Inhibition of TNF-α and IL-1 by compounds from selected plants for rheumatoid arthritis therapy: &lt;i&gt;In vivo&lt;/i&gt; and &lt;i&gt;in silico&lt;/i&gt; studies

Shengkang Xu,Hao Peng,Na Wang,Meng Zhao

doi:10.4314/tjpr.v17i2.12

Abstract

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

Highlights

Rheumatoid arthritis (RA) is an autoimmune disorder in which the immune system targets the joints thereby causing pain and swelling [1]
The evaluation of the immune-modulatory activities of the herbal compounds and their medicinal potential for the treatment of RA revealed that these compounds possessed strong inhibitory effects on monocytes
The molecular docking scores of the herbal compounds against TNF-α (PDB ID: 2AZ5) and IL-1 (PDB ID: 2L5X) are presented in Table 2, which depicts the scores and results based on ascending order of the re-rank score, and the MolDock scores and interaction energies

Summary

Introduction

Rheumatoid arthritis (RA) is an autoimmune disorder in which the immune system targets the joints thereby causing pain and swelling [1]. The ultimate goal of treatment of RA is to reduce the pain and inflammation associated with the disease which is usually characterized by cellular activation that leads to autoimmunity. The chronic phase of the disease manifests in tissue injury and inflammation due to the release of cytokines such as TNF-α and IL–1 [6].These cytokines are produced by mononuclear leukocytes in response to numerous agents such as endotoxin and lipopolysaccharide [7,8]. In several RA cases, the innate immune cells become activated and release a spectrum of pro-inflammatory mediators such as the TNF-α and IL-1 [9]. TNF-α andIL-1 are involved in tissue damage and joint inflammation [10,11]

Results

Discussion

Conclusion