In silico screening of phytoconstituents as potential anti-inflammatory agents targeting NF-κB p65: an approach to promote burn wound healing

Abstract

Chronic burn wounds are frequently characterised by a prolonged and dysregulated inflammatory phase that is mediated by over-activation of NF-κB p65. Synthetic wound healing drugs used for treatment of inflammation are primarily associated with several shortcomings which reduce their therapeutic index. In this scenario, phytoconstituents that exhibit multifaceted biological activities including anti-inflammatory effects have emerged as a promising therapeutic alternative. However, identification and isolation of phytoconstituents from medicinal herbs is a cumbersome method that is linked to profound uncertainty. Hence, present study aimed to identify prospective phytoconstituents as inhibitors of RHD of NF-κB p65 by utilizing in silico approach. Virtual screening of 2821 phytoconstituents was performed against protein model. Out of 2821 phytoconstituents, 162 phytoconstituents displayed a higher binding affinity (≤ −8.0 kcal/mol). These 162 phytoconstituents were subjected to ADMET predictions, and 15 of them were found to satisfy Lipinski’s rule of five and showed favorable pharmacokinetic properties. Among these 15 phytoconstituents, 5 phytoconstituents with high docking scores i.e. silibinin, bismurrayaquinone A, withafastuosin B, yuccagenin, (+)-catechin 3-gallate were selected for molecular dynamics (MD) simulation analysis. Results of MD simulation indicated that withafastuosin B, (+)-catechin 3-gallate and yuccagenin produced a compact and stable complex with protein without significant variations in conformation. Relative binding energy analysis of best hit molecules indicate that withafastuosin B, and (+)-catechin 3-gallate exhibit high binding affinity with target protein among other lead molecules. Findings of study suggest that these phytoconstituents could serve as promising anti-inflammatory agents for treatment of burn wounds by inhibiting the RHD of NF-κB p65.

Communicated by Ramaswamy H. Sarma

Keywords:

• NF-κB p65
• phytoconstituents
• anti-inflammatory agents
• homology modeling
• virtual screening
• molecular dynamics simulation

Acknowledgments

S. Pattnaik, B. Rath, and C. Mohanty are thankful to the School of Applied Sciences, KIIT Deemed to be University, India. S. Kumar duly acknowledge Department of Biotechnology, Govt. of India for BIC project grant (BT/PR40161/BTIS/137/32/2021). S. Pattnaik would like to thank “Council of Scientific and Industrial Research”, Government of India, for providing a junior research fellowship.

Author’s contributions

CM, SK and SP contributed to the conceptualization and design of the study. SK, SM, SP and MKS performed the experiments. SK, SM, CM, and SP performed the data analysis. SK, SP, and BPR drafted the manuscript. SK, SM, CM, SP, MKS and BPR contributed to manuscript revision and editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

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