Eriodictyol and Diosmetin Protective Potential in Skin Infection: Antimicrobial Action, Gene and Molecular Targets, and Keratinocyte Protection Against Bacteria-Induced Damage

Abstract

Eriodictyol and diosmetin are bioactive flavonoids. This study explored their antimicrobial activities and antibiofilm potential along with the effect on pyocyanin and protease production and virulence-linked gene expression, followed by in silico molecular target predictions. Moreover, keratinocytes were used for the evaluation of cytotoxicity and protective antioxidant and anti-inflammatory effects in the infected cells. Both compounds have shown significant antibacterial capacity towards skin pathogens (minimal inhibitory concentrations 0.025–0.2 mg/mL). Their ability to prevent biofilm formation of Pseudomonas aeruginosa was drastic, as well as the impact on other virulence factors, proteases, and pyocyanin production. RT-qPCR determined downregulation of almost all genes examined (lasI, lasR, lasB, rhlI, rhlR, rhlC, pqsH, pqsR, pvdS, pvdF, phzM, and algK), while molecular docking predicted strong binding affinities to the LasI, LasR, PqsR, and QscR quorum-sensing proteins. Moreover, both compounds were not toxic to HaCaT and were able to reduce damage induced by P. aeruginosa in this cell line. Precisely, eriodictyol reduced levels of secreted IL-6 (from 335.32 to 261.76 pg), while both compounds reduced the formation of superoxide. Both eriodictyol and diosmetin displayed remarkable antimicrobial potential while employing a wide array of antimicrobial mechanisms, making them attractive candidates for further assessment and eventual incorporation into novel therapeutic strategies.