Geniposide demonstrates anti-inflammatory and antiviral activity against pandemic A/Jiangsu/1/2009 (H1N1) influenza virus infection in vitro and in vivo

Background: Influenza A viruses (IAVs) have been a great threat to human health for centuries, without effective control. Geniposide, a main iridoid glycoside compound extracted from Gardenia jasminoides Ellis fruit, possesses various biological activities including anti-inflammation and anti-virus. Methods: Madin-Darby canine kidney (MDCK) cells were infected with pandemic A/Jiangsu/1/2009 (H1N1) influenza virus in vitro. Cytotoxicity and antiviral activity of geniposide were estimated by MTT assay. The influenza respiratory tract infection murine model was established by intranasal instillation of pandemic A/Jiangsu/1/2009 (H1N1) influenza virus. One day after infection, the mice were administered with geniposide (5, 10 or 20 mg/kg/day) or the neuraminidase inhibitor (NAI) peramivir (30 mg/kg/day). Body weight, survival time, viral titre and lung index of the mice were measured. The sandwich enzyme-linked immunosorbent assay (ELISA) was used to examine levels of inflammatory cytokines. Results: The data showed that geniposide had little cytotoxicity on MDCK cells and protected them from pandemic A/Jiangsu/1/2009 (H1N1) influenza virus-induced cell injury. In the infected mice, geniposide treatment significantly restored the body weights, decreased the mortality, alleviated viral titres and virus-induced lung lesions. Geniposide substantially inhibited the virus-induced alveolar wall changes, alveolar haemorrhage and neutrophil-infiltration in lung tissues. Levels of inflammatory mediators, including tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-6 and IL-10 were also markedly altered after treatment with geniposide. Conclusions: Our investigation suggested that geniposide effectively inhibited cell damage mediated by pandemic A/Jiangsu/1/2009 (H1N1) influenza virus and mitigated virus-induced acute inflammation.