hypericum and Orthomyxoviridae-Infections

Hypericumperforatum (H. perforatum) ethanol extract has been found to inhibit lipopolysaccharide-induced production of inflammatory mediators and cytokines in cultured macrophages. Therefore, it may be able to protect the host from excessive inflammation during viral infection. In the current study, the immune-regulatory effect of H. perforatum extract was evaluated in A549 lung epithelial cells and BALB/c mice exposed to Influenza A/PR/8/34 H1N1 virus. In A549 cells, the extract (30 µg/mL) significantly inhibited influenza virus induced monocyte chemotactic protein (MCP)-1 and interferon-γ induced protein 10 kD (IP-10), but dramatically increased interleukin-6 (IL-6). In mice inoculated intranasally with 10(7.9) EID50 of Influenza A/PR/8/34 H1N1 (high dose), daily oral treatment of H. perforatum extract at a rate of 110 mg/kg of body weight increased lung viral titer, bronchoalveolar lavage (BAL) pro-inflammatory cytokine and chemokine levels, and the infiltration of pro-inflammatory cells in the lung 5 days post-inoculation, as compared to ethanol vehicle treated mice. Transcription of suppressor of cytokine signaling 3 (SOCS3) was increased by H. perforatum extract both in A549 cells and BALB/c mice, which could have interrupted anti-viral immune response and thus led to the inefficient viral clearance and increased lung inflammation. H. perforatum treatment resulted in minor reduction in viral titer without affecting body weight when mice were inoculated with a lower dose (~10(5.0) EID50) and H. perforatum was applied in the later phase of infection. Mice challenged intranasally with high dose of influenza virus (10(7.9) EID50) suffered from a higher mortality rate when dosed with H. perforatum extract. In conclusion, the current study showed that SOCS3 elevation by H. perforatum may cause impaired immune defense against influenza virus infection and lead to higher mortality.

Topics: Administration, Oral; Analysis of Variance; Animals; Blotting, Western; Bronchoalveolar Lavage Fluid; Cell Line; Chemokine CXCL10; Chemokines; Cytokines; DNA Primers; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Humans; Hypericum; Influenza A Virus, H1N1 Subtype; Interleukin-6; Mice; Mice, Inbred BALB C; Monocyte Chemoattractant Proteins; Orthomyxoviridae Infections; Plant Extracts; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins

Hypericum perforatum L., a plant used in Chinese herbal medicine, has been proven effective against many viral diseases. In the present study, the therapeutic efficacy of an extract of H. perforatum (HPE) against influenza A virus (IAV) was investigated in mice. Whether HPE would be a promising agent for influenza treatment was evaluated by measuring the protection rate, mean survival days, lung index, and viral titer, as well as the secretion of IL-6, interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), and interferon-gamma (IFN-γ) in lung tissue and serum on days 3 and 5 post-infection. The results showed that HPE could reduce the lung index and viral titer of mice infected with IAV, decrease mortality, and prolong the mean survival time. HPE decreased the concentration of IL-6 and TNF-α in lung tissue and serum on day 5 post-infection. In contrast, HPE enhanced the lung and serum levels of IL-10 and IFN-γ on the days 3 and 5 post-infection. Our study indicates that HPE has significant therapeutic efficacy for mice infected with IAV. The possible reasons for these results were concluded to be pertaining to up-regulating the expression of IL-10 and IFN-γ, and down-regulating the secretion of IL-6 and TNF-α in lung and serum.

Topics: Animals; Antiviral Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Female; Hypericum; Inflammation Mediators; Influenza A virus; Interferon-gamma; Interleukin-10; Interleukin-6; Lung; Male; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Ribavirin; Time Factors; Tumor Necrosis Factor-alpha; Viral Load

Influenza virus infects the respiratory system of human and animals causing mild to severe illness which could lead to death. Although vaccines are available, there is still a great need for influenza antiviral drugs to reduce disease progression and virus transmission. Currently two classes (M2 channel blockers and neuraminidase inhibitors) of FDA-approved influenza antiviral drugs are available, but there are great concerns of emergence of viral resistance. Therefore, timely development of new antiviral drugs against influenza viruses is crucial. Plant-derived polyphenols have been studied for antioxidant activity, anti-carcinogenic, and cardio- and neuroprotective actions. Recently, some polyphenols, such as resveratrol and epigallocatechin gallate, showed significant anti-influenza activity in vitro and/or in vivo. Therefore we investigated selected polyphenols for their antiviral activity against influenza A and B viruses. Among the polyphenols we tested, isoquercetin inhibited the replication of both influenza A and B viruses at the lowest effective concentration. In a double treatment of isoquercetin and amantadine, synergistic effects were observed on the reduction of viral replication in vitro. The serial passages of virus in the presence of isoquercetin did not lead to the emergence of resistant virus, and the addition of isoquercetin to amantadine or oseltamivir treatment suppressed the emergence of amantadine- or oseltamivir-resistant virus. In a mouse model of influenza virus infection, isoquercetin administered intraperitoneally to mice inoculated with human influenza A virus significantly decreased the virus titers and pathological changes in the lung. Our results suggest that isoquercetin may have the potential to be developed as a therapeutic agent for the treatment of influenza virus infection and for the suppression of resistance in combination therapy with existing drugs.

Topics: Amantadine; Animals; Antiviral Agents; Cell Line; Chlorocebus aethiops; Drug Evaluation, Preclinical; Drug Resistance, Viral; Drug Synergism; Equisetum; Female; Humans; Hypericum; Influenza A virus; Influenza B virus; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Oseltamivir; Plant Extracts; Quercetin; Vero Cells; Virus Replication

To investigate anti-influenza virus H3N2 effect of Hypericum japonicum in vivo.. The influences on lung index and death rate were observed in the mice infected with virus H3N2 from intranasal.. Experiments in vivo showed that Hypericum japonicum at the concentration of 10 g/kg x d for the intranasal treatment markedly inhibited the lung consolidation of mice pneumonia caused by the infection of influenza virus H3N2 and prolonged the survival time .. Hypericum japonicum may be effective on treating influenza.

Topics: Animals; Antiviral Agents; Drugs, Chinese Herbal; Female; Hypericum; Influenza A Virus, H3N2 Subtype; Lung; Male; Mice; Orthomyxoviridae Infections; Plants, Medicinal; Pneumonia, Viral; Random Allocation; Ribavirin