Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway
The pathogenesis of many viral infections lies on the damage caused by the immune response against the virus. Current antiviral drugs do not act on the inflammatory component of the disease. Thus, new compounds that inhibit both viral multiplication and the immunopathology elicited by the virus are...
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2015
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008584_v204_n5_p575_Bueno http://hdl.handle.net/20.500.12110/paper_03008584_v204_n5_p575_Bueno |
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paper:paper_03008584_v204_n5_p575_Bueno2023-06-08T15:27:33Z Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway Antiviral Carnosic acid ERK pathway HSV-1 Immunomodulatory Jatropholones carnosic acid carnosic acid derivative diterpenoid immunoglobulin enhancer binding protein interleukin 6 jatropholone jatropholone A jatropholone B mitogen activated protein kinase toll like receptor toll like receptor 2 toll like receptor 4 toll like receptor 9 toll like receptor agonist tumor necrosis factor alpha unclassified drug antivirus agent cytokine diterpene immunosuppressive agent animal cell antiviral activity Article controlled study cytokine production cytokine release disease course drug activity drug effect drug structure Herpes simplex virus 1 immunomodulatory activity inflammation macrophage activation macrophage culture nonhuman priority journal signal transduction Vero cell line virus inhibition virus strain animal antagonists and inhibitors cell line Chlorocebus aethiops drug effects immunology mouse physiology signal transduction virus replication Animals Antiviral Agents Cell Line Cercopithecus aethiops Cytokines Diterpenes Herpesvirus 1, Human Immunosuppressive Agents MAP Kinase Signaling System Mice Virus Replication The pathogenesis of many viral infections lies on the damage caused by the immune response against the virus. Current antiviral drugs do not act on the inflammatory component of the disease. Thus, new compounds that inhibit both viral multiplication and the immunopathology elicited by the virus are an approach that should be considered. In the present study, we identified two jatropholones (2A and 5B) and one carnosic acid derivative (9C) that significantly inhibited multiplication of TK+ and TK− strains of HSV-1 in Vero cells. Compounds 2A, 5B and 9C also prevented HSV-1- and TLRs-induced inflammatory response in cultivated murine macrophages. In macrophages infected with HSV-1, the inhibitory effect of compounds 2A, 5B and 9C on TNF-α and IL-6 production could be associated with the block of ERK pathway, whereas NF-κB pathway was not hampered by any of the compounds. Besides, 2A, 5B and 9C also inhibited ERK pathway and reduced TNF-α production in macrophages stimulated with TLR2, TLR4 or TLR9 agonists and were able to hinder IL-6 secretion after activation with TLR2 or TLR4, but not with TLR9. The immunomodulatory effect of 2A, 5B and 9C in macrophages infected with HSV-1 may be a consequence of the inhibition of ERK pathway activated by TLRs. The availability of compounds with both antiviral and immunomodulatory properties which affect TLR signaling pathways might be a useful strategy to control the progress of virus-induced disease. © 2014, Springer-Verlag Berlin Heidelberg. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008584_v204_n5_p575_Bueno http://hdl.handle.net/20.500.12110/paper_03008584_v204_n5_p575_Bueno |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Antiviral Carnosic acid ERK pathway HSV-1 Immunomodulatory Jatropholones carnosic acid carnosic acid derivative diterpenoid immunoglobulin enhancer binding protein interleukin 6 jatropholone jatropholone A jatropholone B mitogen activated protein kinase toll like receptor toll like receptor 2 toll like receptor 4 toll like receptor 9 toll like receptor agonist tumor necrosis factor alpha unclassified drug antivirus agent cytokine diterpene immunosuppressive agent animal cell antiviral activity Article controlled study cytokine production cytokine release disease course drug activity drug effect drug structure Herpes simplex virus 1 immunomodulatory activity inflammation macrophage activation macrophage culture nonhuman priority journal signal transduction Vero cell line virus inhibition virus strain animal antagonists and inhibitors cell line Chlorocebus aethiops drug effects immunology mouse physiology signal transduction virus replication Animals Antiviral Agents Cell Line Cercopithecus aethiops Cytokines Diterpenes Herpesvirus 1, Human Immunosuppressive Agents MAP Kinase Signaling System Mice Virus Replication |
