millet into diets for diabetes prevention. Further validation through In-vitro, In-vivo, and clinical studies is essential to fully realise their therapeutic potential. This research also opens avenues for exploring Little Millet in managing related conditions and enhancing its health benefits through breeding programmes.