Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study
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...
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MDPI AG
2018-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/8/4/149 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Qamar Uddin Ahmed |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T18:55:01Z |
| format | Article |
| id | doaj.art-3b1b73f25902455cbaca669d9a0ed958 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-10T18:55:01Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj.art-3b1b73f25902455cbaca669d9a0ed9582022-12-22T01:37:10ZengMDPI AGBiomolecules2218-273X2018-11-018414910.3390/biom8040149biom8040149Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based StudyQamar Uddin Ahmed0Murni Nazira Sarian1Siti Zaiton Mat So'ad2Jalifah Latip3Solachuddin Jauhari Arief Ichwan4Nurlaili Najmie Hussein5Muhammad Taher6Alhassan Muhammad Alhassan7Hanisuhana Hamidon8Sharida Fakurazi9Department of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang DM, MalaysiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang DM, MalaysiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang DM, MalaysiaSchool of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, MalaysiaFaculty of Dentistry, International Islamic University Malaysia, Kuantan 25200, Pahang DM, MalaysiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang DM, MalaysiaDepartment of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang DM, MalaysiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang DM, MalaysiaDepartment of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang DM, MalaysiaLaboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, MalaysiaFlavonoids 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.https://www.mdpi.com/2218-273X/8/4/149flavonoidstype 2 diabetes mellitusRIN-5F pancreatic cells3T3-L1 pre-adipocytesadipokinesSARmolecular docking |
| spellingShingle | 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 Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study Biomolecules flavonoids type 2 diabetes mellitus RIN-5F pancreatic cells 3T3-L1 pre-adipocytes adipokines SAR molecular docking |
| title | Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study |
| title_full | Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study |
| title_fullStr | Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study |
| title_full_unstemmed | Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study |
| title_short | Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study |
| title_sort | methylation and acetylation enhanced the antidiabetic activity of some selected flavonoids in vitro molecular modelling and structure activity relationship based study |
| topic | flavonoids type 2 diabetes mellitus RIN-5F pancreatic cells 3T3-L1 pre-adipocytes adipokines SAR molecular docking |
| url | https://www.mdpi.com/2218-273X/8/4/149 |
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