The molecular Effects of Asperuloside against thermogenesis and anti-inflammatory process through multiple recent obesity pathways: An anti-obesity drug discovery by In-silico Analysis

Objectives: Adenosine receptor signaling and suppressing potential pathways such as the aryl hydrocar-bon receptor (AHR) and takeda G-protein-coupled receptor-5(TGR5) have been identified as potential tar -gets for enhancing metabolic health. Certain adenosine receptor (AR) ligands have been suggested to reduce inflammation and improve thermogenesis in adipose tissue.Methods: This study employed in-silico biomolecular fractions of adenosine receptors and other potential targets to understand the mechanism of action of Asperuloside. Additionally, the anti-obesity potential of Asperuloside, a dual-acting ligand with A2A adenosine receptor (A2AAR) agonist and A3 adenosine recep-tor (A3AR) agonist activities, were examined using computational analysis in the obesity model. The impact of Asperuloside on inflammation and thermogenesis was studied through diverse protein struc-tures such as the A2AAR complex with agonist/A2AAR complex with antagonist, the rhodopsin mutant with bound galphact peptide (as A3 adenosine receptor), The Human TGR5 complex with synthetic ago-nist 23H, and AHR receptors antagonism.Results: The study found that Asperuloside has therapeutic affinity for the binding site of adenosine receptors and revealed a novel binding interaction that helps reduce inflammation and improve thermogenesis-mediated obesity.Conclusion: Asperuloside may have anti-obesity effects through its dual-acting ligand with A2AAR and A3AR agonist activities. This study provides a major step towards understanding the mechanism of action of Asperuloside and its potential use as an anti-obesity drug. In vivo tests will help ascertain its pharma-cokinetic characteristics, metabolite production in animals, and the effects of chronic daily absorption.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).