Ameliorative effects of curcumin towards cyclosporine-induced genotoxic potential: an in vitro and in silico study

Abstract

Several studies documented the ameliorative effects of curcumin which plays a pivotal role in radical scavenging activities. It also participates in various cellular pathways and interacts with multiple targets. In the present study, we investigated the ameliorative effect of curcumin upon chromosomal genotoxicity induced by cyclosporine, an immunosuppressant, using in vitro approaches. A plausible mechanism of how curcumin mitigates the genotoxic implications of cyclosporine was ascertained using in silico tools. We observed that the curcumin reduces the genotoxic consequences made by cyclosporine upon cell cycle checkpoints and associated chromosomal/DNA manifestations. In addition, we presented the mechanistic details of curcumin interaction with various biomacromolecule types using docking experiments which showed that the possible radical scavenging activities can only be emerged by inducing the expression of antioxidant enzymes, supported by available experimental evidences. We anticipate that the induction of antioxidant enzymes by curcumin would activate Nrf2-Keap1 pathway as the plausible mechanism to exert anti-inflammatory response as demonstrated in renal epithelial cells.

Keywords:

• Curcumin
• cyclosporine
• Nrf2-Keap1
• radicals
• DNA binding
• docking
• in vitro

Acknowledgements

Ankita J. Shah acknowledges financial support from Maulana Azad National Fellowship (MANF), Universiy Grants Commission (UGC), New Delhi, India as Senior Research Fellowship and Sivakumar Prasanth Kumar acknowledges support from Department of Science and Technology, New Delhi, India as INSPIRE Senior Research Fellowship (IF120266), UGC, New Delhi.

Disclosure statement

The authors report no declaration of interest.

Additional information

Funding

This work was funded by Department of Science and Technology, Government of India and University Grants Commission (UGC), New Delhi.