Exploration of molecular interactions between scoparone and associated compounds with Constitutive androstane receptor (CAR) leading to gallstone prevention: an in silico investigation

Abstract

Scoparone (6, 7 dimethylesculetin) is a biologically active compound derived from the herb Artemisia capillaris having anti-inflammatory, anti-lipemic, and anti-allergic roles. Activation of the constitutive androstane receptor (CAR) in primary hepatocytes of both wild-type and humanized CAR mice by scoparone, accelerates bilirubin and cholesterol clearance in vivo. This can prevent gallstones which is a dreaded gastrointestinal disease. To date, surgery is regarded as the gold standard for treating gallstones. The molecular interactions between scoparone and CAR leading to gallstone prevention are not yet explored. In this study, we have analyzed these interactions through an insilico approach. After extracting the CAR structures (mice and human) from the protein databank and 6, 7-dimethylesuletin from PubChem, energy minimization of both the receptors was done to make them stable followed by docking. Next, a simulation was performed to stabilize the docked complexes. Through docking, H-bonds and pi-pi interactions were found in the complexes, which imply a stable interaction, thus activating the CAR. A similarity search for scoparone was performed and the selected compounds were docked with the CAR receptors. Esculentin acetate and scopoletin acetate interacted with human CAR through pi-alkyl and H-bond respectively. While Fraxidin methyl ether, fraxinol methyl ether, and 6, 7 diethoxycoumarin interacted with mice CAR through H-bond and Pi-Pi T-shaped bonds. The selected complexes were simulated further. Our results are in accordance with the hypothesis in the literature. We have also analyzed the drug likeliness, absorption, non-carcinogenicity, and other properties of scoparone which can support further in vivo studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• Constitutive androstane receptor (CAR)
• cholesterol gallstones
• pigment gallstones
• Artemisia capillaris
• 6
• 7-dimethylesculetin

Acknowledgements

The authors acknowledge Bioinformatics lab, department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi for providing the Lab facilities. Bhavna Sharma acknowledges Birla Institute of Technology for providing Institute Research fellowship (GO/Estb/Ph.D/IRF/2019-20/6649). The authors would also like to acknowledge Vivek Chandra Mohan for his valuable guidance.

Authors’ contribution statement

Bhavna Sharma has contributed to the plan and conception of the work, and performance of docking and simulation studies. Dr. Shubha Rani Sharma has contributed towards compiling the various previous researches and their results as well as the present and future researches that are being planned and executed for the prevention of gallstones. Dr. Raju Poddar and Dr. Amit Prasad have given their inputs on various Bioinformatics steps followed in the in-silico study of CAR with the 6,7-dimethylesculetin. Bhavya Sethi and Shashank Kumar have initiated the bioinformatics approach for the interaction of Human and Mice CAR with the 6,7-dimethylesculetin. All authors approve of the final version of the manuscript.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

The authors report there are no competing interests to declare.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.