Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway

• Published in: Frontiers in immunology Vol. 13; p. 921613
• Main Authors: Wang, Kang, Chen, Daiwen, Yu, Bing, He, Jun, Mao, Xiangbing, Huang, Zhiqing, Yan, Hui, Wu, Aimin, Luo, Yuheng, Zheng, Ping, Yu, Jie, Luo, Junqiu
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 16.08.2022
• Subjects: eugenol; immunity; Immunology; intestinal epithelial barrier; intestinal inflammation; transmissible gastroenteritis virus; weaned pigs
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.921613

Increasing evidence supports the ability of eugenol to maintain intestinal barrier integrity and anti-inflammatory in vitro and in vivo ; however, whether eugenol alleviates virus-mediated intestinal barrier damage and inflammation remains a mystery. Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Here, we found that eugenol could alleviate TGEV-induced intestinal functional impairment and inflammatory responses in piglets. Our results indicated that eugenol improved feed efficiency in TGEV-infected piglets. Eugenol not only increased serum immunoglobulin concentration ( IgG ) but also significantly decreased serum inflammatory cytokine concentration ( TNF-α ) in TGEV-infected piglets. In addition, eugenol also significantly decreased the expression of NF-κB mRNA and the phosphorylation level of NF-κB P65 protein in the jejunum mucosa of TGEV-infected piglets. Eugenol increased villus height and the ratio of villus height to crypt depth in the jejunum and ileum, and decreased serum D-lactic acid levels. Importantly, eugenol increased tight junction protein ( ZO-1 ) and mRNA expression levels of nutrient transporter-related genes ( GluT-2 and CaT-1 ) in the jejunum mucosa of TGEV-infected piglets. Meanwhile, compared with TGEV-infected IPEC-J2 cells, treatment with eugenol reduced the cell cytopathic effect, attenuated the inflammatory response. Interestingly, eugenol did not increase the expression of ZO-1 and Occludin in IPEC-J2 cells. However, western blot and immunofluorescence results showed that eugenol restored TGEV-induced down-regulation of ZO-1 and Occludin, while BAY11-7082 (The NF-κB specific inhibitor) enhanced the regulatory ability of eugenol. Our findings demonstrated that eugenol attenuated TGEV-induced intestinal injury by increasing the expression of ZO-1 and Occludin , which may be related to the inhibition of NF-κB signaling pathway. Eugenol may offer some therapeutic opportunities for coronavirus-related diseases.