PMID- 37889426 OWN - NLM STAT- MEDLINE DCOM- 20240408 LR - 20240408 IS - 1573-7446 (Electronic) IS - 0165-7380 (Linking) VI - 48 IP - 2 DP - 2024 Apr TI - Glycyrrhizin alleviates varicellovirus bovinealpha 1-induced oxidative stress, inflammation, and apoptosis in MDBK cells by inhibiting NF-kappaB/NLRP3 axis through the Nrf2 signalling pathway. PG - 749-759 LID - 10.1007/s11259-023-10242-7 [doi] AB - 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)-1beta, IL-8, tumor necrosis factor (TNF)-alpha, phosphorylated NF-kappaB p65 (p-NF-kappaB 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-kappaB inhibitor) treated MDBK cells, IL-1beta, IL-8, TNF-alpha, p-NF-kappaB 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-kappaB/NLRP3 axis. In addition, after BoAHV-1 infection, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and p-NF-kappaB 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-kappaB 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-kappaB 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-kappaB/NLRP3 axis. CI - (c) 2023. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Guo, Bing AU - Guo B AD - Key Laboratory of Healthy Breeding in dairy cattle (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei Province, China. AD - Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, Hebei Province, China. FAU - Wang, Haifeng AU - Wang H AD - Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, Hebei Province, China. FAU - Zhang, Yue AU - Zhang Y AD - Key Laboratory of Healthy Breeding in dairy cattle (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei Province, China. FAU - Wang, Chuanwen AU - Wang C AD - Key Laboratory of Healthy Breeding in dairy cattle (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei Province, China. FAU - Qin, Jianhua AU - Qin J AD - Key Laboratory of Healthy Breeding in dairy cattle (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei Province, China. qjhqqq@126.com. LA - eng PT - Journal Article DEP - 20231027 PL - Switzerland TA - Vet Res Commun JT - Veterinary research communications JID - 8100520 RN - 0 (NF-kappa B) RN - 0 (BAY 11-7085) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 6FO62043WK (Glycyrrhizic Acid) RN - 0 (NF-E2-Related Factor 2) RN - EC 3.4.22.- (Caspase 3) RN - 0 (Reactive Oxygen Species) RN - 0 (Interleukin-8) RN - 0 (Antioxidants) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Nitriles) RN - 0 (Sulfones) SB - IM MH - Animals MH - Cattle MH - *NF-kappa B/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Glycyrrhizic Acid/pharmacology/therapeutic use MH - NF-E2-Related Factor 2/metabolism/pharmacology MH - Caspase 3/metabolism/pharmacology/therapeutic use MH - Reactive Oxygen Species/metabolism/pharmacology/therapeutic use MH - Interleukin-8/therapeutic use MH - Oxidative Stress MH - Inflammation/drug therapy/veterinary/metabolism MH - Antioxidants/pharmacology MH - Apoptosis MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Tumor Necrosis Factor-alpha/metabolism MH - *Cattle Diseases MH - *Nitriles MH - *Sulfones OTO - NOTNLM OT - Varicellovirus Bovinealpha 1 OT - Apoptosis OT - Glycyrrhizin OT - Inflammation OT - Oxidative stress EDAT- 2023/10/27 12:44 MHDA- 2024/04/08 06:42 CRDT- 2023/10/27 11:13 PHST- 2023/06/10 00:00 [received] PHST- 2023/10/11 00:00 [accepted] PHST- 2024/04/08 06:42 [medline] PHST- 2023/10/27 12:44 [pubmed] PHST- 2023/10/27 11:13 [entrez] AID - 10.1007/s11259-023-10242-7 [pii] AID - 10.1007/s11259-023-10242-7 [doi] PST - ppublish SO - Vet Res Commun. 2024 Apr;48(2):749-759. doi: 10.1007/s11259-023-10242-7. Epub 2023 Oct 27.