A computational approach to discover antioxidant and anti-inflammatory attributes of silymarin derived from Silybum marianum by comparison with hydroxytyrosol

Abstract

Medicinal plants possess therapeutic potential for reducing reactive oxygen species (ROS)-mediated cellular damage. Hydroxytyrosol is one of the most potent antioxidants that served as control in the current study, including other synthetic antioxidants to computationally identify the antioxidant properties of Silymarin. The sequences of the receptors IκB kinase (IKK), Kelch-like ECH-associated protein 1 (Keap-1) and mitochondrial transcription factor A (Tfam) were retrieved from UniProtKB and homology modeling was performed using Swiss-Model server. Thereof the molecular docking and dynamic simulation studies were performed using Schrödinger’s software version 11.5. From the current study, it was reported that on comparison of the binding energy of silymarin, hydroxytyrosol, α-tocopherol, ascorbic acid, butylated hydroxy anisole (BHA) and butylated hydroxytoluene (BHT), Silymarin exhibited better affinities with IKK receptor followed by Hydroxytyrosol suggesting it as the best or comparable of all other known antioxidants that could potentially suppress inflammation and other diseases. Also, Silymarin exhibited poorest binding affinity with Tfam promoting mitochondrial biogenesis, thereby scavenging ROS. However, with Keap-1, Silymarin is ranked 4^th in the list, whereas hydroxytyrosol exhibited highest binding affinity to release oxidative stress. The stability of docked complexes made us conclude that Silymarin has comparable antioxidant properties to hydroxytyrosol, better anti-inflammatory potential and mitochondrial biogenesis enhancing properties to ultimately reduce oxidative stress. Now it can be tested further for in vitro or in vivo studies as potential drug against oxidative insult.

Communicated by Ramaswamy H. Sarma

Keywords:

• Homology modeling
• molecular docking
• molecular dynamic simulation
• inflammation
• antioxidant
• mitochondrial biogenesis

Acknowledgments

We acknowledge Department of Pharmaceutical Sciences, Maharshi Dayanand University for providing us required software to carry out this research. We also want to acknowledge "DBT Builder Maharshi Dayanand University Interdisciplinary Life Science Programme for Advance Research and Education" for providing the necessary support and facilities for the completion of this research work. All authors would like to acknowledge the participants who contributed to this research, university staff and administration for their co-operation.

Disclosure statement

There was no potential conflict of interest reported by the authors.

Table 1. Template details used to perform homology modelling.

Additional information

Funding

The authors are highly thankful to Department of Biotechnology, Ministry of Science and Technology (DBT), Government of India for financial assistance.