The mechanism of Esculetin inhibiting Infectious Bronchitis Virus replication by Regulating Infectious Bronchitis Virus-induced expression of β-interferon and related cytokines

AbstractInfectious bronchitis virus could negatively regulate interferon pathway.Esculetinas the active ingredient inFraxini Cortexhas the effect of inhibiting infectious bronchitis, but its therapeutic mechanism is unknown. Therefore, this study aimed to investigate molecular mechanism of the inhibition of IBV replication byEsculetin. MTT assay was used to determine the cytotoxicity and the inhibitory effect ofEsculetinon IBV proliferation. Real time PCR was used to detect the changes of IBV genomic vector in trachea, lung, intestine, liver, kidney and muscle tissues of the embryo body before and after usingEsculetin.Real time PCR and Western blotting were used to detect the copy number of IBV genome and the effect of IBV on the expression level of related cytokines in the β-interferon signaling pathway before and after treatment withEsculetin. The results suggest thatEsculetinhad a significant inhibitory effect on IBV replication. 10mg/mlEsculetinhad the weakest inhibitory effect on cell proliferation and the weakest toxicity. IBV could be detected in all tissues and organs of the embryo body, and the highest virus content was found in lung and trachea tissues .Esculetincan promote the expression of important cytokines in IBV-induced host cell β-interferon signaling pathway and reduce the inhibitory of the expression of MDA5, IFN-β and Mx in the early stage of IBV infection effect, regulate the antagonism of IBV against host cell β-interferon signaling pathway. This study shows thatEsculetincan promote the natural immunity of host cells to achieve antiviral effect. It provided a theoretical basis for theEsculetinto be used as a therapeutic drug for IBV.