Total alkaloids from Alstonia scholaris inhibit influenza a virus replication and lung immunopathology by regulating the innate immune response.
A549 Cells
Alkaloids
/ chemistry
Alstonia
/ chemistry
Animals
Anti-Inflammatory Agents, Non-Steroidal
/ chemistry
Antiviral Agents
/ chemistry
Cytokines
/ metabolism
Dogs
Female
Humans
Immunity, Innate
/ drug effects
Influenza A Virus, H1N1 Subtype
/ drug effects
Influenza, Human
/ drug therapy
Lung
/ drug effects
Madin Darby Canine Kidney Cells
Mice, Inbred C57BL
Orthomyxoviridae Infections
/ drug therapy
Virus Replication
/ drug effects
Acute lung injury
Alstonia scholaris
Anti-inflammatory
Innate immune response
Total alkaloids
influenza a virus
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
12
02
2020
revised:
01
06
2020
accepted:
28
06
2020
pubmed:
24
7
2020
medline:
9
1
2021
entrez:
24
7
2020
Statut:
ppublish
Résumé
Alstonia scholaris is a folk medicine used to treat cough, asthma and chronic obstructive pulmonary disease in China. Total alkaloids (TA) from A. scholaris exhibit anti-inflammatory properties in acute respiratory disease, which suggests their possible anti-inflammatory effect on influenza virus infection. To assess the clinical use of TA by demonstrating their anti-influenza and anti-inflammatory effects and the possible mechanism underlying the effect of TA on influenza A virus (IAV) infection in vitro and to reveal the inhibitory effect of TA on lung immunopathology caused by IAV infection. Antiviral and anti-inflammatory activities were assessed in Madin-Darby canine kidney (MDCK) and A549 cells and U937-derived macrophages infected with influenza A/PR/8/34 (H1N1) virus. Proinflammatory cytokine levels were measured by real-time quantitative PCR and Bio-Plex assays. The activation of innate immune signaling induced by H1N1 virus in the absence or presence of TA was detected in A549 cells by Western blot. Furthermore, mice were infected intranasally with H1N1 virus and treated with TA (50, 25 and 12.5 mg/kg/d) or oseltamivir (60 mg/kg/d) for 5 days in vivo. The survival rates and body weight were recorded, and the viral titer, proinflammatory cytokine levels, innate immune cell populations and histopathological changes in the lungs were analyzed. TA significantly inhibited viral replication in A549 cells and U937-derived macrophages and markedly reduced cytokine and chemokine production at the mRNA and protein levels. Furthermore, TA blocked the activation of pattern recognition receptor (PRR)- and IFN-activated signal transduction in A549 cells. Critically, TA also increased the survival rate, reduced the viral titer, suppressed proinflammatory cytokine production and innate immune cell infiltration and improved lung histopathology in a lethal PR8 mouse model. TA exhibits anti-viral and anti-inflammatory effects against IAV infection by interfering with PRR- and IFN-activated signal transduction.
Sections du résumé
BACKGROUND
BACKGROUND
Alstonia scholaris is a folk medicine used to treat cough, asthma and chronic obstructive pulmonary disease in China. Total alkaloids (TA) from A. scholaris exhibit anti-inflammatory properties in acute respiratory disease, which suggests their possible anti-inflammatory effect on influenza virus infection.
PURPOSE
OBJECTIVE
To assess the clinical use of TA by demonstrating their anti-influenza and anti-inflammatory effects and the possible mechanism underlying the effect of TA on influenza A virus (IAV) infection in vitro and to reveal the inhibitory effect of TA on lung immunopathology caused by IAV infection.
METHODS
METHODS
Antiviral and anti-inflammatory activities were assessed in Madin-Darby canine kidney (MDCK) and A549 cells and U937-derived macrophages infected with influenza A/PR/8/34 (H1N1) virus. Proinflammatory cytokine levels were measured by real-time quantitative PCR and Bio-Plex assays. The activation of innate immune signaling induced by H1N1 virus in the absence or presence of TA was detected in A549 cells by Western blot. Furthermore, mice were infected intranasally with H1N1 virus and treated with TA (50, 25 and 12.5 mg/kg/d) or oseltamivir (60 mg/kg/d) for 5 days in vivo. The survival rates and body weight were recorded, and the viral titer, proinflammatory cytokine levels, innate immune cell populations and histopathological changes in the lungs were analyzed.
RESULTS
RESULTS
TA significantly inhibited viral replication in A549 cells and U937-derived macrophages and markedly reduced cytokine and chemokine production at the mRNA and protein levels. Furthermore, TA blocked the activation of pattern recognition receptor (PRR)- and IFN-activated signal transduction in A549 cells. Critically, TA also increased the survival rate, reduced the viral titer, suppressed proinflammatory cytokine production and innate immune cell infiltration and improved lung histopathology in a lethal PR8 mouse model.
CONCLUSION
CONCLUSIONS
TA exhibits anti-viral and anti-inflammatory effects against IAV infection by interfering with PRR- and IFN-activated signal transduction.
Identifiants
pubmed: 32702592
pii: S0944-7113(20)30103-3
doi: 10.1016/j.phymed.2020.153272
pii:
doi:
Substances chimiques
Alkaloids
0
Anti-Inflammatory Agents, Non-Steroidal
0
Antiviral Agents
0
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153272Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None