Inhibitory Effect of Polyphenols from the Whole Green Jackfruit Flour against α-Glucosidase, α-Amylase, Aldose Reductase and Glycation at Multiple Stages and Their Interaction: Inhibition Kinetics and Molecular Simulations

Molecules

Khalid Awadh Al-Mutairi¹  SubbaRao V. Madhunapantula²  Taha Alqadi³  Tejaswini Maradesha⁴  Shashank M. Patil⁴  Ramith Ramu⁴ 

[1] Biology Department, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia;Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR, A DST-FIST Supported Center), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570015, Karnataka, India;Department of Biology, Adham University College, Umm Al-Qura University, Makkah 21955, Saudi Arabia;Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India;

关键词: whole jackfruit;    type 2 diabetes;    phenolic acids;    caffeic acid;    syringic acid;    inhibition kinetics;   

DOI  :  10.3390/molecules27061888

来源: DOAJ

【 摘 要 】

For the first time, α-glucosidase, α-amylase, aldose reductase, and glycation at multiple stages inhibitory assays were used to explore the antidiabetic potential of whole unripe jackfruit (peel with pulp, flake, and seed). Two polyphenols (phenolic acids) with strong antihyperglycaemic activity were isolated from the methanol extract of whole jackfruit flour (MJ) using activity-guided repeated fractionation on a silica gel column chromatography. The bioactive compounds isolated were identified as 3-(3,4-Dihydroxyphenyl)-2-propenoic acid (caffeic acid: CA) and 4-Hydroxy-3,5-dimethoxybenzoic acid (syringic acid: SA) after various physicochemical and spectroscopic investigations. CA (IC₅₀: 8.0 and 26.90 µg/mL) and SA (IC₅₀: 7.5 and 25.25 µg/mL) were identified to inhibit α-glucosidase and α-amylase in a competitive manner with low Ki values. In vitro glycation experiments further revealed that MJ and its components inhibited each stage of protein glycation as well as the generation of intermediate chemicals. Furthermore, CA (IC₅₀: 3.10) and SA (IC₅₀: 3.0 µg/mL) inhibited aldose reductase effectively in a non-competitive manner, respectively. The binding affinity of these substances towards the enzymes examined has been proposed by molecular docking and molecular dynamics simulation studies, which may explain their inhibitory activities. The found potential of MJ in antihyperglycaemic activity via inhibition of α-glucosidase and in antidiabetic action via inhibition of the polyol pathway and protein glycation is more likely to be related to the presence of the phenolic compounds, according to our findings.

【 授权许可】

Unknown