Limits...
Coadministration of Hedera helix L. Extract Enabled Mice to Overcome Insufficient Protection against Influenza A/PR/8 Virus Infection under Suboptimal Treatment with Oseltamivir.

Hong EH, Song JH, Shim A, Lee BR, Kwon BE, Song HH, Kim YJ, Chang SY, Jeong HG, Kim JG, Seo SU, Kim H, Kwon Y, Ko HJ - PLoS ONE (2015)

Bottom Line: Oral administration of ivy extract with suboptimal oseltamivir increased the antiviral activity of oseltamivir.Ivy extract and its compounds, particularly hedrasaponin F, significantly reduced the cytopathic effect in PR8-infected A549 cells in the presence of oseltamivir.Inflammatory cytokines and chemokines, including tumor necrosis factor-alpha and chemokine (C-C motif) ligand 2, were reduced by treatment with oseltamivir and the fraction of ivy extract.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, South Korea.

ABSTRACT
Several anti-influenza drugs that reduce disease manifestation exist, and although these drugs provide clinical benefits in infected patients, their efficacy is limited by the emergence of drug-resistant influenza viruses. In the current study, we assessed the therapeutic strategy of enhancing the antiviral efficacy of an existing neuraminidase inhibitor, oseltamivir, by coadministering with the leaf extract from Hedera helix L, commonly known as ivy. Ivy extract has anti-inflammatory, antibacterial, antifungal, and antihelminthic properties. In the present study, we investigated its potential antiviral properties against influenza A/PR/8 (PR8) virus in a mouse model with suboptimal oseltamivir that mimics a poor clinical response to antiviral drug treatment. Suboptimal oseltamivir resulted in insufficient protection against PR8 infection. Oral administration of ivy extract with suboptimal oseltamivir increased the antiviral activity of oseltamivir. Ivy extract and its compounds, particularly hedrasaponin F, significantly reduced the cytopathic effect in PR8-infected A549 cells in the presence of oseltamivir. Compared with oseltamivir treatment alone, coadministration of the fraction of ivy extract that contained the highest proportion of hedrasaponin F with oseltamivir decreased pulmonary inflammation in PR8-infected mice. Inflammatory cytokines and chemokines, including tumor necrosis factor-alpha and chemokine (C-C motif) ligand 2, were reduced by treatment with oseltamivir and the fraction of ivy extract. Analysis of inflammatory cell infiltration in the bronchial alveolar of PR8-infected mice revealed that CD11b+Ly6G+ and CD11b+Ly6Cint cells were recruited after virus infection; coadministration of the ivy extract fraction with oseltamivir reduced infiltration of these inflammatory cells. In a model of suboptimal oseltamivir treatment, coadministration of ivy extract fraction that includes hedrasaponin F increased protection against PR8 infection that could be explained by its antiviral and anti-inflammatory activities.

No MeSH data available.


Related in: MedlinePlus

CD11b+Ly6G+ and Ly6Gint population reduced in mice treated with the combination of oseltamivir and fraction of ivy extract.A: Absolute number of cells in BALF from PR8-infected mice treated with oseltamivir alone or oseltamivir combined with fraction 4 of ivy extract for 5 days. B: Representative plots of CD11b and Ly6G levels assessed by flow cytometry. C and E: Percentages of cell populations in B were shown as a bar graph. D and F: The number of cells calculated were shown, *P<0.05; **P<0.01; ***P<0.001 (One-way ANOVA with Tukey’s post hoc test), BALF, bronchial alveolar lavage fluid.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4476699&req=5

pone.0131089.g006: CD11b+Ly6G+ and Ly6Gint population reduced in mice treated with the combination of oseltamivir and fraction of ivy extract.A: Absolute number of cells in BALF from PR8-infected mice treated with oseltamivir alone or oseltamivir combined with fraction 4 of ivy extract for 5 days. B: Representative plots of CD11b and Ly6G levels assessed by flow cytometry. C and E: Percentages of cell populations in B were shown as a bar graph. D and F: The number of cells calculated were shown, *P<0.05; **P<0.01; ***P<0.001 (One-way ANOVA with Tukey’s post hoc test), BALF, bronchial alveolar lavage fluid.

Mentions: We analyzed cellular infiltrates in BALF following oseltamivir treatment in the presence or absence of fraction 4 to determine whether the anti-inflammatory properties of fraction 4 reduce severe inflammation, directly target influenza, or cause death following PR8 infection. We did not detect significant changes in the total BAL cells number in PR8-infected mice treated with oseltamivir and fraction 4 (Fig 6A).


