Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study

Qamar Uddin Ahmed, Murni Nazira Sarian, Siti Zaiton Mat So'ad, Jalifah Latip, Solachuddin Jauhari Arief Ichwan, Nurlaili Najmie Hussein, Muhammad Taher, Alhassan Muhammad Alhassan, Hanisuhana Hamidon, Sharida Fakurazi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Flavonoids have been reported to exert antihyperglycemic effects and have potential to enhance the current therapy options against type 2 diabetes mellitus. However, the structure activity relationships (SAR) studies of flavonoids against this disease have not been thoroughly comprehended. Hence, in the present study, 14 structurally related flavonoids viz. wogonin, techtochrysin, norwogonin, isoscutellarein, hypolaetin, kaempferol, quercetin, methyl ether of wogonin, acetate of wogonin, acetate of norwogonin, 8-hydroxy-7-methoxyflavone, chrysin, (+)-catechin and (-)-epicatechin were taken into account for in vitro antidiabetic evaluation. Cell viability of RIN-5F pancreatic cells and 3T3-L1 pre-adipocyte cells was initially tested, then an insulin secretion assay of RIN-5F as well as adipogenesis and glucose uptake measurements of adipocyte were investigated. Subsequently, protein expressions study through adipokines measurement (leptin, adiponectin, TNF-α, RBP-4) via enzyme-linked immunosorbent assay (ELISA) kit, Western blotting analysis against GLUT4 and C/EBP-α as well as molecular docking against GLUT1 were analyzed. The results from cell culture antidiabetic assays (insulin secretion, adipogenesis, and glucose uptake), protein expressions and molecular docking pointed that the methoxy group at position C-8 is responsible for antidiabetic property of selected flavonoids via glucose uptake mechanism indicated by up regulation of GLUT4 and C/EBP-α expressions. The mechanism could be enhanced by the addition of an acetate group at C-5 and C-7 of the flavone skeleton.

Original languageEnglish
JournalBiomolecules
Volume8
Issue number4
DOIs
Publication statusPublished - 15 Nov 2018

Fingerprint

Acetylation
Methylation
Molecular modeling
Structure-Activity Relationship
Molecular Structure
Hypoglycemic Agents
Flavonoids
Molecular structure
Thermodynamic properties
Assays
Adipogenesis
flavone
Acetates
Catechin
Adipocytes
Glucose
Insulin
3T3-L1 Cells
Methyl Ethers
Immunosorbents

Keywords

  • 3T3-L1 pre-adipocytes
  • adipokines
  • flavonoids
  • molecular docking
  • RIN-5F pancreatic cells
  • SAR
  • type 2 diabetes mellitus

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids : In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study. / Ahmed, Qamar Uddin; Sarian, Murni Nazira; Mat So'ad, Siti Zaiton; Latip, Jalifah; Arief Ichwan, Solachuddin Jauhari; Hussein, Nurlaili Najmie; Taher, Muhammad; Alhassan, Alhassan Muhammad; Hamidon, Hanisuhana; Fakurazi, Sharida.

In: Biomolecules, Vol. 8, No. 4, 15.11.2018.

Research output: Contribution to journalArticle

Ahmed, Qamar Uddin ; Sarian, Murni Nazira ; Mat So'ad, Siti Zaiton ; Latip, Jalifah ; Arief Ichwan, Solachuddin Jauhari ; Hussein, Nurlaili Najmie ; Taher, Muhammad ; Alhassan, Alhassan Muhammad ; Hamidon, Hanisuhana ; Fakurazi, Sharida. / Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids : In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study. In: Biomolecules. 2018 ; Vol. 8, No. 4.
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