Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway
Background: Berberine (BBR) is an isoquinoline alkaloid which exhibits a variety of biological and therapeutic properties, and has been reported by some to block replication of the influenza virus. However, contradictory results have also been presented, and the mechanistic explanation is lacking. M...
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MDPI AG
2020-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/3/344 |
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| author | Paweł Botwina Katarzyna Owczarek Zenon Rajfur Marek Ochman Maciej Urlik Maria Nowakowska Krzysztof Szczubiałka Krzysztof Pyrc |
| author_facet | Paweł Botwina Katarzyna Owczarek Zenon Rajfur Marek Ochman Maciej Urlik Maria Nowakowska Krzysztof Szczubiałka Krzysztof Pyrc |
| author_sort | Paweł Botwina |
| collection | DOAJ |
| description | Background: Berberine (BBR) is an isoquinoline alkaloid which exhibits a variety of biological and therapeutic properties, and has been reported by some to block replication of the influenza virus. However, contradictory results have also been presented, and the mechanistic explanation is lacking. Methods: A panel of cell lines (Madin−Darby canine kidney (MDCK), adenocarcinoma human alveolar basal epithelial cells (A549), lung epithelial type I (LET1)) and primary human airway epithelial cells (HAE) susceptible to influenza virus infection were infected with a seasonal influenza A virus in the presence or absence of BBR. Cytotoxicity towards cell lines was measured using XTT assay. The yield of the virus was analyzed using RT-qPCR. To study the molecular mechanism of BBR, confocal microscopy and Western blot analyses of cellular fractions were applied. Results and conclusions: Our results show cell-type-dependent anti-influenza properties of BBR in vitro which suggests that the compound acts on the cell and not the virus. Importantly, BBR hampers influenza replication in primary human airway epithelium 3D cultures that mimic the natural replication site of the virus. Studies show that the influenza A virus upregulates the mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK) pathway and hijacks this pathway for nucleolar export of the viral ribonucleoprotein. Our results suggest that BBR interferes with this process and hampers influenza A replication. |
| first_indexed | 2024-12-11T05:53:40Z |
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| id | doaj.art-4aabc1a620234da386168a8c0f9d2cc0 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-11T05:53:40Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-4aabc1a620234da386168a8c0f9d2cc02022-12-22T01:18:45ZengMDPI AGViruses1999-49152020-03-0112334410.3390/v12030344v12030344Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK PathwayPaweł Botwina0Katarzyna Owczarek1Zenon Rajfur2Marek Ochman3Maciej Urlik4Maria Nowakowska5Krzysztof Szczubiałka6Krzysztof Pyrc7Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Krakow, PolandVirogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Krakow, PolandInstitute of Physics, Faculty of Physics, Astronomy and Applied Computer Sciences, Jagiellonian University, Lojasiewicza 11, 30-348 Krakow, PolandDepartment of Cardiac Surgery and Transplantology, Silesian Center for Heart Diseases, Marii Curie-Skłodowskiej 9, 41-800 Zabrze, PolandDepartment of Cardiac Surgery and Transplantology, Silesian Center for Heart Diseases, Marii Curie-Skłodowskiej 9, 41-800 Zabrze, PolandFaculty of Chemistry, Jagiellonian University, 30-387 Krakow, PolandFaculty of Chemistry, Jagiellonian University, 30-387 Krakow, PolandVirogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Krakow, PolandBackground: Berberine (BBR) is an isoquinoline alkaloid which exhibits a variety of biological and therapeutic properties, and has been reported by some to block replication of the influenza virus. However, contradictory results have also been presented, and the mechanistic explanation is lacking. Methods: A panel of cell lines (Madin−Darby canine kidney (MDCK), adenocarcinoma human alveolar basal epithelial cells (A549), lung epithelial type I (LET1)) and primary human airway epithelial cells (HAE) susceptible to influenza virus infection were infected with a seasonal influenza A virus in the presence or absence of BBR. Cytotoxicity towards cell lines was measured using XTT assay. The yield of the virus was analyzed using RT-qPCR. To study the molecular mechanism of BBR, confocal microscopy and Western blot analyses of cellular fractions were applied. Results and conclusions: Our results show cell-type-dependent anti-influenza properties of BBR in vitro which suggests that the compound acts on the cell and not the virus. Importantly, BBR hampers influenza replication in primary human airway epithelium 3D cultures that mimic the natural replication site of the virus. Studies show that the influenza A virus upregulates the mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK) pathway and hijacks this pathway for nucleolar export of the viral ribonucleoprotein. Our results suggest that BBR interferes with this process and hampers influenza A replication.https://www.mdpi.com/1999-4915/12/3/344influenzaberberinemapk pathway |
| spellingShingle | Paweł Botwina Katarzyna Owczarek Zenon Rajfur Marek Ochman Maciej Urlik Maria Nowakowska Krzysztof Szczubiałka Krzysztof Pyrc Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway Viruses influenza berberine mapk pathway |
| title | Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway |
| title_full | Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway |
| title_fullStr | Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway |
| title_full_unstemmed | Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway |
| title_short | Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway |
| title_sort | berberine hampers influenza a replication through inhibition of mapk erk pathway |
| topic | influenza berberine mapk pathway |
| url | https://www.mdpi.com/1999-4915/12/3/344 |
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