Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents

• DOI: 10.1371/journal.pone.0140113
• Publication Date: 2015-10-15T18:08:35Z
• Authors: Sudha Ponnusamy; Saikat Haldar; Fayaj Mulani; Smita Zinjarde; Hirekodathakallu ...; Ameeta RaviKumar
• Keywords: Azadirachta; IC50

Human pancreatic α-amylase (HPA) inhibitors offer an effective strategy to lower postprandial hyperglycemia via control of starch breakdown. Limonoids from Azadirachta indica known for their therapeutic potential were screened inhibition, a anti-diabetic target. Studies carried out reveal mode action so as justify hypoglycemic potential. Of the nine limonoids isolated/semi-synthesized A.indica and azadiradione exhibited inhibition with IC50 value 74.17 68.38 μM, respectively against HPA under in vitro conditions. Further screening on AR42J secretory cell line cytotoxicity bioactivity revealed that gedunin 11.1 13.4μM. Maximal secreted 41.8% 53.4% was seen at 3.5 3.3μM, respectively. Michaelis-Menten kinetics suggested mixed maltopentaose (Ki 42.2, 18.6 μM) (Ki′ 75.8, 37.4 substrate stiochiometry 1:1 both gedunin, The molecular docking simulation indicated plausible π-alkyl alkyl-alkyl interactions between aromatic amino acids inhibitors. Fluorescence CD confirmed involvement tryptophan tyrosine ligand binding HPA. Thermodynamic parameters is enthalpically entropically driven ΔG° -21.25 kJ mol-1 -21.16 Thus, could bind inactivate (anti-diabetic target) may prove be lead drug candidates reduce/control post-prandial hyperglycemia.