Comprehending interaction mechanism of natural actives of L. for rheumatoid arthritis using integrative chemoinformatic approaches.

This research delves into the realm of therapeutic potential within natural compounds derived from L., emphasizing a holistic perspective on medications used in human therapy. Rather than confining the study to their primary actions, the research endeavors to unveil molecular targets for these natural compounds, with a specific focus on their potential applicability in the treatment of rheumatoid arthritis (RA). The study focuses on understanding interactions between specific natural actives that target RA. Fifteen RA target proteins were identified from OMIM, GeneScan and PharmaGKB. Their structures were downloaded from RCSB PDB. Two active components of L. were chosen for mass spectrometry investigation. Ligand characteristics were determined using the ADMETlab and SwissADME software tools. Molecular docking was performed, and the top three complexes were simulated for 200 ns, along with identification of free binding energies. The compounds β-sitosterol-IL-10 (-6.50 kcal/mol), colchicine-IL-10 (-6.01 kcal/mol), linoleic acid-IL-10 (-7.22 kcal/mol) and linoleic acid-IL-10 (-7.22 kcal/mol) exhibited best binding energies. β-Sitosterol and colchicine showed the highest stability in simulations, confirmed by molecular mechanics free energy binding calculations. This work provides insights into the molecular interaction of natural compounds against RA targets, offering potential therapeutic anti-RA medications.Communicated by Ramaswamy H. Sarma.