Objectives

Adenosine receptor signaling and suppressing potential pathways such as the aryl hydrocarbon receptor (AHR) and takeda G-protein-coupled receptor-5(TGR5) have been identified as potential targets 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 receptor (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 structures 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 agonist 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 pharmacokinetic characteristics, metabolite production in animals, and the effects of chronic daily absorption.

中文翻译：

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芦荟苷通过多种近期肥胖途径对产热和抗炎过程的分子作用：通过计算机分析发现抗肥胖药物

目标

腺苷受体信号传导和抑制潜在途径，如芳烃受体 (AHR) 和武田 G 蛋白偶联受体 5 (TGR5) 已被确定为增强代谢健康的潜在靶点。某些腺苷受体 (AR) 配体已被认为可以减少炎症并改善脂肪组织的生热作用。

方法

这项研究采用腺苷受体和其他潜在靶标的计算机生物分子部分来了解 Asperuloside 的作用机制。此外，使用肥胖模型中的计算分析检查了 Asperuloside（一种具有 A2A 腺苷受体 (A2AAR) 激动剂和 A3 腺苷受体 (A3AR) 激动剂活性的双重作用配体）的抗肥胖潜力。通过不同的蛋白质结构研究了Asperuloside对炎症和产热的影响，例如具有激动剂的A2AAR复合物/具有拮抗剂的A2AAR复合物、具有结合半肽（作为A3腺苷受体）的视紫红质突变体、具有合成激动剂23H的人TGR5复合物、和AHR受体拮抗作用。

结果

研究发现，Asperuloside 对腺苷受体的结合位点具有治疗亲和力，并揭示了一种新的结合相互作用，有助于减少炎症和改善生热介导的肥胖。

结论

Asperuloside 可能通过其具有 A2AAR 和 A3AR 激动剂活性的双重作用配体具有抗肥胖作用。这项研究为了解 Asperuloside 的作用机制及其作为抗肥胖药物的潜在用途迈出了重要一步。体内测试将有助于确定其药代动力学特征、动物体内代谢产物的产生以及长期日常吸收的影响。