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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI
2018
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| Online Access: | http://psasir.upm.edu.my/id/eprint/74955/ http://psasir.upm.edu.my/id/eprint/74955/1/biomolecules-08-00149.pdf |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ahmed, Qamar Uddin |
| building | UPM Institutional Repository |
| collection | Online Access |
| 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 | 2025-11-15T11:59:49Z |
| format | Article |
| id | upm-74955 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T11:59:49Z |
| publishDate | 2018 |
| publisher | MDPI |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-749552020-04-20T17:06:40Z http://psasir.upm.edu.my/id/eprint/74955/ 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 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. MDPI 2018 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/74955/1/biomolecules-08-00149.pdf Ahmed, Qamar Uddin and Sarian, Murni Nazira and Mat So’ad, Siti Zaiton and Latip, Jalifah and Arief Ichwan, Solachuddin Jauhari and Hussein, Nurlaili Najmie and Taher, Muhammad and Alhassan, Alhassan Muhammad and Hamidon, Hanisuhana and Fakurazi, Sharida (2018) Methylation and acetylation enhanced the antidiabetic activity of some selected flavonoids: in vitro, molecular modelling and structure activity relationship-based study. Biomolecules, 8 (4). pp. 1-22. ISSN 2218-273X, ESSN: 2218-273X 10.3390/biom8040149 |
| spellingShingle | 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 |
| 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 |
| url | http://psasir.upm.edu.my/id/eprint/74955/ http://psasir.upm.edu.my/id/eprint/74955/ http://psasir.upm.edu.my/id/eprint/74955/1/biomolecules-08-00149.pdf |