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In Vitro Anti-Influenza Virus Activities of a New Lignan Glycoside from the Latex of Calotropis gigantea

A new lignan glycoside, (+)-pinoresinol 4-O-[6″-O-vanilloyl]-β-d-glucopyranoside (1) and two known phenolic compounds, 6′-O-vanilloyltachioside (2) and 6′-O-vanilloylisotachioside (3) were isolated from the latex of Calotropis gigantea (Asclepiadaceae). The structure of the new compound was elucidat...

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Autores principales: Parhira, Supawadee, Yang, Zi-Feng, Zhu, Guo-Yuan, Chen, Qiao-Lian, Zhou, Bei-Xian, Wang, Yu-Tao, Liu, Liang, Bai, Li-Ping, Jiang, Zhi-Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125211/
https://www.ncbi.nlm.nih.gov/pubmed/25102000
http://dx.doi.org/10.1371/journal.pone.0104544
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author Parhira, Supawadee
Yang, Zi-Feng
Zhu, Guo-Yuan
Chen, Qiao-Lian
Zhou, Bei-Xian
Wang, Yu-Tao
Liu, Liang
Bai, Li-Ping
Jiang, Zhi-Hong
author_facet Parhira, Supawadee
Yang, Zi-Feng
Zhu, Guo-Yuan
Chen, Qiao-Lian
Zhou, Bei-Xian
Wang, Yu-Tao
Liu, Liang
Bai, Li-Ping
Jiang, Zhi-Hong
author_sort Parhira, Supawadee
collection PubMed
description A new lignan glycoside, (+)-pinoresinol 4-O-[6″-O-vanilloyl]-β-d-glucopyranoside (1) and two known phenolic compounds, 6′-O-vanilloyltachioside (2) and 6′-O-vanilloylisotachioside (3) were isolated from the latex of Calotropis gigantea (Asclepiadaceae). The structure of the new compound was elucidated by using spectroscopic and chemical methods. Three isolates (1–3) and one authentic compound, (+)-pinoresinol 4-O-β-d-glucopyranoside, were screened for A/PR/8/34 (H1N1) inhibitory activity by cytopathic effect (CPE) inhibition assay on MDCK cells. Compound 1 showed inhibitory activity against A/PR/8/34 (H1N1). In sharp contrast, the other three compounds (2, 3 and (+)-pinoresinol 4-O-β-d-glucopyranoside) did not show such activity. An analysis of structure-activity relationship between 1 and (+)-pinoresinol 4-O-β-d-glucopyranoside revealed that the presence of a vanilloyl group in the sugar moiety of 1 is crucial for its anti-influenza virus activity. Compound 1 was further evaluated for in vitro inhibitory activities against a panel of human and avian influenza viruses by CPE inhibition assay. It showed inhibitory effect against human influenza viruses in both subtypes A and B (IC(50) values around 13.4–39.8 µM with SI values of 3.7–11.4), while had no effect on avian influenza viruses. Its antiviral activity against human influenza viruses subtype A was further confirmed by plaque reduction assay. The time course assay indicated that 1 exerts its antiviral activity at the early stage of viral replication. A mechanistic study showed that 1 efficiently inhibited influenza virus-induced activation of NF-κB pathway in a dose-dependent manner, but had no effect on virus-induced activation of Raf/MEK/ERK pathway. Further studies demonstrated that nuclear translocation of transcription factor NF-κB induced by influenza virus was significantly blocked by 1, meanwhile, nuclear export of viral ribonucleoproteins was also effectively inhibited. These findings suggest that this new lignan glycoside from Calotropis gigantea, may have therapeutic potential in influenza virus infection through inhibition of NF-κB pathway and viral ribonucleoproteins nuclear export.
