Abstract:Transmissible gastroenteritis virus (TGEV), a coronavirus that causes severe diarrhea due to oxidative stress in the piglet intestine, is a major cause of economic loss in the livestock industry. However, limited interventions have been shown to be effective in the treatment of TGEV. Here, we demonstrate the therapeutic activity of eugenol in TGEV-induced intestinal oxidative stress and apoptosis. Our data show that eugenol supplementation protects intestine and IPEC-J2 cells from TGEV-induced damage. Mechanis… Show more
“…4B). Considering the important role of TGEV-induced apoptosis in host response to TGEV infection (Wang et al 2022), the expression patterns of differentially expressed miRNAs involved in apoptosis were analyzed. Among them, the expression of miR-181 markedly reduced after PCP and TGEV infection, and the result was also confirmed by Real-time PCR ( P < 0.001) (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Due to the low efficacy, cytotoxicity, and viral resistance of synthetic antiviral drugs such as Moroxidine, Ribavirin, and Ganciclovir (Märtson et al 2022, Yu et al 2016), natural antiviral drugs are considered easy to accept because of their low toxicity and low price (Ghosh et al 2009). PCP has been proven to have pharmacological effects such as antiviral, antibacterial, anti-inflammatory, and anti-tumor effects (Wang et al 2022). Therefore, we conducted TGEV challenge on weaned piglets and then treated them with PCP.…”
Transmissible gastroenteritis virus (TGEV) is an important pathogen that can cause changes in the expression profile of cell miRNA. In this study, PCP could treat piglets infected with TGEV by in vivo experiment. High-throughput sequencing technology was used to detect that 9 miRNAs were up-regulated and 17 miRNAs were down-regulated during PCP inhibition of TGEV infection in PK15 cells. Meanwhile, miR-181 was related to the target genes of key proteins of apoptosis pathway. PK15 was treated with different PCP after transfection of miR-181 mimic or inhibitor. Real-time PCR was used to detect the effect of TGEV replication, electron microscopy, TEM and Hoechst fluorescence staining were used to detect the biological function of the treated cells, and western blot (WB) was used to detect the expression of key signaling factors cyt C, caspase 9 and P53 in the apoptotic signaling pathway. The results showed that compared with the control group, 250 μg/mL PCP significantly inhibited the replication of TGEV gRNA and gene N (P< 0.01). PK15 cells in PCP groups (250 and 125 μg/mL) had uniform cell morphology and a small number of floating cells by microscopic, no typical virus structure was observed in 250 μg/mL PCP group under TEM, and apoptosis staining showed that 250 μg/mL PCP significantly reduced the number of apoptotic cells. PCP may inhibit TGEV-induced apoptosis through Caspase-dependent mitochondrial pathway after transfection of miR-181. The above results provided a theoretical basis for further research on the mechanism of PCP anti-TGEV.
“…4B). Considering the important role of TGEV-induced apoptosis in host response to TGEV infection (Wang et al 2022), the expression patterns of differentially expressed miRNAs involved in apoptosis were analyzed. Among them, the expression of miR-181 markedly reduced after PCP and TGEV infection, and the result was also confirmed by Real-time PCR ( P < 0.001) (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Due to the low efficacy, cytotoxicity, and viral resistance of synthetic antiviral drugs such as Moroxidine, Ribavirin, and Ganciclovir (Märtson et al 2022, Yu et al 2016), natural antiviral drugs are considered easy to accept because of their low toxicity and low price (Ghosh et al 2009). PCP has been proven to have pharmacological effects such as antiviral, antibacterial, anti-inflammatory, and anti-tumor effects (Wang et al 2022). Therefore, we conducted TGEV challenge on weaned piglets and then treated them with PCP.…”
Transmissible gastroenteritis virus (TGEV) is an important pathogen that can cause changes in the expression profile of cell miRNA. In this study, PCP could treat piglets infected with TGEV by in vivo experiment. High-throughput sequencing technology was used to detect that 9 miRNAs were up-regulated and 17 miRNAs were down-regulated during PCP inhibition of TGEV infection in PK15 cells. Meanwhile, miR-181 was related to the target genes of key proteins of apoptosis pathway. PK15 was treated with different PCP after transfection of miR-181 mimic or inhibitor. Real-time PCR was used to detect the effect of TGEV replication, electron microscopy, TEM and Hoechst fluorescence staining were used to detect the biological function of the treated cells, and western blot (WB) was used to detect the expression of key signaling factors cyt C, caspase 9 and P53 in the apoptotic signaling pathway. The results showed that compared with the control group, 250 μg/mL PCP significantly inhibited the replication of TGEV gRNA and gene N (P< 0.01). PK15 cells in PCP groups (250 and 125 μg/mL) had uniform cell morphology and a small number of floating cells by microscopic, no typical virus structure was observed in 250 μg/mL PCP group under TEM, and apoptosis staining showed that 250 μg/mL PCP significantly reduced the number of apoptotic cells. PCP may inhibit TGEV-induced apoptosis through Caspase-dependent mitochondrial pathway after transfection of miR-181. The above results provided a theoretical basis for further research on the mechanism of PCP anti-TGEV.
