PMID- 25216353
OWN - NLM
STAT- MEDLINE
DCOM- 20150528
LR  - 20240323
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 9
DP  - 2014
TI  - Diosgenin from Dioscorea bulbifera: novel hit for treatment of type II diabetes 
      mellitus with inhibitory activity against alpha-amylase and alpha-glucosidase.
PG  - e106039
LID - 10.1371/journal.pone.0106039 [doi]
LID - e106039
AB  - Diabetes mellitus is a multifactorial metabolic disease characterized by 
      post-prandial hyperglycemia (PPHG). alpha-amylase and alpha-glucosidase inhibitors aim to 
      explore novel therapeutic agents. Herein we report the promises of Dioscorea 
      bulbifera and its bioactive principle, diosgenin as novel alpha-amylase and 
      alpha-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 alpha-amylase and 
      alpha-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 alpha-amylase and 
      alpha-glucosidase inhibition upto 70.94 +/- 1.24% and 81.71 +/- 3.39%, respectively. 
      Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to 
      alpha-amylase indicated by lowering of both Km and Vm. Interaction studies revealed 
      the quenching of intrinsic fluorescence of alpha-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 alpha-amylase. Diosgenin interacted with 
      two catalytic residues (Asp352 and Glu411) from alpha-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.
FAU - Ghosh, Sougata
AU  - Ghosh S
AD  - Institute of Bioinformatics and Biotechnology, University of Pune, Pune, India.
FAU - More, Piyush
AU  - More P
AD  - Institute of Bioinformatics and Biotechnology, University of Pune, Pune, India.
FAU - Derle, Abhishek
AU  - Derle A
AD  - Institute of Bioinformatics and Biotechnology, University of Pune, Pune, India.
FAU - Patil, Ajay B
AU  - Patil AB
AD  - Garware Research Centre, Department of Chemistry, University of Pune, Pune, 
      India.
FAU - Markad, Pramod
AU  - Markad P
AD  - Garware Research Centre, Department of Chemistry, University of Pune, Pune, 
      India.
FAU - Asok, Adersh
AU  - Asok A
AD  - Centre for Research in Nanotechnology and Science, Indian Institute of Technology 
      Bombay, Powai, Mumbai, India.
FAU - Kumbhar, Navanath
AU  - Kumbhar N
AD  - Institute of Bioinformatics and Biotechnology, University of Pune, Pune, India.
FAU - Shaikh, Mahemud L
AU  - Shaikh ML
AD  - National Centre for Cell Science, University of Pune Campus, Ganeshkhind, Pune, 
      India.
FAU - Ramanamurthy, Boppana
AU  - Ramanamurthy B
AD  - National Centre for Cell Science, University of Pune Campus, Ganeshkhind, Pune, 
      India.
FAU - Shinde, Vaishali S
AU  - Shinde VS
AD  - Garware Research Centre, Department of Chemistry, University of Pune, Pune, 
      India.
FAU - Dhavale, Dilip D
AU  - Dhavale DD
AD  - Garware Research Centre, Department of Chemistry, University of Pune, Pune, 
      India.
FAU - Chopade, Balu A
AU  - Chopade BA
AD  - Department of Microbiology, University of Pune, Pune, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140912
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Plant Extracts)
RN  - EC 3.2.1.1 (alpha-Amylases)
RN  - EC 3.2.1.20 (alpha-Glucosidases)
RN  - K49P2K8WLX (Diosgenin)
SB  - IM
MH  - Animals
MH  - Catalytic Domain
MH  - Circular Dichroism
MH  - Diabetes Mellitus, Experimental/*drug therapy/*enzymology/pathology
MH  - Dioscorea/*chemistry
MH  - Diosgenin/chemistry/pharmacology/*therapeutic use
MH  - Enzyme Inhibitors/isolation & purification/pharmacology/*therapeutic use
MH  - Intestines/enzymology
MH  - Kinetics
MH  - Mice
MH  - Molecular Docking Simulation
MH  - Plant Extracts/pharmacology/therapeutic use
MH  - Protein Binding/drug effects
MH  - Spectrometry, Fluorescence
MH  - Sus scrofa
MH  - alpha-Amylases/*antagonists & inhibitors/metabolism
MH  - alpha-Glucosidases/*metabolism
PMC - PMC4162539
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/09/13 06:00
MHDA- 2015/05/29 06:00
PMCR- 2014/09/12
CRDT- 2014/09/13 06:00
PHST- 2014/02/19 00:00 [received]
PHST- 2014/07/27 00:00 [accepted]
PHST- 2014/09/13 06:00 [entrez]
PHST- 2014/09/13 06:00 [pubmed]
PHST- 2015/05/29 06:00 [medline]
PHST- 2014/09/12 00:00 [pmc-release]
AID - PONE-D-14-07023 [pii]
AID - 10.1371/journal.pone.0106039 [doi]
PST - epublish
SO  - PLoS One. 2014 Sep 12;9(9):e106039. doi: 10.1371/journal.pone.0106039. 
      eCollection 2014.