| spellingShingle |
Antiviral Carnosic acid ERK pathway HSV-1 Immunomodulatory Jatropholones carnosic acid carnosic acid derivative diterpenoid immunoglobulin enhancer binding protein interleukin 6 jatropholone jatropholone A jatropholone B mitogen activated protein kinase toll like receptor toll like receptor 2 toll like receptor 4 toll like receptor 9 toll like receptor agonist tumor necrosis factor alpha unclassified drug antivirus agent cytokine diterpene immunosuppressive agent animal cell antiviral activity Article controlled study cytokine production cytokine release disease course drug activity drug effect drug structure Herpes simplex virus 1 immunomodulatory activity inflammation macrophage activation macrophage culture nonhuman priority journal signal transduction Vero cell line virus inhibition virus strain animal antagonists and inhibitors cell line Chlorocebus aethiops drug effects immunology mouse physiology signal transduction virus replication Animals Antiviral Agents Cell Line Cercopithecus aethiops Cytokines Diterpenes Herpesvirus 1, Human Immunosuppressive Agents MAP Kinase Signaling System Mice Virus Replication Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway |
| topic_facet |
Antiviral Carnosic acid ERK pathway HSV-1 Immunomodulatory Jatropholones carnosic acid carnosic acid derivative diterpenoid immunoglobulin enhancer binding protein interleukin 6 jatropholone jatropholone A jatropholone B mitogen activated protein kinase toll like receptor toll like receptor 2 toll like receptor 4 toll like receptor 9 toll like receptor agonist tumor necrosis factor alpha unclassified drug antivirus agent cytokine diterpene immunosuppressive agent animal cell antiviral activity Article controlled study cytokine production cytokine release disease course drug activity drug effect drug structure Herpes simplex virus 1 immunomodulatory activity inflammation macrophage activation macrophage culture nonhuman priority journal signal transduction Vero cell line virus inhibition virus strain animal antagonists and inhibitors cell line Chlorocebus aethiops drug effects immunology mouse physiology signal transduction virus replication Animals Antiviral Agents Cell Line Cercopithecus aethiops Cytokines Diterpenes Herpesvirus 1, Human Immunosuppressive Agents MAP Kinase Signaling System Mice Virus Replication |
| description |
The pathogenesis of many viral infections lies on the damage caused by the immune response against the virus. Current antiviral drugs do not act on the inflammatory component of the disease. Thus, new compounds that inhibit both viral multiplication and the immunopathology elicited by the virus are an approach that should be considered. In the present study, we identified two jatropholones (2A and 5B) and one carnosic acid derivative (9C) that significantly inhibited multiplication of TK+ and TK− strains of HSV-1 in Vero cells. Compounds 2A, 5B and 9C also prevented HSV-1- and TLRs-induced inflammatory response in cultivated murine macrophages. In macrophages infected with HSV-1, the inhibitory effect of compounds 2A, 5B and 9C on TNF-α and IL-6 production could be associated with the block of ERK pathway, whereas NF-κB pathway was not hampered by any of the compounds. Besides, 2A, 5B and 9C also inhibited ERK pathway and reduced TNF-α production in macrophages stimulated with TLR2, TLR4 or TLR9 agonists and were able to hinder IL-6 secretion after activation with TLR2 or TLR4, but not with TLR9. The immunomodulatory effect of 2A, 5B and 9C in macrophages infected with HSV-1 may be a consequence of the inhibition of ERK pathway activated by TLRs. The availability of compounds with both antiviral and immunomodulatory properties which affect TLR signaling pathways might be a useful strategy to control the progress of virus-induced disease. © 2014, Springer-Verlag Berlin Heidelberg. |
| title |
Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway |
| title_short |
Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway |
| title_full |
Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway |
| title_fullStr |
Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway |
| title_full_unstemmed |
Natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the ERK signaling pathway |
| title_sort |
natural and semisynthetic diterpenoids with antiviral and immunomodulatory activities block the erk signaling pathway |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008584_v204_n5_p575_Bueno http://hdl.handle.net/20.500.12110/paper_03008584_v204_n5_p575_Bueno |
| _version_ |
1768544365068681216 |