title: 14-Deoxy-11,12-didehydroandrographolide attenuates excessive inflammatory responses and protects mice lethally challenged with highly pathogenic A(H5N1) influenza viruses.
abstract: Traditional Chinese medicine (TCM) has been an excellent treasury for centuries' accumulation of clinical experiences, which deserves to be tapped for potential drugs and improved using modern scientific methods. 14-Deoxy-11,12-didehydroandrographolide (DAP), a major component of an important TCM named Andrographis paniculata, with non-toxic concentration of 1000 mg/kg/day, effectively reduced the mortality and weight loss of mice lethally challenged with A/chicken/Hubei/327/2004 (H5N1) or A/PR/8/34 (H1N1) influenza A viruses (IAV) when initiated at 4 h before infection, or A/duck/Hubei/XN/2007 (H5N1) when initiated at 4 h or 48 h before infection, or 4 h post-infection (pi). DAP (1000 or 500 mg/kg/day) also significantly diminished lung virus titres of infected mice when initiated at 4 h or 48 h before infection, or 4 h pi. In the infection of A/duck/Hubei/XN/2007 (H5N1), DAP (1000 mg/kg/day) treatment initiated at 48 h before infection gained the best efficacy that virus titres in lungs of mice in log10TCID50/mL reduced from 2.61 ± 0.14 on 3 days post-infection (dpi), 2.98 ± 0.17 on 5 dpi, 3.54 ± 0.19 on 7 dpi to 1.46 ± 0.14 on 3 dpi, 1.86 ± 0.18 on 5 dpi, 2.03 ± 0.21 on 7 dpi. Moreover, DAP obviously alleviated lung histopathology and also strongly inhibited proinflammatory cytokines/chemokines expression. The mRNA levels of TNF-α, IL-1β, IL-6, CCL-2/MCP-1, IFN-α, IFN-β, IFN-γ, MIP-1α, MIP-1β in lungs of A/duck/Hubei/XN/2007 (H5N1)-infected mice and serum protein expression of TNF-α, IL-1β, IL-6, CCL-2/MCP-1 and CXCL-10/IP-10 in mice infected with all the three strains of IAV were all significantly reduced by DAP. Results demonstrated that DAP could restrain both the host intense inflammatory responses and high viral load, which were considered to contribute to the pathogenesis of H5N1 virus and should be controlled together in a clinical setting. Considering the anti-inflammatory and anti-IAV activities of DAP, DAP may be a promising active component obtained from A. paniculata, which can be further investigated as a useful constitute of curative strategies in the future against IAV, the H5N1 strains in particular.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, College of Life Sciences, Hubei University, Wuhan 430062, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Sunrui
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Anding
authors.initials: A
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: jml8328@126.com.
authors.forename: Meilin
authors.initials: M
authors.lastname: Jin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001835:Body Weight; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000472:pathogenicity; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000473:pathology* / Q000821:virology*; D019562:Viral Load
chemical_list: C495626:14-deoxy-11,12-didehydroandrographolide; D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D016207:Cytokines; D004224:Diterpenes; D018836:Inflammation Mediators
keywords: 14-Deoxy-11,12-didehydroandrographolide; Andrographis paniculata; Anti-inflammatory; Antiviral; H5N1; Traditional Chinese medicine