Polyphenol-enriched extract from pearl millet (Pennisetum glaucum) inhibits key enzymes involved in post prandial hyper glycemia (α-amylase, α-glucosidase) and regulates hepatic glucose uptake

Inhibition of carbohydrate digestion and modulation of glucose uptake are the major mechanisms of anti-hyperglycemic potential known to be played by phenolics; but the role of archaeologically relevant staple pearl millet (Pennisetum glaucum; PM), is still much unknown. A combined approach using in vitro inhibitory data and in silico docking of PM phenolics against key players of glucose homeostasis (salivary α-amylase: SA; pancreatic α-amylase: PA; α-glucosidase, maltase-glucoamylase: MGAM and GLUT2) were carried out. Observed notable inhibition with HHB299 having the most relevant effect (IC50: 73.06 ± 0.37 μg/mL for α-amylase; IC50: 73.80 ± 0.12 μg/mL for α-glucosidase). The role of phenolics on basal glucose uptake into hepatocytes, revealed a maximum of 241.25% in PC612 and the least of 198.1% in HHB67imp. Virtual screening via docking found that 3, 4-Di-OMe luteolin, acacetin as the major flavonoids while salicylic acid, melilotic acid as the key phenolic acids contributing towards the observed anti-diabetic effect. Further, structure-activity relationship (SAR) identified the critical functional groups required for the protein-phenolic molecular interactions. This report validates the role of PM phenolics in inhibiting carbolytic enzymes and regulating GLUT and thus probes the link towards the anti-diabetic potential.