Effects and Mechanisms of Silibinin on Influenza A/H1N1 Pathogenesis in a Mouse Model.

Abstract

Silymarin is a polyphenolic flavonoid extracted from milk thistle. It has potent immunomodulatory effects and can inhibit the replication of influenza A virus (IAV). The present study aimed to determine the inflammatory and anti-inflammatory cytokine secretion patterns in mice before and after silibinin treatment. For this, bronchoalveolar lavage (BAL) fluids were collected from the thoracic cavity 5 days after the intervention, and viral quantification was performed using TaqMan Real-time PCR. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate IFN-γ and IL-10 levels in serum and BAL samples. Finally, pathological damage to lung tissue was assessed by pathologists. The results reveal that silibinin pretreatment exhibits a dose-dependent immunomodulatory effect on IFN-γ and IL-10 levels. After the virus challenge, silibinin reduced immune cell infiltration in mouse BAL fluid. These data similarly suggest a remarkable immunomodulatory effect of silibinin. Silibinin also decreased lung damage following the virus challenge in the post-treatment group, but its lung protective properties seem to be due to a different mechanism than when it was administered before infection. Finally, high doses of silibinin (post-treatment) significantly reduced viral load in BAL fluid compared to the virus challenge group. These results support the idea that therapies aimed at moderating immune and inflammatory responses are essential to decrease the mortality rate caused by IAV infection. Silibinin has strong immunomodulatory properties, can inhibit IAV infection, and reduces lung tissue damage in a dose-dependent manner.