Ameliorative effects of curcumin towards cyclosporine-induced genotoxic potential: anin vitroandin silicostudy

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.

The Cytoprotective Activity of Nrf2 Is Regulated by Phytochemicals (Sulforaphane, Curcumin, and Silymarin)

“…This could imply a mechanism through the cancer and the inflammatory regulator activity of curcumin [177]. Recently, some research studies demonstrated the putative interaction of curcumin derivatives on the core of Keap1 or directly on Nrf2 [178]. Additionally, the molecular docking results of some 4-quinolinyn chalcones exhibited that a structurally related small molecule is well-situated by the bound region of Keap1-Kelch and NrF2 through stable hydrogen bonds and the hydrophobic interaction (in a way similar to that depicted in Fig.…”