Eucommia ulmoides Oliver (EUO) has a long history of medicinal use in China. As a medicinal plant used for tonifying kidney, strengthening bones, relieving pain, and enhancing immunity, EUO is also widely used in the treatment of RA, depression, and osteoporosis. The aqueous extract of EUO has been demonstrated to have a cartilage-protecting effect in a rat model of osteoarthritis, potentially by inhibiting chondrocyte apoptosis and improving cartilage metabolism (35 (
link)). Aucubin (AU), an iridoid glycoside that is an active constituent of EUO, has been extensively studied for the management of neurological diseases (36 (
link)). However, a comprehensive review of its effects and mechanisms is currently unavailable. Therefore, in this study, we investigated the therapeutic potential of AU. The utilization of molecular docking, a technique commonly employed in virtual screening studies, was carried out to identify potential therapeutic targets for AU (37 (
link)).
Primarily, the cheminformatics of Aucubin (AU) was obtained from the PubChem database (38 (
link)) (
https://pubchem.ncbi.nlm.nih.gov/), which included chemical name, molecular formula, CAS, PubChem CID, canonical SMILES, and SDF files. The ACD/Labs software (
https://www.acdlabs.com/), SwissADME online system (39 (
link)) (
http://www.swissadme.ch/) and ADMETlab 2.0 (
https://admetmesh.scbdd.com/) (40 (
link))were used to evaluate the pharmacokinetics and safety profile of AU, including absorption, distribution, metabolism, excretion, and toxicity. PyMOL software (version 1.7.0;
https://pymol.org/) converted AU’s 3D structure, which was downloaded from the PubChem database (41 (
link)) (
http://www.rcsb.org/), from an SDF file to a PDB file while minimizing the energy of small molecules and then saved it as a PDBQT format file. The 3D structures of potential targets were downloaded from the PDB database (
http://www.rcsb.org/). PyMOL software removed water molecules and hetero-ions from the PDB file of the target protein. The protein ligands then underwent hydrogenation and the charge was added in AutoDockTools (42 (
link)) (version 1.5.6) software. Finally, the data were saved as a PDBQT file. The docking box parameters were determined based on the binding region of the protein receptor and original ligand, and the box size was set to 30Å × 30 Å × 30 Å. AutoDock Vina (version 1.1.2;
http://vina.scripps.edu/) software performs refined the semi-flexible molecular docking and calculated the affinity (kcal/mol) of all potential key targets for AU. Generally, the lower the affinity value, the stronger the binding of the small molecule to the receptor. Discovery Studio Visualizer (
https://www.3ds.com/) was used to visualize the 2D schemes of the AU-target protein interaction.
