Molecular Docking and Binding Analysis of Phytochemicals from Artemisia herba-Alba and Coffee Targeting the Adenosine A₂A Receptor

Abstract

Artemisia herba alba is widely used in traditional medicine, particularly in North Africa, while coffee is one of the most consumed beverages worldwide. The use of medicinal plants together with dietary stimulants raises concerns about potential pharmacodynamic and pharmacokinetic interactions, especially at shared molecular targets. This study aimed to investigate the molecular interactions of caffeine, the major active constituents of coffee, and major bioactive constituents of Artemisia herba alba (α thujone and camphor) with the human adenosine A₂A receptor (A₂AR) using in silico molecular docking approaches. Blind molecular docking was performed using AutoDock Vina within PyRx and independently validated using the CB Dock server. Binding affinities, cavity localization, and ligand–receptor interaction profiles were analyzed, and key hydrogen bonding and hydrophobic interactions were characterized. All three ligands bound strongly to the orthosteric pocket of the adenosine A₂A receptor. α‑thujone showed the strongest binding (–6.4 kcal/mol), followed by camphor (–6.1 kcal/mol) and caffeine (–5.8 to –6.1 kcal/mol). Cross‑validation showed that the docking results were robust and reliable, with very small differences between platforms (< 0.3 kcal/mol). The ligands showed different binding patterns: α‑thujone and camphor mainly interacted through hydrophobic contacts, while caffeine formed many hydrogen bonds. These findings suggest that compounds from Artemisia herba‑alba can interact with the adenosine A₂A receptor at the same levels of caffeine, indicating a possible medicinal plant–food interaction. From a public‑health and pharmacological point of view, using Artemisia preparations together with coffee may change the effects of caffeine and should therefore be studied further to ensure safe and informed use.