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Curcumol inhibits encephalomyocarditis virus by promoting IFN-β secretion

BACKGROUND: Encephalomyocarditis virus (EMCV) infection can cause reproductive failure in sows and acute myocarditis and sudden death in piglets. It has caused huge economic losses to the global pig industry and that is why it is necessary to develop effective new treatment compounds. Zedoary turmer...

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Autores principales: Zheng, Jiangang, Xu, Yinlan, Khan, Ajab, Sun, Panpan, Sun, Yaogui, Fan, Kuohai, Yin, Wei, Wang, Shaoyu, Li, Hongquan, Sun, Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482695/
https://www.ncbi.nlm.nih.gov/pubmed/34587973
http://dx.doi.org/10.1186/s12917-021-03015-4
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author Zheng, Jiangang
Xu, Yinlan
Khan, Ajab
Sun, Panpan
Sun, Yaogui
Fan, Kuohai
Yin, Wei
Wang, Shaoyu
Li, Hongquan
Sun, Na
author_facet Zheng, Jiangang
Xu, Yinlan
Khan, Ajab
Sun, Panpan
Sun, Yaogui
Fan, Kuohai
Yin, Wei
Wang, Shaoyu
Li, Hongquan
Sun, Na
author_sort Zheng, Jiangang
collection PubMed
description BACKGROUND: Encephalomyocarditis virus (EMCV) infection can cause reproductive failure in sows and acute myocarditis and sudden death in piglets. It has caused huge economic losses to the global pig industry and that is why it is necessary to develop effective new treatment compounds. Zedoary turmeric oil has been used for treating myocarditis. Curcumol extracted from the roots of curcuma is one of the main active ingredient of zedoary turmeric oil. The anti-EMCV activity of curcumol along with the molecular mechanisms involved with a focus on IFN-β signaling pathway was investigated in this study. METHOD: 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the maximum non-toxic concentration (MNTC), 50% cytotoxic concentration (CC(50)), maximum inhibition rate (MIR) and 50% effective concentration (EC(50)) against EMCV. Through EMCV load, the anti-viral effect of curcumol was quantitatively determined using real-time quantitative PCR (qPCR). The effect of curcumol on the expression of IFN-β was investigated using real-time quantitative PCR and ELISA. Western blot was used to determine the amounts of MDA5, MAVS, TANK, IRF3 and P-IRF3 proteins in human embryonic kidney 293 T (HEK-293 T) cells infected with EMCV. RESULTS: The results of MTT showed that compared with the ribavirin positive control group, the maximum inhibition ratio (MIR) of curcumol was greater but the selection index (SI) value was much smaller than that of ribavirin. The results of qPCR showed that curcumol and ribavirin significantly reduced the replication of EMCV in HEK-293 T cells. The curcumol (0.025 mg/mL) treatment has significantly increased IFN-β mRNA expression in the EMCV-infected HEK-293 T cells while ribavirin treatment did not. The results of ELISA showed that curcumol (0.025 mg/mL and 0.0125 mg/mL) has significantly increased the expression of IFN-β protein in EMCV-infected HEK-293 T cells. The results of Western blot showed that curcumol can inhibit the degradation of TANK protein mediated by EMCV and promote the expression of MDA5 and P-IRF3, while the protein expression level of MAVS and IRF3 remain unchanged. CONCLUSION: Curcumol has biological activity against EMCV which we suggest that IFN-β signaling pathway is one of its mechanisms. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-021-03015-4.
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spelling pubmed-84826952021-10-04 Curcumol inhibits encephalomyocarditis virus by promoting IFN-β secretion Zheng, Jiangang Xu, Yinlan Khan, Ajab Sun, Panpan Sun, Yaogui Fan, Kuohai Yin, Wei Wang, Shaoyu Li, Hongquan Sun, Na BMC Vet Res Research Article BACKGROUND: Encephalomyocarditis virus (EMCV) infection can cause reproductive failure in sows and acute myocarditis and sudden death in piglets. It has caused huge economic losses to the global pig industry and that is why it is necessary to develop effective new treatment compounds. Zedoary turmeric oil has been used for treating myocarditis. Curcumol extracted from the roots of curcuma is one of the main active ingredient of zedoary turmeric oil. The anti-EMCV activity of curcumol along with the molecular mechanisms involved with a focus on IFN-β signaling pathway was investigated in this study. METHOD: 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the maximum non-toxic concentration (MNTC), 50% cytotoxic concentration (CC(50)), maximum inhibition rate (MIR) and 50% effective concentration (EC(50)) against EMCV. Through EMCV load, the anti-viral effect of curcumol was quantitatively determined using real-time quantitative PCR (qPCR). The effect of curcumol on the expression of IFN-β was investigated using real-time quantitative PCR and ELISA. Western blot was used to determine the amounts of MDA5, MAVS, TANK, IRF3 and P-IRF3 proteins in human embryonic kidney 293 T (HEK-293 T) cells infected with EMCV. RESULTS: The results of MTT showed that compared with the ribavirin positive control group, the maximum inhibition ratio (MIR) of curcumol was greater but the selection index (SI) value was much smaller than that of ribavirin. The results of qPCR showed that curcumol and ribavirin significantly reduced the replication of EMCV in HEK-293 T cells. The curcumol (0.025 mg/mL) treatment has significantly increased IFN-β mRNA expression in the EMCV-infected HEK-293 T cells while ribavirin treatment did not. The results of ELISA showed that curcumol (0.025 mg/mL and 0.0125 mg/mL) has significantly increased the expression of IFN-β protein in EMCV-infected HEK-293 T cells. The results of Western blot showed that curcumol can inhibit the degradation of TANK protein mediated by EMCV and promote the expression of MDA5 and P-IRF3, while the protein expression level of MAVS and IRF3 remain unchanged. CONCLUSION: Curcumol has biological activity against EMCV which we suggest that IFN-β signaling pathway is one of its mechanisms. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-021-03015-4. BioMed Central 2021-09-30 /pmc/articles/PMC8482695/ /pubmed/34587973 http://dx.doi.org/10.1186/s12917-021-03015-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Zheng, Jiangang
Xu, Yinlan
Khan, Ajab
Sun, Panpan
Sun, Yaogui
Fan, Kuohai
Yin, Wei
Wang, Shaoyu
Li, Hongquan
Sun, Na
Curcumol inhibits encephalomyocarditis virus by promoting IFN-β secretion
title Curcumol inhibits encephalomyocarditis virus by promoting IFN-β secretion
title_full Curcumol inhibits encephalomyocarditis virus by promoting IFN-β secretion
title_fullStr Curcumol inhibits encephalomyocarditis virus by promoting IFN-β secretion
title_full_unstemmed Curcumol inhibits encephalomyocarditis virus by promoting IFN-β secretion
title_short Curcumol inhibits encephalomyocarditis virus by promoting IFN-β secretion
title_sort curcumol inhibits encephalomyocarditis virus by promoting ifn-β secretion
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482695/
https://www.ncbi.nlm.nih.gov/pubmed/34587973
http://dx.doi.org/10.1186/s12917-021-03015-4
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