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J Med Virol. 2016 Dec 14. doi: 10.1002/jmv.24755. [Epub ahead of print]
Combinations of 1,8-cineol and oseltamivir for the treatment of influenza virus A (H3N2) infection in mice.
Lai YN1, Li Y1, Fu LC1, Zhao F1, Liu N1, Zhang FX1, Xu PP1.
Author information
Abstract
BACKGROUND:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSION:
These data demonstrate that combinations of 1,8-cineol and oseltamivir have synergistic effect against influenza A virus (H3N2) infection. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
1,8-cineol; Combination therapy; Influenza A (H3N2) virus; Mice; Oseltamivir
PMID: 27966790 DOI: 10.1002/jmv.24755
[PubMed - as supplied by publisher]
Combinations of 1,8-cineol and oseltamivir for the treatment of influenza virus A (H3N2) infection in mice.
Lai YN1, Li Y1, Fu LC1, Zhao F1, Liu N1, Zhang FX1, Xu PP1.
Author information
Abstract
BACKGROUND:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSION:
These data demonstrate that combinations of 1,8-cineol and oseltamivir have synergistic effect against influenza A virus (H3N2) infection. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
1,8-cineol; Combination therapy; Influenza A (H3N2) virus; Mice; Oseltamivir
PMID: 27966790 DOI: 10.1002/jmv.24755
[PubMed - as supplied by publisher]