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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 ofH.  perforatumextract 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  EID 50  of Influenza A/PR/8/34 H1N1 (high dose), daily oral treatment ofH.  perforatumextract 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 byH.  perforatumextract 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.  perforatumtreatment resulted in minor reduction in viral titer without affecting body weight when mice were inoculated with a lower dose (~10 5.0  EID 50 ) andH.  perforatumwas applied in the later phase of infection. Mice challenged intranasally with high dose of influenza virus (10 7.9  EID 50 ) suffered from a higher mortality rate when dosed withH.  perforatumextract. In conclusion, the current study showed that SOCS3 elevation byH.  perforatummay cause impaired immune defense against influenza virus infection and lead to higher mortality.

The Immuno-Regulatory Impact of Orally-Administered Hypericum perforatum Extract on Balb/C Mice Inoculated with H1n1 Influenza A Virus