Comprehensive Evaluation of Ixoroside: An Iridoid Glycoside From Nepeta Aristata and N. Baytopii, Assessing Antioxidant, Antimicrobial, Enzyme Inhibitory, DNA Protective Properties, with Computational and Pharmacokinetic Analyses

Abstract

Ixoroside, an iridoid glycoside, was isolated from two endemic plants, Nepeta aristata and Nepeta baytopii and its structure was elucidated by comprehensive analysis with NMR and mass spectrophotometers. It was observed that the compound exhibited strong antioxidant activity in phosphomolybdenum-reducing power (55.65 +/- 0.02 mu g/mL), H2O2 (2.97 +/- 0.50 mu g/mL), and superoxide anion scavenging (11.31 +/- 0.19 mu g/mL) activities. It has also been noted that the ixoroside molecule has enzyme inhibitor (7.01 +/- 0.001 mu g/mL for urease, 19.06 +/- 0.51 mu g/mL for AChE, 9.90 +/- 0.5 mu g/mL for BChE, 16.87 +/- 0.08 mu g/mL for alpha-amylase, 4.11 +/- 0.36 mu g/mL for alpha-glucosidase and 2.23 +/- 0.001 mu g/mL for tyrosinase) and DNA protective effect (55.14% for Form I) and antibacterial (10 mm against K. pneumoniae, 9.00 mm against E. faecalis and 11.00 mm against S. aureus, 128 mu g/mL against E. coli and E. faecalis). In silico studies, density functional theory (DFT) and molecular docking were performed to elucidate ixoroside interaction with enzymes. In enzyme inhibition kinetics, ixoroside exhibited strong interaction with urease (K-i, 0.11 mM, mixed-uncompetitive), alpha-glucosidase (K-i, 0.10 mM, noncompetitive) and tyrosinase (Ki, 0.10 mM, noncompetitive). Additionally, BChE was observed to interact strongly with alpha-glucosidase and tyrosinase with binding constants of 0.49, 1.19 and 3.15 mu M in molecular docking. Moreover, the pharmacological properties of ixoroside examined by adsorption, distribution, metabolism, excretion and toxicity (ADMET) showed that the molecule has drug-like properties.