Dataset Information

Isolation of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro and In Silico Validation.

ABSTRACT: Withania coagulans (W. coagulans) is well-known in herbal medicinal systems for its high biological potential. Different parts of the plant are used against insomnia, liver complications, asthma, and biliousness, as well as it is reported to be sedative, emetic, diuretic, antidiabetic antimicrobial, anti-inflammatory, antitumor, hepatoprotective, antihyperglycemic, cardiovascular, immuno-suppressive and central nervous system depressant. Withanolides present in W. coagulans have attracted an immense interest in the scientific field due to their diverse therapeutic applications. The current study deals with chemical and biological evaluation of chloroform, and n-butanol fractions of W. coagulans. The activity-guided fractionation of both extracts via multiple chromatographic steps and structure elucidation of pure isolates using spectroscopies (NMR, mass spectrometry, FTIR and UV-Vis) led to the identification of a new withanolide glycoside, withacogulanoside-B (1) from n-butanol extract and five known withanolides from chloroform extract [withanolid J (2), coagulin E (3), withaperuvin C (4), 27-hydroxywithanolide I (5), and ajugin E (6)]. Among the tested compounds, compound 5 was the most potent ?-glucosidase inhibitor with IC50 = 66.7 ± 3.6 µM, followed by compound 4 (IC50: 407 ± 4.5 µM) and compound 2 (IC50: 683 ± 0.94 µM), while no antiglycation activity was observed with the six isolated compounds. Molecular docking was used to predict the binding potential and binding site interactions of these compounds as ?-glucosidase inhibitors. Consequently, this study provides basis to discover specific antidiabetic compounds from W. coagulans.

SUBMITTER: Maher S

PROVIDER: S-EPMC7464911 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Isolation of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro and In Silico Validation.

Maher Saima S Choudhary M Iqbal MI Saleem Farooq F Rasheed Saima S Waheed Imran I Halim Sobia Ahsan SA Azeem Muhammad M Abdullah Iskandar Bin IB Froeyen Matheus M Mirza Muhammad Usman MU Ahmad Sarfraz S

Biology 20200730 8

Withania coagulans (W. coagulans) is well-known in herbal medicinal systems for its high biological potential. Different parts of the plant are used against insomnia, liver complications, asthma, and biliousness, as well as it is reported to be sedative, emetic, diuretic, antidiabetic antimicrobial, anti-inflammatory, antitumor, hepatoprotective, antihyperglycemic, cardiovascular, immuno-suppressive and central nervous system depressant. Withanolides present in W. coagulans ...[more]

PMID: 32751610

Similar Datasets

Project description:Hypercholesterolemia is a mediator for the etiology of cardiovascular diseases, which are characterized as the global leading cause of mortality. We aimed to investigate the inhibitory activity of Withania coagulans compounds against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) of Mus musculus using an extensive in silico approach. The 3D structure of the Hmgcr protein is not yet known, so we performed the homology modeling using MODELLER and SWISS-MODEL tools, followed with structural validation and assessment. The PROCHECK web server showed that the top-ranked homology model from SWISS-MODEL has 93.4% of residues in the most-favorable region, the quality factor was 98%, and the Verify3D score was 91.43%, compared to the other generated models. The druggable protein-binding cavities in a 3D model of Hmgcr were investigated with the aid of commonly prescribed statin compounds using the CB-dock approach. We compiled a 3D compound library of W. coagulans, followed by drug-likeness evaluation, and found 20 eligible compounds. The pattern of consensus residues obtained from the CB-dock procedure was then used for grid-box docking of W. coagulans compounds and statin drugs using AutoDock 4.2, respectively. The results showed that withanolide R (-10.77 kcal/mol), withanolide Q (-10.56 kcal/mol), withanolide J (-10.52 kcal/mol), atorvastatin (-8.99 kcal/mol), simvastatin (-8.66 kcal/mol), and rosuvastatin (-8.58 kcal/mol) were promising candidates that bind Hmgcr protein. The key residues involved in protein-ligand (withanolide R) interactions were Y516, C526, V529, I530, M533, I535, and V537, and the formation of a H-bond was at C526, M533, and I535 residues. M533 was the consensus residue having a tendency to form a H-bond with withanolide Q, too. Molecular dynamics simulations were used to validate the top-ranked docked complexes for the stability of the modeled protein. We also predicted the pharmacokinetic properties of binding affinity-based top-ranked compounds and concluded that they could be used as potential inhibitors of Hmgcr. However, further in vitro and in vivo studies are essential to completing the drug development process.

Dataset Information

Isolation of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro and In Silico Validation.

Publications

Isolation of Antidiabetic Withanolides from <i>Withania coagulans</i> Dunal and Their In Vitro and In Silico Validation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets