Rosmarinic acid in Perilla frutescens L. as a potential adenosine deaminase inhibitor: Preparation, machine learning validation and binding mechanism study

Gout, a prevalent arthritic disease, can be mitigated by adenosine deaminase (ADA) inhibitors that reduce uric acid production. In this study, the extraction process of rosmarinic acid (RA) from Perilla frutescens L. (P. frutescens) was optimized, and the best yield was 2.22 mg/g. Quantitative structure-activity relationship (QSAR) model was used to predict ADA inhibitors (ADAIs) in potential foods. The random forest model constructed by ChemoPy descriptor was the best (AUC = 0.9648), and five candidate compounds (including RA) were screened. The inhibitory activity of RA on ADA was confirmed in vitro (IC₅₀ = 55.11 μM). Molecular docking showed that ADAIs and ADA were stably bound through hydrogen bonding and hydrophobic interaction. Molecular dynamics (MD) simulation verified the dynamic stability of ADAIs and ADA complexes. This study provides a theoretical basis for RA from P. frutescens extract as a potential compound for the treatment of gout and for the rapid screening of foodborne ADAIs.