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The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2
BACKGROUND: Porcine circovirus type 2 (PCV2) is an important and common DNA virus that infect pig and can cause immunosuppression and induce apoptosis in the infected cells. To escape the host immune system, PCV2 constantly builds up complex mechanisms or mutates genes, and that is why it is difficu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549248/ https://www.ncbi.nlm.nih.gov/pubmed/33046006 http://dx.doi.org/10.1186/s12866-020-01986-2 |
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author | Xu, Yinlan Sun, Panpan Wan, Shuangxiu Guo, Jianhua Zheng, Xiaozhong Sun, Yaogui Fan, Kuohai Yin, Wei Sun, Na Li, Hongquan |
author_facet | Xu, Yinlan Sun, Panpan Wan, Shuangxiu Guo, Jianhua Zheng, Xiaozhong Sun, Yaogui Fan, Kuohai Yin, Wei Sun, Na Li, Hongquan |
author_sort | Xu, Yinlan |
collection | PubMed |
description | BACKGROUND: Porcine circovirus type 2 (PCV2) is an important and common DNA virus that infect pig and can cause immunosuppression and induce apoptosis in the infected cells. To escape the host immune system, PCV2 constantly builds up complex mechanisms or mutates genes, and that is why it is difficult to eradicate complex PCV2 infection by relying on vaccines and single compound. At present, there is few literature reports on the effective prevention and treatment of PCV2 infection by a combination of two or more compounds. Previously, we have demonstrated the anti-PCV2 effect of Matrine in vitro, but its mechanism has not been further evaluated. Literatures have proven that Osthole has a variety of pharmacological activities, and we tested the ability of Osthole to inhibit PCV2 replication in cell culture. Therefore, this study explored the synergistic antiviral effect of Matrine combined with Osthole and their synergistic anti-apoptotic mechanism. RESULTS: Osthole alone had an anti-PCV2 effect, and then its synergistic anti-PCV2 effect of Osthole and Matrine was better than that of Matrine or Osthole alone as demonstrated by qRT-PCR, IFA and Western blotting results. The anti-apoptotic mechanism of these two compounds by inducing the PERK pathway by PCV2 was elucidated through Annexin V-FITC/PI, JC-1 and Western blotting. Matrine and Osthole combination could inhibit the expression of Cap in Cap-transfected PK-15 cells, thus inhibiting Cap-induced PERK apoptosis. Ribavirin was used as a positive control. CONCLUSIONS: The combination of Osthole and Matrine had the synergistic effect of anti-PCV2 infection by directly inhibiting the expression of PCV2 Cap protein. The combination of these two compounds also inhibited PERK apoptosis induced by PCV2 Cap protein, possibly by regulating the level of GRP78. The results formed a base for further studies on the mechanism of anti-PCV2 in vivo using Matrine and Osthole combination and developing new anti-PCV2 compounds with Cap and GRP78 as therapeutic targets. |
format | Online Article Text |
id | pubmed-7549248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-75492482020-10-13 The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2 Xu, Yinlan Sun, Panpan Wan, Shuangxiu Guo, Jianhua Zheng, Xiaozhong Sun, Yaogui Fan, Kuohai Yin, Wei Sun, Na Li, Hongquan BMC Microbiol Research Article BACKGROUND: Porcine circovirus type 2 (PCV2) is an important and common DNA virus that infect pig and can cause immunosuppression and induce apoptosis in the infected cells. To escape the host immune system, PCV2 constantly builds up complex mechanisms or mutates genes, and that is why it is difficult to eradicate complex PCV2 infection by relying on vaccines and single compound. At present, there is few literature reports on the effective prevention and treatment of PCV2 infection by a combination of two or more compounds. Previously, we have demonstrated the anti-PCV2 effect of Matrine in vitro, but its mechanism has not been further evaluated. Literatures have proven that Osthole has a variety of pharmacological activities, and we tested the ability of Osthole to inhibit PCV2 replication in cell culture. Therefore, this study explored the synergistic antiviral effect of Matrine combined with Osthole and their synergistic anti-apoptotic mechanism. RESULTS: Osthole alone had an anti-PCV2 effect, and then its synergistic anti-PCV2 effect of Osthole and Matrine was better than that of Matrine or Osthole alone as demonstrated by qRT-PCR, IFA and Western blotting results. The anti-apoptotic mechanism of these two compounds by inducing the PERK pathway by PCV2 was elucidated through Annexin V-FITC/PI, JC-1 and Western blotting. Matrine and Osthole combination could inhibit the expression of Cap in Cap-transfected PK-15 cells, thus inhibiting Cap-induced PERK apoptosis. Ribavirin was used as a positive control. CONCLUSIONS: The combination of Osthole and Matrine had the synergistic effect of anti-PCV2 infection by directly inhibiting the expression of PCV2 Cap protein. The combination of these two compounds also inhibited PERK apoptosis induced by PCV2 Cap protein, possibly by regulating the level of GRP78. The results formed a base for further studies on the mechanism of anti-PCV2 in vivo using Matrine and Osthole combination and developing new anti-PCV2 compounds with Cap and GRP78 as therapeutic targets. BioMed Central 2020-10-12 /pmc/articles/PMC7549248/ /pubmed/33046006 http://dx.doi.org/10.1186/s12866-020-01986-2 Text en © The Author(s) 2020 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/. The Creative Commons Public Domain Dedication waiver (http://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 Xu, Yinlan Sun, Panpan Wan, Shuangxiu Guo, Jianhua Zheng, Xiaozhong Sun, Yaogui Fan, Kuohai Yin, Wei Sun, Na Li, Hongquan The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2 |
title | The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2 |
title_full | The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2 |
title_fullStr | The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2 |
title_full_unstemmed | The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2 |
title_short | The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2 |
title_sort | combined usage of matrine and osthole inhibited endoplasmic reticulum apoptosis induced by pcv2 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549248/ https://www.ncbi.nlm.nih.gov/pubmed/33046006 http://dx.doi.org/10.1186/s12866-020-01986-2 |
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