Phenolics from Chrozophora oblongifolia Aerial Parts as Inhibitors of α-Glucosidases and Advanced Glycation End Products: In-Vitro Assessment, Molecular Docking and Dynamics Studies.
Hossam Mohamed AbdallahAlbraa T KashegariAkram A ShalabiKhaled M DarwishAli M El HalawanyMardi M AlgandabySabrin Ragab Mohamed IbrahimGamal Abdallah MohamedAshraf B Abdel-NaimAbdulrahman E KoshakPeter ProkschSameh S ElhadyPublished in: Biology (2022)
Modern life is associated with low physical activity that leads to the accumulation of fats, gaining more weight, and obesity. Accumulation of fat in the abdomen region contributes to diabetes via insulin resistance and hyperglycemia. Polyphenols are major plant constituents that exert antidiabetic activity through different mechanisms, including radicle scavenging activity, regulation of glucose uptake, and inhibition of fat and polysaccharide hydrolysis in addition to their inhibitory role regarding the formation of advanced glycation end products (AGEs). Chemical investigation of C. oblongifolia aerial parts resulted in the isolation of five major compounds: apeginin-7-O-β-D-glucoside ( 1 ), quercetin-3-O-β-D-glucuronic acid ( 2 ), quercetin-3-O-β-D-galacturonic acid ( 3 ), rutin ( 4 ), and 1,3,6-trigalloyl glucose ( 5 ). The isolated compounds were tested for their antioxidant and AGEs formation, α-glucosidase, and lipase inhibitory activities. Compound 5 revealed the highest antioxidant and AGEs inhibitory activity in bovine serum albumin (BSA)-methylglyoxal, BSA-fructose, and arginine-methylglyoxal models. Moreover, it exhibited a potent inhibitory profile on Saccharomyces cerevisiae α-glucosidases compared to the positive control, acarbose. Compound ( 5 ) further depicted promising binding affinity and stability towards the human intestinal maltase-glucoamylase α-glucosidases, which is a diabetes-related therapeutic target, through coupled molecular docking and dynamics studies. The obtained results encourage the usage of 1,3,6-trigalloyl glucose in the management of diabetes and its complications. However, detailed in-vivo studies for this compound should be performed.
Keyphrases
- molecular docking
- type diabetes
- insulin resistance
- glycemic control
- physical activity
- blood glucose
- molecular dynamics simulations
- saccharomyces cerevisiae
- cardiovascular disease
- adipose tissue
- weight loss
- case control
- anti inflammatory
- metabolic syndrome
- oxidative stress
- body mass index
- endothelial cells
- high fat diet
- nitric oxide
- high fat diet induced
- skeletal muscle
- fatty acid
- single cell
- dna binding
- body weight
- sleep quality
- induced pluripotent stem cells