Withania somnifera: The Wonder Plant with Withanolide E and J Inhibit Inflammatory Mediator AP-1 Factor

Background: Inflammation is a natural biological response of the body tissues to harmful stimuli, such as damaged cells, irritants or pathogens, and it is a protective response involving blood vessels, immune cells and molecular mediators. Activator Protein-1 (AP-1) is a dimer composed of both homo and hetero dimers with jun and fos subfamilies. The heterodimer cfos-cjun complex is upregulated in several inflammatory diseases such as asthma, rheumatoid arthritis, psoriasis etc. Since ancient times, several plants have been used as anti-inflammatory sources. Withania somnifera is a vital plant having well-documented anti-inflammatory properties. In this study, the phytochemicals of Withania somnifera are used to study the inhibitory effect on the inflammatory mediator AP-1 factor. Objective: Determining the inhibitory effect of Withania somnifera phytochemicals against AP-1 factor (cfos-cjun complex). Methods: In the present study, the phytochemicals of Withania somnifera were retrieved from the IMPPAT database. All the retrieved molecules were employed to screen in-silico pharmacological properties using in-silico tools such as SwissADME and ProTox II. Further, molecular interactions of receptors and ligands were carried out by the Autodock 4.1 tool. Results: A total of 90 phytochemicals of Withania somnifera were subjected to the IMPPAT database. Among those, 21 Phytochemicals showed the appropriate drug similarity characteristics. The Autodock 4.1 tool was used to analyse the binding effect of these 21 phytochemicals. Withanolide E and Withanolide J molecules showed excellent inhibitory action compared to others. The interaction pattern showed that SER and ARG amino acids participate in the formation of drug hydrogen bonds. Conclusion: Among the 90 phytochemicals of Withania somnifera, only two molecules showed potential ligand binding ability. Further, in-vitro studies may validate the findings.