Diosgenin from Dioscorea bulbifera: Novel Hit for Treatment of Type II Diabetes Mellitus with Inhibitory Activity against alpha-Amylase and alpha-Glucosidase
DSpace at IIT Bombay
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Title |
Diosgenin from Dioscorea bulbifera: Novel Hit for Treatment of Type II Diabetes Mellitus with Inhibitory Activity against alpha-Amylase and alpha-Glucosidase
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Creator |
GHOSH, S
MORE, P DERLE, A PATIL, AB MARKAD, P ASOK, A KUMBHAR, N SHAIKH, ML RAMANAMURTHY, B SHINDE, VS DHAVALE, DD CHOPADE, BA |
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Subject |
CRYSTAL-STRUCTURE
ANTIDIABETIC ACTIVITY STEROIDAL SAPOGENINS STRUCTURAL-ANALYSIS YAM DIOSCOREA BITTER YAM RATS EXTRACT COMPLEX TARGETS |
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Description |
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, H-1 NMR and C-13 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.
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Publisher |
PUBLIC LIBRARY SCIENCE
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Date |
2014-12-29T06:31:32Z
2014-12-29T06:31:32Z 2014 |
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Type |
Article
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Identifier |
PLOS ONE, 9(9)
1932-6203 http://dx.doi.org/10.1371/journal.pone.0106039 http://dspace.library.iitb.ac.in/jspui/handle/100/17316 |
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Language |
English
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