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 wa...

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Veröffentlicht in:PloS one 2014-08, Vol.9 (8), p.e104544-e104544
Hauptverfasser: 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
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container_end_page e104544
container_issue 8
container_start_page e104544
container_title PloS one
container_volume 9
creator 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
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 (IC50 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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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 (IC50 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0104544</identifier><identifier>PMID: 25102000</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Analysis ; Animals ; Antiviral activity ; Antiviral Agents - chemistry ; Antiviral Agents - isolation &amp; purification ; Antiviral Agents - pharmacology ; Assaying ; Avian flu ; Biology and Life Sciences ; Calotropis gigantea ; Chromatography ; Dogs ; Embryophyta - chemistry ; Exports ; Fourier transforms ; Gene expression ; Glycosides ; Glycosides - chemistry ; Glycosides - isolation &amp; purification ; Glycosides - pharmacology ; Health aspects ; Hospitals ; Humans ; Infections ; Influenza ; Influenza A Virus, H1N1 Subtype - physiology ; Influenza viruses ; Inhibition ; Kinases ; Laboratories ; Latex ; Latex - chemistry ; Lignans - chemistry ; Lignans - isolation &amp; purification ; Lignans - pharmacology ; Madin Darby Canine Kidney Cells ; Medicine ; Metabolic pathways ; NF-κB protein ; Nuclear transport ; Orthomyxoviridae Infections - drug therapy ; Pandemics ; Phenolic compounds ; Phenols ; Physical Sciences ; Quality ; Respiratory diseases ; Ribonucleoproteins ; Science ; Sugar ; Translocation ; Viral infections ; Virus replication ; Virus Replication - drug effects ; Viruses</subject><ispartof>PloS one, 2014-08, Vol.9 (8), p.e104544-e104544</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Parhira et al. 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Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Parhira, Supawadee</au><au>Yang, Zi-Feng</au><au>Zhu, Guo-Yuan</au><au>Chen, Qiao-Lian</au><au>Zhou, Bei-Xian</au><au>Wang, Yu-Tao</au><au>Liu, Liang</au><au>Bai, Li-Ping</au><au>Jiang, Zhi-Hong</au><au>Jin, Dong-Yan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro anti-influenza virus activities of a new lignan glycoside from the latex of Calotropis gigantea</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-08-07</date><risdate>2014</risdate><volume>9</volume><issue>8</issue><spage>e104544</spage><epage>e104544</epage><pages>e104544-e104544</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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 (IC50 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25102000</pmid><doi>10.1371/journal.pone.0104544</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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1932-6203
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subjects Activation
Analysis
Animals
Antiviral activity
Antiviral Agents - chemistry
Antiviral Agents - isolation & purification
Antiviral Agents - pharmacology
Assaying
Avian flu
Biology and Life Sciences
Calotropis gigantea
Chromatography
Dogs
Embryophyta - chemistry
Exports
Fourier transforms
Gene expression
Glycosides
Glycosides - chemistry
Glycosides - isolation & purification
Glycosides - pharmacology
Health aspects
Hospitals
Humans
Infections
Influenza
Influenza A Virus, H1N1 Subtype - physiology
Influenza viruses
Inhibition
Kinases
Laboratories
Latex
Latex - chemistry
Lignans - chemistry
Lignans - isolation & purification
Lignans - pharmacology
Madin Darby Canine Kidney Cells
Medicine
Metabolic pathways
NF-κB protein
Nuclear transport
Orthomyxoviridae Infections - drug therapy
Pandemics
Phenolic compounds
Phenols
Physical Sciences
Quality
Respiratory diseases
Ribonucleoproteins
Science
Sugar
Translocation
Viral infections
Virus replication
Virus Replication - drug effects
Viruses
title In vitro anti-influenza virus activities of a new lignan glycoside from the latex of Calotropis gigantea
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