Insights into the direct anti-influenza virus mode of action of Rhodiola rosea.

Acute respiratory infection Influenza Natural product Prodelphinidin gallate oligomers Resistance Roseroot

Journal

Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794

Informations de publication

Date de publication:
Feb 2022
Historique:
received: 23 08 2021
revised: 24 11 2021
accepted: 11 12 2021
pubmed: 14 1 2022
medline: 27 1 2022
entrez: 13 1 2022
Statut: ppublish

Résumé

The anti-influenza A virus activities and contents of previously isolated most active flavonoids (rhodiosin and tricin) from a standardized hydro-ethanolic R. rosea root and rhizome extract (SHR-5®), did not fully explain the efficacy of SHR-5®. Moreover, the mode of antiviral action of SHR-5® is unknown. To determine the anti-influenza viral principle of SHR-5® we evaluated i) the combined anti-influenza virus effect of rhodiosin and tricin, ii) the impact of its tannin-enriched fraction (TE), iii) its antiviral spectrum and mode of action, and iv) its propensity for resistance development in vitro. The combined anti-influenza virus effect of rhodiosin and tricin and the impact of TE were investigated with cytopathic effect (CPE)-inhibition assays in MDCK cells. A tannin-depleted fraction (TD) and TE were prepared by polyamide column chromatography and dereplicated by LC-MS. Plaque-reduction assays provided insights into the anti-influenza virus profile, the mode of action, and the propensity for resistance development of SHR-5®. Our results i) did not reveal synergistic anti-influenza A virus effects of rhodiosin and tricin, but ii) proved a strong impact of TE mainly composed of prodelphinidin gallate oligomers. iii) TE inhibited the plaque-production of influenza virus A(H1N1)pdm09, A(H3N2), and B (Victoria and Yamagata) isolates (including isolates resistant to neuraminidase and/or M2 ion channel inhibitors) with 50% inhibitory concentration values between 0.12 - 0.53 µg/ml similar to SHR-5®. Mechanistic studies proved a virucidal activity, inhibition of viral adsorption, viral neuraminidase activity, and virus spread by SHR-5® and TE. iv) No resistance development was observed in vitro. For the first time a comprehensive analysis of the anti-influenza virus profile of a hydro-ethanolic R. rosea extract (SHR-5®) was assessed in vitro. The results demonstrating broad-spectrum multiple direct anti-influenza virus activities, and a lack of resistance development to SHR-5® together with its known augmentation of host defense, support its potential role as an adaptogen against influenza virus infection.

Sections du résumé

BACKGROUND BACKGROUND
The anti-influenza A virus activities and contents of previously isolated most active flavonoids (rhodiosin and tricin) from a standardized hydro-ethanolic R. rosea root and rhizome extract (SHR-5®), did not fully explain the efficacy of SHR-5®. Moreover, the mode of antiviral action of SHR-5® is unknown.
PURPOSE OBJECTIVE
To determine the anti-influenza viral principle of SHR-5® we evaluated i) the combined anti-influenza virus effect of rhodiosin and tricin, ii) the impact of its tannin-enriched fraction (TE), iii) its antiviral spectrum and mode of action, and iv) its propensity for resistance development in vitro.
METHODS METHODS
The combined anti-influenza virus effect of rhodiosin and tricin and the impact of TE were investigated with cytopathic effect (CPE)-inhibition assays in MDCK cells. A tannin-depleted fraction (TD) and TE were prepared by polyamide column chromatography and dereplicated by LC-MS. Plaque-reduction assays provided insights into the anti-influenza virus profile, the mode of action, and the propensity for resistance development of SHR-5®.
RESULTS RESULTS
Our results i) did not reveal synergistic anti-influenza A virus effects of rhodiosin and tricin, but ii) proved a strong impact of TE mainly composed of prodelphinidin gallate oligomers. iii) TE inhibited the plaque-production of influenza virus A(H1N1)pdm09, A(H3N2), and B (Victoria and Yamagata) isolates (including isolates resistant to neuraminidase and/or M2 ion channel inhibitors) with 50% inhibitory concentration values between 0.12 - 0.53 µg/ml similar to SHR-5®. Mechanistic studies proved a virucidal activity, inhibition of viral adsorption, viral neuraminidase activity, and virus spread by SHR-5® and TE. iv) No resistance development was observed in vitro.
CONCLUSION CONCLUSIONS
For the first time a comprehensive analysis of the anti-influenza virus profile of a hydro-ethanolic R. rosea extract (SHR-5®) was assessed in vitro. The results demonstrating broad-spectrum multiple direct anti-influenza virus activities, and a lack of resistance development to SHR-5® together with its known augmentation of host defense, support its potential role as an adaptogen against influenza virus infection.

Identifiants

pubmed: 35026524
pii: S0944-7113(21)00435-9
doi: 10.1016/j.phymed.2021.153895
pii:
doi:

Substances chimiques

Antiviral Agents 0
Neuraminidase EC 3.2.1.18

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

153895

Informations de copyright

Copyright © 2021. Published by Elsevier GmbH.

Auteurs

Kristin Döring (K)

Section of Experimental Virology, Department of Medical Microbiology, Jena University Hospital, Hans-Knöll-Str. 2, d-07745 Jena, Germany.

Julia Langeder (J)

Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria.

Susanne Duwe (S)

Robert Koch Institute, Unit 17: Influenza and Other Respiratory Viruses, National Reference Centre for Influenza, Seestr. 10, d-13353 Berlin, Germany.

Ammar Tahir (A)

Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria.

Ulrike Grienke (U)

Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria.

Judith M Rollinger (JM)

Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria. Electronic address: judith.rollinger@univie.ac.at.

Michaela Schmidtke (M)

Section of Experimental Virology, Department of Medical Microbiology, Jena University Hospital, Hans-Knöll-Str. 2, d-07745 Jena, Germany. Electronic address: michaela.schmidtke@med.uni-jena.de.

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Classifications MeSH