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spelling pubmed-41252112014-08-12 In Vitro Anti-Influenza Virus Activities of a New Lignan Glycoside from the Latex of Calotropis gigantea Parhira, Supawadee Yang, Zi-Feng Zhu, Guo-Yuan Chen, Qiao-Lian Zhou, Bei-Xian Wang, Yu-Tao Liu, Liang Bai, Li-Ping Jiang, Zhi-Hong PLoS One Research Article A new lignan glycoside, (+)-pinoresinol 4-O-[6″-O-vanilloyl]-β-d-glucopyranoside (1) and two known phenolic compounds, 6′-O-vanilloyltachioside (2) and 6′-O-vanilloylisotachioside (3) were isolated from the latex of Calotropis gigantea (Asclepiadaceae). The structure of the new compound was elucidated by using spectroscopic and chemical methods. Three isolates (1–3) and one authentic compound, (+)-pinoresinol 4-O-β-d-glucopyranoside, were screened for A/PR/8/34 (H1N1) inhibitory activity by cytopathic effect (CPE) inhibition assay on MDCK cells. Compound 1 showed inhibitory activity against A/PR/8/34 (H1N1). In sharp contrast, the other three compounds (2, 3 and (+)-pinoresinol 4-O-β-d-glucopyranoside) did not show such activity. An analysis of structure-activity relationship between 1 and (+)-pinoresinol 4-O-β-d-glucopyranoside revealed that the presence of a vanilloyl group in the sugar moiety of 1 is crucial for its anti-influenza virus activity. Compound 1 was further evaluated for in vitro inhibitory activities against a panel of human and avian influenza viruses by CPE inhibition assay. It showed inhibitory effect against human influenza viruses in both subtypes A and B (IC(50) values around 13.4–39.8 µM with SI values of 3.7–11.4), while had no effect on avian influenza viruses. Its antiviral activity against human influenza viruses subtype A was further confirmed by plaque reduction assay. The time course assay indicated that 1 exerts its antiviral activity at the early stage of viral replication. A mechanistic study showed that 1 efficiently inhibited influenza virus-induced activation of NF-κB pathway in a dose-dependent manner, but had no effect on virus-induced activation of Raf/MEK/ERK pathway. Further studies demonstrated that nuclear translocation of transcription factor NF-κB induced by influenza virus was significantly blocked by 1, meanwhile, nuclear export of viral ribonucleoproteins was also effectively inhibited. These findings suggest that this new lignan glycoside from Calotropis gigantea, may have therapeutic potential in influenza virus infection through inhibition of NF-κB pathway and viral ribonucleoproteins nuclear export. Public Library of Science 2014-08-07 /pmc/articles/PMC4125211/ /pubmed/25102000 http://dx.doi.org/10.1371/journal.pone.0104544 Text en © 2014 Parhira et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Parhira, Supawadee
Yang, Zi-Feng
Zhu, Guo-Yuan
Chen, Qiao-Lian
Zhou, Bei-Xian
Wang, Yu-Tao
Liu, Liang
Bai, Li-Ping
Jiang, Zhi-Hong
In Vitro Anti-Influenza Virus Activities of a New Lignan Glycoside from the Latex of Calotropis gigantea
title In Vitro Anti-Influenza Virus Activities of a New Lignan Glycoside from the Latex of Calotropis gigantea
title_full In Vitro Anti-Influenza Virus Activities of a New Lignan Glycoside from the Latex of Calotropis gigantea
title_fullStr In Vitro Anti-Influenza Virus Activities of a New Lignan Glycoside from the Latex of Calotropis gigantea
title_full_unstemmed In Vitro Anti-Influenza Virus Activities of a New Lignan Glycoside from the Latex of Calotropis gigantea
title_short In Vitro Anti-Influenza Virus Activities of a New Lignan Glycoside from the Latex of Calotropis gigantea
title_sort in vitro anti-influenza virus activities of a new lignan glycoside from the latex of calotropis gigantea
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125211/
https://www.ncbi.nlm.nih.gov/pubmed/25102000
http://dx.doi.org/10.1371/journal.pone.0104544
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