Inhibitory Effect And Mechanism Study Of Compound Traditional Chinese Medicine Against Influenza A Virus

Influenza A virus is a virus that causes acute respiratory infection in human and animals.The traditional herb medicine possess comprehensive effects on viral replication inhibition,cytopathy prevention,immune function adjustment,pulmonary circulation improvement,pain or inflation remission,and it’s impossible to get drug resistance.Selection for safe and effective traditional Chinese medicine has been a hot spot in prevention and treatment of influenza A viral infection.In this study,the inhibitory effect of Compound traditional Chinese medicine on influenza A virus was determined by in vitro and in vivo experiments.Furthermore,mechanism study of Compound traditional Chinese medicine against influenza A virus was discussed.The study provides the experimental basis for clinical application of Compound traditional Chinese medicine,and is of great significance for the prevention and treatment of influenza virus.In vitro experimental results showed that the median toxic concentrations(TC50)of Compound traditional Chinese medicine on MDCK cells was 1596μg/mL.Experiment of effect of Compound traditional Chinese medicine against influenza virus H1N1 showed that average EC50(Half effective concentration)of Compound traditional Chinese medicine was 208.9,207.4 and 237.1μg/mL respectively;TI(Treatment index)was 7.6,7.7 and 6.7 respectively for 3 different effectiveness evaluations,i.e.inhibition on virus proliferation after adsorption,prevention effect on virus adsorption,direct killing the virus effect,Experiment of effect of Compound traditional Chinese medicine against H7N7 showed that under the same 3 drug effectiveness evaluations,average EC50 of Compound traditional Chinese medicine was 212.4,338.7 and 360.9μg/mL respectively;TI was 7.5,4.7and 4.4 respectively.In vivo experimental results showed that protection of Compound traditional Chinese medicine on infected mice was as following:The average mice survival dates was 8.7d in virus control group,11.7d in medium dose Compound traditional Chinese medicine group,indicating significant difference between the two groups(P<0.01).The mice mortality rate was 80%in virus control group,33.3%in medium dose group,showing significant difference between the two groups(P<0.01).Pulmonary inflammation inhibition effect of Compound traditional Chinese medicine on infected micewas as following:Lung index in medium dose of Compound traditional Chinese medicine group was significantly decreased than the virus control group(P<0.01).Lung index in high and low dose of Compound traditional Chinese medicine groups were lowered than virus control group(P<0.05).The virus HA titers in treatment groups decreased and significantly different from the virus control group(P<0.01).Mice in virus control group showed heavy lesions,such as capillary blood vessels were congested,majority of pulmonary alveolar structures were destructed,part of lung tissue was consolidated and fused,alveolar septum was thickened,alveolar cavity and interstitial inflammatory cell infiltration were observed.After Compound traditional Chinese medicine treatment,animals showed apparent health improvement.Results of the preliminary mechanism study on of the drug showed that(1)The effect of Compound traditional Chinese medicine on immunity and immunologic function of infected mice:Compared with virus control group,spleen index and thymus index were significantly increased(p<0.05)in medium dose treatment group.Compared with virus control group,T and B lymphocyte A values were significantly increased(p<0.05)in medium dose treatment group.(2)The impact of Compound traditional Chinese medicine on cytokine expression in infected mice:Compared with virus control group,IL-6 was significantly decreased(p<0.05)and IL-10 was significantly increased(p<0.05)in medium dose treatment group;TNF-α level was significantly decreased(p<0.01)and IFN-γ was significantly increased(p<0.01)in medium and low dose groups;IFN-y level in high dose groups was significantly increased(p<0.05).(3)The impact of Compound traditional Chinese medicine on anti-oxidation ability in infected mice:compared with virus control group,SOD value was g significantly increased(p<0.01)in medium and low dose treatment group,SOD value was significantly increased(p<0.05)in high dose treatment groups,MDA value was significantly increased(p<0.01)in high,medium and low dose groups.To sum up,Compound traditional Chinese medicine has a significant inhibition effect against influenza A virus infection in vivo and in vitro.In addition,Compound traditional Chinese medicine has indirect antiviral effects by regulating immune function and cytokine secretion,and reducing the oxidative stress caused by influenza Avirus.