Glycyrrhizin alleviates varicellovirus bovinealpha 1-induced oxidative stress, inflammation, and apoptosis in MDBK cells by inhibiting NF-κB/NLRP3 axis through the Nrf2 signalling pathway

Varicellovirus bovinealpha 1 (BoAHV-1) is one of the crucial pathogens of bovine respiratory diseases, and its pathogenic mechanism involves oxidative stress, inflammation response, and apoptosis. Glycyrrhizin (GLY) possesses powerful antiviral, antioxidant, anti-inflammatory, and anti-apoptotic bioactivities. However, the anti-BoAHV-1 activity of GLY and its role in BoAHV-1-induced oxidative stress, inflammation, and apoptosis remain unclear. Therefore, the current study investigated the anti-BoAHV-1 effect of GLY and its ability to alleviate BoAHV-1-induced oxidative stress, inflammation, and apoptosis using an in vitro model (MDBK cells). Our results showed that BoAHV-1 titers significantly increased in MDBK cells after infection, and GLY reduced the BoAHV-1 titers in MDBK cells exposed to it. Furthermore, Interleukin (IL)-1 beta, IL-8, tumor necrosis factor (TNF)-alpha, phosphorylated NF-kappa B p65 (p-NF-kappa B p65), the NLR pyrin domain containing 3 (NLRP3), Caspase-1, and Cleaved Caspase-3 levels were significantly upregulated when MDBK cells were challenged with BoAHV-1. In BAY 11-7085 (a specific NF-kappa B inhibitor) treated MDBK cells, IL-1 beta, IL-8, TNF-alpha, p-NF-kappa B p65, NLRP3, Caspase-1, and Cleaved Caspase-3 levels were downregulated. Notably, GLY treatment had the same trend as the BAY 11-7085 treatment. Thus, these results suggested that GLY exerted anti-inflammatory and anti-apoptotic activities by blocking NF-kappa B/NLRP3 axis. In addition, after BoAHV-1 infection, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and p-NF-kappa B p65 and apoptosis rate were increased, and catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities, as well as NF-E2-related nuclear factor erythroid-2 (Nrf2) protein expression were repressed. Compared with BoAHV-1-infected MDBK cells, GLY treatment significantly downregulated intracellular ROS, MDA, and p-NF-kappa B p65 levels and apoptotic rates and significantly increased intracellular CAT and GSH-Px enzyme activities and Nrf2 expression. Additionally, ML385 (a specific Nrf2 inhibitor) abolished the enhancing effect of GLY on Nrf2 and the attenuating effect on ROS, p-NF-kappa B p65, and apoptosis. These results suggested that GLY had an anti-BoAHV-1 effect and could mitigate BoAHV-1-induced oxidative stress, inflammation, and apoptosis by activating the Nrf2 signalling and restraining NF-kappa B/NLRP3 axis.

Automated summary

The study found that glycyrrhizin (GLY) has anti-Varicellovirus bovinealpha 1 (BoAHV-1) activity, and it can alleviate BoAHV-1-induced oxidative stress, inflammation, and apoptosis by activating the Nrf2 signaling pathway and inhibiting the NF-kappa B/NLRP3 axis.