title: Combinations of 1,8-cineol and oseltamivir for the treatment of influenza virus A (H3N2) infection in mice.
abstract: It is need for development of new means against influenza virus due to the lack of efficacy of available therapeutic strategies. In previous research, 1,8-cineol exert its inhibition of nuclear factor (NF)-κB, the main regulator of cytokine and chemokine production in influenza, and anti-inflammatory activity. These fact supports and helps establish the hypothesis that 1,8-cineol may have synergism with an antiviral on influenza virus infection. The combined effect of 1,8-cineol with oseltamivir in a mouse type A influenza virus (Victoria/3/75,H3N2) model were examined. We initially tested combinations of 1,8-cineol (30, 60, and 120 mg/kg/day) and oseltamivir (0.1, 0.2, and 0.4 mg/kg/day). In addition, the 0.4 mg/kg/day of oseltamivir combined with 120 mg/kg of 1,8-cineol was selected for further combination studies. Oseltamivir was 30%, 40%, and 60% protective at 0.1, 0.2, and 0.4 mg/kg/d. Combinations of 1,8-cineol (30, 60, and 120 mg/kg/d) and oseltamivir (0.1, 0.2, and 0.4 mg/kg/d) increased the number of survivors and mean survival time (MST) following combination treatment was greater than monotherapy alone. Three dimensional analysis of drug interactions using the MacSynergy method showed a strong synergistic effect of these drug combinations. Survival, MST, lung parameters (lung index, viral titers, and pathology), and cytokines (IL-10, TNF-α, IL-1β, and IFN-γ) expression in lung demonstrated the high effectiveness of the combination. Combined treatment was associated with longer MST and more reduced cytokine levels than oseltamivir alone. These data demonstrate that combinations of 1,8-cineol and oseltamivir have synergistic effect against influenza A virus (H3N2) infection.
authors.affiliation: Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Yan-Ni
authors.initials: YN
authors.lastname: Lai
authors.affiliation: Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Lin-Chun
authors.initials: LC
authors.lastname: Fu
authors.affiliation: Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Liu
authors.affiliation: Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Feng-Xue
authors.initials: FX
authors.lastname: Zhang
authors.affiliation: Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Pei-Ping
authors.initials: PP
authors.lastname: Xu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000077591:Eucalyptol; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D039821:Monoterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000821:virology; D053139:Oseltamivir / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D003511:Cyclohexanols; D016207:Cytokines; D039821:Monoterpenes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D053139:Oseltamivir; D000077591:Eucalyptol
keywords: 1,8-cineol; combination therapy; influenza A (H3N2) virus; mice; oseltamivir