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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...

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Autores principales: Xu, Yinlan, Sun, Panpan, Wan, Shuangxiu, Guo, Jianhua, Zheng, Xiaozhong, Sun, Yaogui, Fan, Kuohai, Yin, Wei, Sun, Na, Li, Hongquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
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.
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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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