AUTHOR=Wang Kang , Chen Daiwen , Yu Bing , He Jun , Mao Xiangbing , Huang Zhiqing , Yan Hui , Wu Aimin , Luo Yuheng , Zheng Ping , Yu Jie , Luo Junqiu 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.921613

DOI=10.3389/fimmu.2022.921613

ISSN=1664-3224

ABSTRACT=<p>Increasing evidence supports the ability of eugenol to maintain intestinal barrier integrity and anti-inflammatory <italic>in vitro</italic> and <italic>in vivo</italic>; 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 (<italic>IgG</italic>) but also significantly decreased serum inflammatory cytokine concentration (<italic>TNF-α</italic>) in TGEV-infected piglets. In addition, eugenol also significantly decreased the expression of <italic>NF-κB</italic> mRNA and the phosphorylation level of <italic>NF-κB P65</italic> 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 (<italic>ZO-1</italic>) and mRNA expression levels of nutrient transporter-related genes (<italic>GluT-2</italic> and <italic>CaT-1</italic>) 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 <italic>ZO-1</italic> and <italic>Occludin</italic> 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 <italic>ZO-1</italic> and <italic>Occludin</italic>, which may be related to the inhibition of <italic>NF-κB</italic> signaling pathway. Eugenol may offer some therapeutic opportunities for coronavirus-related diseases.</p>