“…This complex then binds to anti-oxidant response elements (ARE) located in the promoter region of various cytoprotective genes to promote their transcription and induce the expression of a series of cell protective genes, such as NQO1, HO-1, SOD, CAT, GSH-Px, exerting an anti-oxidative stress role [43]. Previous study had demonstrated that EUG could attenuate transmissible gastroenteritis virus-induced oxidative stress and apoptosis through the ROS-NRF2-ARE signaling pathway [23]. In this study, both in vivo and in vitro data showed that EUG activated NRF2, enhanced its nuclear translocation, and induced the expression of cytoprotective proteins NQO-1 and HO-1.…”
Section: Discussionmentioning
confidence: 99%
“…Previous study has demonstrated that EUG could reduce oxidative stress through activating the KEA1-NRF2 signaling pathway to alleviate colitis [22]. Additionally, EUG has been found to attenuate transmissible gastroenteritis virus-induced apoptosis through the ROS-NRF2-ARE signaling pathway [23]. So far, there has been no report to determine whether EUG has a protective effect on damaged pancreatic β cells in T1DM.…”
Type 1 diabetes mellitus (T1DM), known as insulin-dependent diabetes mellitus, is characterized by persistent hyperglycemia caused by damage to the pancreatic β cells and an absolute insulin deficiency, which will affect multiple organs and has a poor prognosis. Oxidative stress and apoptosis play a major role in the progression of T1DM. Eugenol (EUG) is a natural compound with anti-inflammatory, anti-oxidant, and anti-apoptosis activities. However, the potential effects of EUG on T1DM had not been investigated. In this study, we established the streptozotocin (STZ)-induced T1DM mouse modelin vivoand STZ-induced pancreatic β cell MIN6 cell modelin vitroto explore the protective effects of EUG on T1DM, and tried to illuminate the potential mechanism. Our results showed that EUG intervention could activate the expression of nuclear factor E2-related factor 2 (NRF2), increase the expressions of downstream proteins NQO-1 and HO-1 regulated by NRF2, alleviate pancreatic β cell damage in T1DM, elevate insulin secretion, and reduce the expression levels of apoptosis and oxidative stress related markers. Furthermore, these effects of EUG could be significantly reversed by ML385, an inhibitor of NRF2. The present study suggested that EUG exerted protective effects on pancreatic β cells in T1DM by mitigating apoptosis and oxidative stress through activating the NRF2 signaling pathway. Consequently, EUG holds great promise as a potential therapeutic candidate for T1DM.
“…Cleaved GSDMD forms membrane pores, leading to cytokine release and pyroptotic cell death. It has been reported that eugenol treatment inhibits apoptosis during TGEV infection . Nonetheless, we are still lacking a complete understanding of the functions of eugenol in TGEV-induced intestinal epithelial cell death, particularly in pyroptosis.…”
Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Pyroptosis is involved in the pathogenesis of coronavirus, but its role in TGEVinduced intestinal injury has yet to be fully elucidated. Eugenol, an essential plant oil, plays a vital role in antiviral innate immune responses. We demonstrate the preventive effect of eugenol on TGEV infection. Eugenol alleviates TGEV-induced intestinal epithelial cell pyroptosis and reduces intestinal injury in TGEV-infected piglets. Mechanistically, eugenol reduces the activation of NLRP3 inflammasome, thereby inhibiting TGEV-induced intestinal epithelial cell pyroptosis. In addition, eugenol scavenges TGEVinduced reactive oxygen species (ROS) increase, which in turn prevents TGEV-induced NLRP3 inflammasome activation and pyroptosis. Overall, eugenol protects the intestine by reducing TGEV-induced pyroptosis through inhibition of NLRP3 inflammasome activation, which may be mediated through intracellular ROS levels. These findings propose that eugenol may be an effective strategy to prevent TGEV infection.
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