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Volume 5, Issue 1
  • ISSN: 0250-6882
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Abstract

Background

Type 2 diabetes is a heterogeneous disease characterized by high blood glucose levels. Its prevalence is increasing as a result of lifestyle, related genes expression, and insufficient insulin signaling. The activation or inhibition of some proteins in the insulin signaling pathway play a vital role in glucose uptake into the cells and in maintaining serum glucose homeostasis. Phosphoinositide-3-kinase (PI3K), 3-phosphoinositide-dependent protein kinase-1 (PDK1), Protein kinase B [PKB, also known as the serine and threonine kinase (AKT)], and Rac family small GTPase 1 (RAC1) are key proteins that play important roles in the liberation of Glucose Transported-4 (GLUT4) vesicle, and consequently the uptake of glucose in response to the insulin signal of hyperglycemia.

Objective

In this study, we have focused on the route of targeting insulin signaling proteins for decreasing insulin resistance by targeting the four proteins, PI3K, PDK1, AKT, and RAC1, using studies.

Methods

Docking experiments, using AutoDock algorithms, were performed to predict the activity of eight recently purified derivatives of (GT) and (4-hydroxybenzoic acid, beta-amyrin, beta-sitosterol, chlorogenic acid, lupeol, lupeol-trifluoroacetate, myo-inositol, and stigmasterol) on the insulin signaling proteins. The SwissADME website was used to predict ADMEtox properties for the eight derivatives of the above-mentioned medicinal plants.

Results

Most of the and derivatives have shown variable levels of activation, mainly on the PDK1 and AKT pathways, and to a much lesser extent on the PI3K and RAC1 pathways.

Conclusion

The results have indicated that and derivatives can be potent anti-diabetic drugs, namely in targeting PDK1 and AKT pathways.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Ligand-protein Docking of Gundelia tournefortii and Ocimum basilicum Derivatives in Scanning Hub Protein Targets (PI3K, PDK1, AKT, and RAC1) of the Insulin Signaling Pathway and ADME/Tox Drug Properties
NEW Emirates Medical J 5, e02506882306428 (2024); https://doi.org/10.2174/0102506882306428240613104944
/content/journals/nemj/10.2174/0102506882306428240613104944
/content/journals/nemj/10.2174/0102506882306428240613104944
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  • Article Type:     Research Article
Keyword(s): Diabetes mellitus; Glucose level; Gundelia tournefortii; In silico; Ocimum basilicum; Phytochemicals

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