Total alkaloids from Alstonia scholaris inhibit influenza a virus replication and lung immunopathology by regulating the innate immune response.

Jul 27, 2020

Contributor: Hong-Xia Zhou,Run-Feng Li,Yi-Feng Wang,Li-Han Shen,Li-Hua Cai,Yun-Ceng Weng,Huan-Rong Zhang,Xin-Xin Chen,Xiao Wu,Rui-Feng Chen,Hai-Ming Jiang,Caiyun Wang,Mingrong Yang,Jingguang Lu,Xiao-Dong Luo,Zhihong Jiang,Zi-Feng Yang

Total alkaloids from Alstonia scholaris inhibit influenza a virus replication and lung immunopathology by regulating the innate immune response.

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.

Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.

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About The Expert

Hong-Xia Zhou

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; Dongguan People’s Hospital, Dongguan, 523000, China.

Run-Feng Li

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.

Yi-Feng Wang

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.

Li-Han Shen

Dongguan People’s Hospital, Dongguan, 523000, China.

Li-Hua Cai

Dongguan People’s Hospital, Dongguan, 523000, China.

Yun-Ceng Weng

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.

Huan-Rong Zhang

Becton, Dickinson and Company, 510000, China.

Xin-Xin Chen

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.

Xiao Wu

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.

Rui-Feng Chen

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.

Hai-Ming Jiang

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.

Caiyun Wang

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.

Mingrong Yang

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.

Jingguang Lu

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China.

Xiao-Dong Luo

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. Electronic address: xdluo@mail.kib.ac.cn.

Zhihong Jiang

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000, China.

Zi-Feng Yang

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), 519020, China; KingMed Virology Diagnostic & Translational Center, 510000, China; Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, 510000, China. Electronic address: jeffyah@163.com.

References

PubMed