Coadministration of Hedera helix L. Extract Enabled Mice to Overcome Insufficient Protection against Influenza A/PR/8 Virus Infection under Suboptimal Treatment with Oseltamivir.

Hong EH, Song JH, Shim A, Lee BR, Kwon BE, Song HH, Kim YJ, Chang SY, Jeong HG, Kim JG, Seo SU, Kim H, Kwon Y, Ko HJ - PLoS ONE (2015)

CD11b+Ly6G+ and Ly6Gint population reduced in mice treated with the combination of oseltamivir and fraction of ivy extract.A: Absolute number of cells in BALF from PR8-infected mice treated with oseltamivir alone or oseltamivir combined with fraction 4 of ivy extract for 5 days. B: Representative plots of CD11b and Ly6G levels assessed by flow cytometry. C and E: Percentages of cell populations in B were shown as a bar graph. D and F: The number of cells calculated were shown, *P<0.05; **P<0.01; ***P<0.001 (One-way ANOVA with Tukey’s post hoc test), BALF, bronchial alveolar lavage fluid.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476699&req=5

pone.0131089.g006: CD11b+Ly6G+ and Ly6Gint population reduced in mice treated with the combination of oseltamivir and fraction of ivy extract.A: Absolute number of cells in BALF from PR8-infected mice treated with oseltamivir alone or oseltamivir combined with fraction 4 of ivy extract for 5 days. B: Representative plots of CD11b and Ly6G levels assessed by flow cytometry. C and E: Percentages of cell populations in B were shown as a bar graph. D and F: The number of cells calculated were shown, *P<0.05; **P<0.01; ***P<0.001 (One-way ANOVA with Tukey’s post hoc test), BALF, bronchial alveolar lavage fluid.
Mentions: We analyzed cellular infiltrates in BALF following oseltamivir treatment in the presence or absence of fraction 4 to determine whether the anti-inflammatory properties of fraction 4 reduce severe inflammation, directly target influenza, or cause death following PR8 infection. We did not detect significant changes in the total BAL cells number in PR8-infected mice treated with oseltamivir and fraction 4 (Fig 6A).

Bottom Line: Oral administration of ivy extract with suboptimal oseltamivir increased the antiviral activity of oseltamivir.Ivy extract and its compounds, particularly hedrasaponin F, significantly reduced the cytopathic effect in PR8-infected A549 cells in the presence of oseltamivir.Inflammatory cytokines and chemokines, including tumor necrosis factor-alpha and chemokine (C-C motif) ligand 2, were reduced by treatment with oseltamivir and the fraction of ivy extract.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, South Korea.

ABSTRACT
Several anti-influenza drugs that reduce disease manifestation exist, and although these drugs provide clinical benefits in infected patients, their efficacy is limited by the emergence of drug-resistant influenza viruses. In the current study, we assessed the therapeutic strategy of enhancing the antiviral efficacy of an existing neuraminidase inhibitor, oseltamivir, by coadministering with the leaf extract from Hedera helix L, commonly known as ivy. Ivy extract has anti-inflammatory, antibacterial, antifungal, and antihelminthic properties. In the present study, we investigated its potential antiviral properties against influenza A/PR/8 (PR8) virus in a mouse model with suboptimal oseltamivir that mimics a poor clinical response to antiviral drug treatment. Suboptimal oseltamivir resulted in insufficient protection against PR8 infection. Oral administration of ivy extract with suboptimal oseltamivir increased the antiviral activity of oseltamivir. Ivy extract and its compounds, particularly hedrasaponin F, significantly reduced the cytopathic effect in PR8-infected A549 cells in the presence of oseltamivir. Compared with oseltamivir treatment alone, coadministration of the fraction of ivy extract that contained the highest proportion of hedrasaponin F with oseltamivir decreased pulmonary inflammation in PR8-infected mice. Inflammatory cytokines and chemokines, including tumor necrosis factor-alpha and chemokine (C-C motif) ligand 2, were reduced by treatment with oseltamivir and the fraction of ivy extract. Analysis of inflammatory cell infiltration in the bronchial alveolar of PR8-infected mice revealed that CD11b+Ly6G+ and CD11b+Ly6Cint cells were recruited after virus infection; coadministration of the ivy extract fraction with oseltamivir reduced infiltration of these inflammatory cells. In a model of suboptimal oseltamivir treatment, coadministration of ivy extract fraction that includes hedrasaponin F increased protection against PR8 infection that could be explained by its antiviral and anti-inflammatory activities.

No MeSH data available.


Related in: MedlinePlus