Inhibition of TNF-α and IL-1 by compounds from selected plants for rheumatoid arthritis therapy: In vivo and in silico studies
Purpose: To investigate the inhibitory activities of herbal compounds from Curcuma longa, Sophora japonica and Camellia sinensis against tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1) using in vivo and in silico tools.
Methods: The extracts of the medicinal herbs (Curcuma longa, Sophora japonica and Camellia sinensis) were evaluated for immune-modulatory activities based using neutrophil oxidative burst assay. The compounds present in the medicinal herbs were screened for their inhibitory effects against TNF-α (PDB ID: 2AZ5) and IL-1 (PDB ID: 2L5X) using Molegro Virtual Docker 6.0 (MVD). The stabilities of the top docking poses were confirmed by Molecular Dynamics (MD) simulation run for 20 nanoseconds (ns).
Results: The herbal compounds exerted strong inhibitory effects against TNF-α (PDB ID: 2AZ5) and IL- 1 (PDB ID: 2L5X), implying their therapeutic potential for use in rheumatoid arthritis (RA). Of the compounds, curcumin diglucoside and curcumin monoglucoside showed the strongest inhibitory effects on monocytes, with inhibitory levels of 82.75 and 81.34 %, respectively, while eugenin had the weakest inhibitory activity (11.12 %). In addition, molecular docking scores were consistent with the in vivo results, and revealed strong inhibitory effects of curcumin diglucoside and curcumin monoglucoside against TNF-α and IL-1.
Conclusion: Herbal compounds present in Curcuma longa, Sophora japonica and Camellia sinensis possess strong inhibitory effects against the pro-inflammatory cytokines TNF-α and IL-1. Thus, these compounds have therapeutic potentials that can be exploited for the treatment of RA.
Keywords: Curcuma longa, Sophora japonica, Camellia sinensis, Rheumatoid arthritis, Cytokines, TNF-α, IL-1, Immuno-modulation, Molecular docking