Anti-Inflammatory and Immunomodulatory Phytochemicals for Management of Oral Lichen Planus: A Multi-Omics System Biology and Experimental Assessment

Oral Lichen planus (OLP) is a chronic autoimmune inflammatory disorder where the exact pathophysiology remains unclear, posing challenges to effective treatment. The accumulative evidence suggested that anti-inflammatory and immunomodulatory phytochemicals showed alternative therapeutic effects. Accordingly, the present study selected 28 multimodal phytochemicals (P1 to P28) and further assessed their potency and drug-ability using computer-aided drug design (CADD) and experimental methods. At first, the putative targets for OLP were selected through network pharmacology, and then molecular docking scores with predicted drug-ability profiles recommended that P12 (epicatechin gallate/ECG) be the lead candidate among all. Furthermore, the protein-ligand stability of ECG against the nonsteroidal target cyclooxygenase-2 (COX-2) and the steroidal target Glucocorticoid Receptor (GR) was investigated using molecular dynamics (MD) simulations over 200 ns, and free energy calculations (MM/PBSA) were performed with GROMACS-2020 software. The nontoxic dose for ECG was observed to be > 100 µM in three cell lines (HEK293, Huh7, and THP-1). The gene expression results demonstrated that the COX-2 and the proinflammatory cytokine IL-1β significantly reduced, and the anti-inflammatory cytokine IL-10 slightly increased in a concentration-dependent manner in inflammation-induced (LPS-treated) THP-1 cells. Overall, the systematic computational and experimental results suggested that ECG could be a potent therapeutic option for managing OLP among the listed treatments.

cyclooxygenase‐2 and cytokines expression; molecular docking simulation; multimodal phytochemicals; network pharmacology; oral lichen planus.