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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

TIC chromatograms of chromatography fractions.The HSF content of each fraction analyzed using a chromatogram. HSF, hederasaponin F; TIC, total ion current.
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pone.0131089.g003: TIC chromatograms of chromatography fractions.The HSF content of each fraction analyzed using a chromatogram. HSF, hederasaponin F; TIC, total ion current.

Mentions: To develop drug candidates for combined anti-influenza therapy with oseltamivir, we set out to find the fraction of ivy extract that predominantly contains HSF. Fig 3 shows the HSF content of each fraction. We confirmed that HSF was present in fractions 3, 4, and 5. Using fractionation of ivy extract with column chromatography and mass spectrometry analysis, we showed that the highest percentage of HSF was contained in the 60% MeOH fraction of ivy extract (fraction 4). Therefore, we selected fraction 4 for further experiments.


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)

TIC chromatograms of chromatography fractions.The HSF content of each fraction analyzed using a chromatogram. HSF, hederasaponin F; TIC, total ion current.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131089.g003: TIC chromatograms of chromatography fractions.The HSF content of each fraction analyzed using a chromatogram. HSF, hederasaponin F; TIC, total ion current.
Mentions: To develop drug candidates for combined anti-influenza therapy with oseltamivir, we set out to find the fraction of ivy extract that predominantly contains HSF. Fig 3 shows the HSF content of each fraction. We confirmed that HSF was present in fractions 3, 4, and 5. Using fractionation of ivy extract with column chromatography and mass spectrometry analysis, we showed that the highest percentage of HSF was contained in the 60% MeOH fraction of ivy extract (fraction 4). Therefore, we selected fraction 4 for further experiments.

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