title: Diosgenin from Dioscorea bulbifera: novel hit for treatment of type II diabetes mellitus with inhibitory activity against α-amylase and α-glucosidase.
abstract: Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus.
authors.affiliation: Institute of Bioinformatics and Biotechnology, University of Pune, Pune, India.
authors.forename: Sougata
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Institute of Bioinformatics and Biotechnology, University of Pune, Pune, India.
authors.forename: Piyush
authors.initials: P
authors.lastname: More
authors.affiliation: Institute of Bioinformatics and Biotechnology, University of Pune, Pune, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Derle
authors.affiliation: Garware Research Centre, Department of Chemistry, University of Pune, Pune, India.
authors.forename: Ajay B
authors.initials: AB
authors.lastname: Patil
authors.affiliation: Garware Research Centre, Department of Chemistry, University of Pune, Pune, India.
authors.forename: Pramod
authors.initials: P
authors.lastname: Markad
authors.affiliation: Centre for Research in Nanotechnology and Science, Indian Institute of Technology Bombay, Powai, Mumbai, India.
authors.forename: Adersh
authors.initials: A
authors.lastname: Asok
authors.affiliation: Institute of Bioinformatics and Biotechnology, University of Pune, Pune, India.
authors.forename: Navanath
authors.initials: N
authors.lastname: Kumbhar
authors.affiliation: National Centre for Cell Science, University of Pune Campus, Ganeshkhind, Pune, India.
authors.forename: Mahemud L
authors.initials: ML
authors.lastname: Shaikh
authors.affiliation: National Centre for Cell Science, University of Pune Campus, Ganeshkhind, Pune, India.
authors.forename: Boppana
authors.initials: B
authors.lastname: Ramanamurthy
authors.affiliation: Garware Research Centre, Department of Chemistry, University of Pune, Pune, India.
authors.forename: Vaishali S
authors.initials: VS
authors.lastname: Shinde
authors.affiliation: Garware Research Centre, Department of Chemistry, University of Pune, Pune, India.
authors.forename: Dilip D
authors.initials: DD
authors.lastname: Dhavale
authors.affiliation: Department of Microbiology, University of Pune, Pune, India.
authors.forename: Balu A
authors.initials: BA
authors.lastname: Chopade
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002942:Circular Dichroism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D027742:Dioscorea / Q000737:chemistry*; D004144:Diosgenin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D007422:Intestines / Q000201:enzymology; D007700:Kinetics; D051379:Mice; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D034421:Sus scrofa; D000516:alpha-Amylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D010936:Plant Extracts; D000516:alpha-Amylases; D000520:alpha-Glucosidases; D004144:Diosgenin