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

被引：27

作者：

Ahmed, Qamar Uddin ^{[1
]}

Sarian, Murni Nazira ^{[1
,2
]}

So'ad, Siti Zaiton Mat ^{[1
]}

Latip, Jalifah ^{[3
]}

Ichwan, Solachuddin Jauhari Arief ^{[4
]}

Hussein, Nurlaili Najmie ^{[1
]}

Taher, Muhammad ^{[5
]}

Alhassan, Alhassan Muhammad ^{[1
]}

Hamidon, Hanisuhana ^{[5
]}

Fakurazi, Sharida ^{[2
,6
]}

机构：

[1] Int Islamic Univ Malaysia, Fac Pharm, Dept Pharmaceut Chem, Kuantan 25200, Pahang Dm, Malaysia

[2] Univ Putra Malaysia, Inst Biosci, Lab Vaccines & Immunotherapeut, Serdang 43400, Selangor, Malaysia

[3] Univ Kebangsaan Malaysia, Fac Sci & Technol, Sch Chem Sci & Food Technol, Bangi 43600, Selangor, Malaysia

[4] Int Islamic Univ Malaysia, Fac Dent, Kuantan 25200, Pahang Dm, Malaysia

[5] Int Islamic Univ Malaysia, Dept Pharmaceut Technol, Fac Pharm, Kuantan 25200, Pahang Dm, Malaysia

[6] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Human Anat, Serdang 43400, Selangor, Malaysia

来源：

BIOMOLECULES | 2018年 / 8卷 / 04期

关键词：

flavonoids; type 2 diabetes mellitus; RIN-5F pancreatic cells; 3T3-L1; pre-adipocytes; adipokines; SAR; molecular docking; GLUCOSE-UPTAKE; INSULIN-RESISTANCE; ANTIOXIDANT ACTIVITY; SECRETION; RETINOL-BINDING-PROTEIN-4; DIFFERENTIATION; COMPLICATIONS; ADIPOGENESIS; TRANSPORTER; INHIBITION;

D O I：

10.3390/biom8040149

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-alpha, RBP-4) via enzyme-linked immunosorbent assay (ELISA) kit, Western blotting analysis against GLUT4 and C/EBP-alpha 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-alpha expressions. The mechanism could be enhanced by the addition of an acetate group at C-5 and C-7 of the flavone skeleton.

引用

页数：22

共 52 条

[1] Phytoconstituents from Vernonia glaberrima Welw. Ex O. Hoffm. leaves and their cytotoxic activities on a panel of human cancer cell lines [J].