Naringenin inhibits PRV replication by regulating the TLR4/NF-κB pathway mediated inflammatory response

Pseudorabies is an acute and highly contagious disease caused by the pseudorabies virus (PRV). PRV has a wide range of host susceptibilities and has caused significant economic losses to the global swine industry. Currently, no specific drugs for the treatment or prevention of PRV are known. Therefore, safe and effective anti-PRV drugs are urgently needed. We extensively screened monomeric compounds and ultimately found that the flavonoid compound naringenin exhibited potent anti-PRV activity. The experimental results revealed that naringenin inhibited PRV proliferation in PK-15 cells in a dose-dependent manner. The effects of naringenin on the TLR4/NF-κB pathway were detected at the gene and protein levels. The results demonstrated that PRV infection triggered activation of the NF-κB signaling pathway, whereas naringenin exerted anti-inflammatory effects through multiple mechanisms. Specifically, naringenin suppressed the expression of TLR4 and P65 proteins, thereby inhibiting NF-κB pathway activation. This intervention subsequently attenuated the expression levels of pro-inflammatory mediators (IL-18, IL-1β, TNF-α, and IL-6) and reduced nuclear translocation of the P65 protein. All the mice in the PRV infection group died during the experimental period, whereas the survival rate of the mice in the medium-dose naringenin group (100 mg/kg) reached 57.14 %. Naringenin at high, medium, and low doses significantly inhibited the replication of PRV in the brain, lungs, and kidneys of the mice and alleviated the pathological changes induced by PRV infection. These data suggest that naringenin has potent anti-PRV activity, which provides a novel strategy for the prevention and control of PRV.