Synergistic activity of baicalein with ribavirin against influenza A (H1N1) virus infections in cell culture and in mice

► We investigated the synergistic activity of baicalein with ribavirin against influenza virus in cell culture and in mice. ► Study demonstrated that the compound inhibited the synthesis of viral matrix protein gene greater than ribavirin alone. ► Higher survival rate, lower body weight loss, fewer inflammatory responses in the lungs of infected were observed. Baicalein is a flavonoid derived from the root of Scutellaria baicalensis, a traditional Chinese medicine that has been used for hundreds of years; baicalein has also been demonstrated to have antiviral activity with low toxicity. The synergistic activity of baicalein with ribavirin against influenza virus infections in cell culture and in mice was investigated for the first time in our research. In vitro, maximal synergy at lower concentrations of baicalein (0.125 μg/ml) and ribavirin (12.5 μg/ml) was observed, and the reduced expression of the viral matrix protein (M) gene suggested that drug combinations caused greater inhibition than ribavirin alone, especially the combination of 0.5 μg/ml baicalein and 5 μg/ml ribavirin. In vivo, combinations of baicalein and ribavirin provided a higher survival rate and lower body weight loss. Moreover, fewer inflammatory responses in the lungs of mice infected with virus and treated with baicalein and ribavirin were observed; the mean scores were 1.0, 0.8, and 1.2 with the doses of ribavirin at 50 mg/kg/d combined with baicalein at 100 mg/kg/d, 200 mg/kg/d, and 400 mg/kg/d respectively, while the placebo group had a mean pathology score of 3.2. Thus, the data demonstrates that combinations of baicalein and ribavirin provide better protection against influenza infection than each compound used alone and could potentially be clinically useful.