title: The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function.
abstract: BACKGROUND
  Lianhuaqingwen Capsule (LH-C) is a traditional Chinese medicine (TCM) formula used to treat respiratory tract infectious diseases in Chinese. The aim of this study was to determine the antiviral activity of LH-C and its immunomodulatory effects on viral infection.
  
  
  METHODS
  The in vitro cytotoxicity and antiviral activity of LH-C was determined by MTT and Plaque reduction assays. Time course study under single-cycle virus growth conditions were used to determine which stage of viral replication was blocked. The effect of LH-C on the nuclear export of the viral nucleoprotein was examined using an indirect immunofluorescence assay. The regulation to different signaling transduction events and cytokine/chemokine expression of LH-C was evaluated using Western blotting and real-time RT-PCR. After virus inoculation, BALB/c mice were administered with LH-C of different concentrations for 5 days. Body-weight, viral titers and lung pathology of the mice were measured, the level of inflammatory cytokines were also examined using real-time RT-PCR.
  
  
  RESULTS
  LH-C inhibited the proliferation of influenza viruses of various strain in vitro, with the 50% inhibitory concentration (IC50) ranging from 0.35 to 2 mg/mL. LH-C blocked the early stages (0-2 h) of virus infection, it also suppressed virus-induced NF-kB activation and alleviated virus-induced gene expression of IL-6, IL-8, TNF-a, IP-10, and MCP-1 in a dose-dependent manner. LH-C treatment efficiently impaired the nuclear export of the viral RNP. A decrease of the viral titers in the lungs of mice were observed in groups administered with LH-C. The level of inflammatory cytokines were also decreased in the early stages of infection.
  
  
  CONCLUSIONS
  LH-C, as a TCM prescription, exerts broad-spectrum effects on a series of influenza viruses, including the newly emerged H7N9, and particularly regulates the immune response of virus infection. Thus, LH-C might be a promising option for treating influenza virus infection.
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, National Center for clinical research, The First Affiliated Hospital, Guangzhou Medical University, 1 Kangda Road, Guangzhou, 510230, China.|Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, 12 Airport Road, Guangzhou, 510405, China.
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, National Center for clinical research, The First Affiliated Hospital, Guangzhou Medical University, 1 Kangda Road, Guangzhou, 510230, China.|Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, 12 Airport Road, Guangzhou, 510405, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, National Center for clinical research, The First Affiliated Hospital, Guangzhou Medical University, 1 Kangda Road, Guangzhou, 510230, China.
authors.forename: Runfeng
authors.initials: R
authors.lastname: Li
authors.affiliation: Otolaryngological Department, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, National Center for clinical research, The First Affiliated Hospital, Guangzhou Medical University, 1 Kangda Road, Guangzhou, 510230, China.|Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida da Universidade, Taipa, Macau SAR, 999078, China.
authors.forename: Beixian
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, National Center for clinical research, The First Affiliated Hospital, Guangzhou Medical University, 1 Kangda Road, Guangzhou, 510230, China.
authors.forename: Qiaolian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Science department, University of British Columbia, 2329 West Mall, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Pui Leng
authors.initials: PL
authors.lastname: Cheng
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, National Center for clinical research, The First Affiliated Hospital, Guangzhou Medical University, 1 Kangda Road, Guangzhou, 510230, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Yutao
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, National Center for clinical research, The First Affiliated Hospital, Guangzhou Medical University, 1 Kangda Road, Guangzhou, 510230, China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases, National Center for clinical research, The First Affiliated Hospital, Guangzhou Medical University, 1 Kangda Road, Guangzhou, 510230, China. jeffyah@163.com.|Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida da Universidade, Taipa, Macau SAR, 999078, China. jeffyah@163.com.
authors.forename: Zifeng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, 12 Airport Road, Guangzhou, 510405, China. zhangfengxue@gzucm.edu.cn.
authors.forename: Fengxue
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008168:Lung / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D016328:NF-kappa B / Q000378:metabolism; D019590:Nucleocapsid Proteins / Q000378:metabolism; D009975:Orthomyxoviridae / Q000187:drug effects*; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D008517:Phytotherapy; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D019590:Nucleocapsid Proteins; C000588632:lianhuaqingwen
keywords: Antiviral; Immuno-regulation; Influenza virus; Lianhuaqingwen capsule