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The first two authors contributed equally to this study To date there has been no valid treatment for herpes simplex encephalitis (HSV). This study explores the protective activity of ethanol extract of Cynanchum paniculatum (bunge) kitagawa for treatment of HSV. Cell models and animal models were established and divided into 4 groups: normal group, virus group, cynanchum paniculatum group and Dexamethasone group. Flow cytometry was employed to detect apoptosis of cell model and TUNEL assay was chosen to detect apoptosis of animal tissues. The survival time of the animal models was observed. ELISA was used to measure TNF-a expression and the Greiss method to measure Nitric Oxide (NO) expression in the mouse brain. As a result, it was found that extract of Cynanchum paniculatum can improve the survival rate of HSV-infected mice. The extract could prevent apoptosis in the neuron cell model and reduce apoptosis rate in brain tissue after HSV infection. With the extract intervention, TNF-a and NO levels in brain tissue were significantly decreased in the animal model. In conclusion, the extract of Cynanchum paniculatum can prevent HSVinducing impairment in the cell and animal model of HSE.Herpes simplex encephalitis (HSE) is a kind of viral encephalitis that attacks neonates as well as older children and adults (l) and is a significant cause of morbidity and mortality (2). Nowadays, the