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Polyprenols and influenza infections (preclinical)

Preclinical study.

The study was conducted in the laboratory conditions with the use of mice. The polyprenolic preparation showed pronounced protective properties – the animals receiving polyprenols came through the infection much easier. The results suggest that polyprenols are involved in the generation of interferon, in the suppression of synthesis of viral proteins and restoration of membrane functions of cells. Taking into consideration the efficacy and low toxicity of polyprenolic preparations, they can be recommended in the clinic for the prevention of influenza, in the complex treatment, as well as in the therapy of immunity deficiency states of the body.

Sukhinin V.P.,
Sultanov V.S.,
Zarubaev V.V.,
Roshchin V.I.,
Nikitina T.V.,
Vedernikov D.N.3
Research Institute of Influenza of the Russian Academy of Medical Sciences, Saint Petersburg, Russia
Solagran Limited, Melbourne, Australia S.M. Kirov Academy of Forestry Engineering in Saint Petersburg, Saint Petersburg, Russia
I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint Petersburg, Russia

Introduction

Suppression of synthesis of viral proteins is the main mechanism of antiviral action of interferon (IFN). It is known that modification of viral proteins using prenylation is an important regulatory and pathogenetic mechanism ensuring the interaction between virion with the surface of the cell and the release of daughter viral particles. Thus, prenylation inhibitors are a promising means of control of viral infections.

Study Purpose

Study of protective activity of the plant polyprenolic preparation (PP) and its modified analog (MAP) on the model of lethal influenza infection in white mice.

Methods

The animals were infected with the adapted virus of influenza A/Aichi/2/68 (H3N2). PP and MAP were introduced in compliance with the prevention scheme, one time, 2 days before being infected with the virus of influenza A. Three doses of the virus were used in infecting — 1, 0.2 and 0.1 Sh50 (Ш50). The mortality rate of animals was registered within 14 days after being infected, the protection index of the preparations was calculated on the basis of the received data. The induction of IFN in the blood serum was studied by using the biological method. Pathological changes in the organs of the animals were studied using the histological analysis.

Results

PP and MAP in cases of one-time introduction 2 days before the intranasal infecting of the mice with the virus of influenza A/Aichi/2/68 (H3N2) demonstrated pronounced protective properties. Their protective effect was manifested in the reliable decrease of the mortality rate (by 8-47% depending on the dose of the virus and preparation), as well as the increase of the life period of the animals compared to the group receiving placebo. In addition, there was a sharp reduction in the number of influenza pneumonia foci in the lungs of the animals, identified using the histological analysis. It was shown that the mechanism of the protective action of polyprenols is associated with the stimulation of generation of macrophages (under the influence of PP - 3.5 times, under the influence of MAP - 2.4 times) and the suppression of the neutrophilic reaction at the early stages of infection. These phenomena, in their turn, were due to the induction of IFN in the blood serum of animals. It is shown that the nature of induction of IFN by polyprenols differs fundamentally from the induction using cycloferon. In cases of oral introduction, the studied preparations showed the synthesis of IFN that was higher both in terms of the level and duration. The interferon inducing effect of preparations in cases of oral introduction was higher than the effect of cycloferon, and in cases of intraperitoneal introduction was lower within the 1st day of action. Thus, cycloferon induced the generation of IFN within up to 3 days in cases of oral and intraperitoneal introduction, with the maximum effect being achieved within the 1st day, after which its effect declined sharply. At the same time, PP induced the generation of IFN within 5 days: the maximum effect in cases of oral introduction was observed on the 1st day, after which the level of IFN declined slightly (by 20%) and remained high throughout 5 days. In cases of intraperitoneal introduction of PP, the maximum values of IFN were achieved on the 3rd day, and the effect of the preparation persisted on the 5th day.

Conclusions

The results of the studies suggest that polyprenols in the body in cases of viral infection take part in the suppression of synthesis of viral proteins and restoration of membrane functions of a cell due to the glycosylation of the protein bonds. Thus, taking into account the effectiveness of the polyprenolic preparation and its modified analog, as well as their low toxicity, it is possible to recommend them in the clinic for the prevention of influenza, in its complex treatment, as well as in the therapy of immunodeficiency states of the organism. (Published in the proceedings of the International Conference "Development of Scientific Research and Surveillance of Infectious Diseases"/ edited by A.B. Zhebrun. — SPb.: Louis Pasteur Research Institute of Epidemiology and Microbiology in Saint Petersburg, Federal Budgetary Institution of Science of Rospotrebnadzor (Federal Service for Supervision of Consumer Rights Protection and Human Well-Being), 2010)


The text of the study is provided by courtesy of Solagran.