Bioactive Apigenin‐7‐O‐β‐Glucoside and Rosmarinic Acid Molecules From Two Nepeta Species: Bioactivity‐Guided Isolation, In Vitro Evaluations, Pharmacokinetic and In Silico Approaches as Metabolic Enzyme Inhibition Agents

ABSTRACT Introduction In this study, apigenin‐7‐ O ‐ β ‐glucoside (AGL) was isolated from Nepeta nuda ; also, rosmarinic acid (RA) was isolated from N. aristata and N. nuda . Objectives The aim of this study is to investigate the enzyme inhibitory, DNA protective, and antibacterial effects of AGL and RA isolated from two Nepeta species. Material and Methods 1D and 2D NMR spectra and an MS chromatogram were recorded to identify AGL and RA. The antibacterial and DNA protection activities, enzyme inhibition, and kinetics investigated of AGL and RA. Molecular interactions, molecular dynamics (MD) simulations, molecular mechanics Poisson–Boltzmann surface area (MM‐PBSA) calculations, density functional theory (DFT), molecular electrostatic potential (MEP) analyses, and prediction of activity spectra for substances (PASS) predictions for RA and AGL were investigated for the first time to evaluate the activity results. Results In this context, the inhibitory properties of AGL were higher in urease, α‐amylase, and tyrosinase, whereas RA has a higher inhibitory activity on lipase, CA, and urease. In addition, AGL and RA showed effective antimicrobial activity against Staphylococcus aureus , while it also was effective DNA and deoxyribose protective activities. The stability of the complex formed by lipase, CA, and urease with RA and by tyrosinase and α‐amylase with AGL was determined by MD simulations, and the energy results of RA were evaluated by MM‐PBSA analysis. The DFT, MEP analysis, and PASS prediction showed that AGL and RA have a soft structure and can easily exchange electrons. Conclusion According to the results obtained from the current study, AGL and RA were explored as a drug model.