Active compounds of licorice ameliorate microplastics-induced intestinal damage by targeting FADD

Microplastics (MPs), as a novel type of environmental pollutant, have the potential to impact human health. This study aims to investigate the protective efficacy of active compounds in licorice on microplastics-injured rats and reveal the underlying mechanisms. The MPs-injured rat model was established by orally administrated with MPs. After the treatment with different doses of a combination of liquiritigenin, isoliquiritigenin and glycyrrhetinic acid, the tissue injury, oxidative stress, inflammation and expressions of tight junction proteins in colon and liver were evaluated. Our data showed that active compounds of licorice significantly ameliorate colonic and liver damage caused by MPs, improving function colonic barrier and liver function, reducing oxidative stress and systemic inflammatory factors. Then, a total of 29 differentially expressed proteins were identified by label-free proteomics analysis, among which the down-regulated Fas-associating protein with a novel death domain (FADD) was found to be the most related with the protective effects of licorice. What's more, this protein target also interacts directly with active compounds of licorice, through hydrogen bounds and hydrophobic interactions involving 11 residues. This study suggested that licorice exerts protective effects against MPs on rats, through down-regulating as well as directly interacting with FADD.