In silico molecular docking study of Andrographis paniculata phytochemicals against TNF-α as a potent anti-rheumatoid drug

Abstract

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine which plays a crucial role in controlling inflammatory responses. The pathway of Rheumatoid arthritis (RA) leading to TNF-alpha is activated by macrophages and quite often by natural killer cells and lymphocytes. In the inflammatory phase, it is believed to be the main mediator and to be anchored with the progression of different diseases such as ankylosing spondylitis, Crohn's disease, and Rheumatoid arthritis (RA). The major goal of this study is to use in silico docking studies to investigate the anti-inflammatory potential of a bioactive molecule from the medicinal plant Andrographis paniculata. The three-dimensional structures of different phytochemicals of A. paniculata were obtained from PubChem database, and the receptor protein was derived from PDB database. Docking analysis was executed using AutoDock vina, and the binding energies were compared. Bisandrographolide A and Andrographidine C revealed the highest score of −8.6 Kcal/mol, followed by, Neoandrographolide (−8.5 Kcal/mol). ADME and toxicity parameters were evaluated for these high scoring ligands and results showed that Andrographidine C could be a potent drug, whereas Neoandrographolide and Bisandrographolide A can be modified in in vitro and can lead to a promising drug. Further, the top scorer (Andrographidine C) and control drug (Leflunomide) were subjected to 100 ns MD Simulation. The protein complex with Andrographidine C had more stable confirmation with lower RMSD (0.28 nm) and higher binding energy (−133.927 +/− 13.866 kJ/mol). In conclusion, Andrographidine C may be a potent surrogate to the disease-modifying anti-rheumatic drugs (DMARD’s) & Non-steroidal anti-inflammatory drugs (NSAID’s) that has fewer or minor adverse effects and can aid in RA management.

Graphical Abstract

Keywords:

• Rheumatoid arthritis
• TNF-α
• molecular docking
• Swiss ADME
• toxicity study
• Andrographis paniculata
• Andrographidine C
• phytochemicals

Acknowledgments

Authors are grateful to CHRIST (Deemed to be University) for all the facilities and support provided in this research. We are also thankful to Dr. Usha Talambedu, Maharani Lakshmi Ammanni College for Women for helping us in Molecular Dynamic simulation studies.

Disclosure statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Funding

The author(s) reported there is no funding associated with the work featured in this article.