Objective · To investigate the effect of anemarrhena saponin (ZMS) on mRNA level of brain-derived neurotrophic factor (BDNF) and relevant mechanism in oxidative stress damage of SH-SY5Y cells. Methods · SH-SY5Y cells treated with H2O2 were chosen as cell models of oxidative stress. Cell viability was determined using cell counting kit-8 (CCK-8). The mRNA levels of BDNF and its important transcripts were detectedquantitative real-time PCR (qPCR). The histone deacetylases (HDACs) activity fluorescence quantification assay kit was used to measure the effect of ZMS on HDACs activity. Western blotting was used to detect the protein levels of acetylated histone H3, acetylated histone H4, specific acetylation site-related proteins, and HDAC1/2/3. Results · qPCR showed that ZMS could increase the mRNA levels of BDNF and its transcript Ⅳ in the cell models. Western blotting showed that ZMS pretreatment could increase the protein levels of acetylated histone H3, acetylated histone H4 and acetylated histone H3K14, and there was no significant effect on protein levels of HDAC1/2/3. In addition, HDACs activity fluorescence quantification assay kit showed that ZMS could inhibit HDACs activity significantly. Conclusion · ZMS can increase the mRNA levels of BDNF and its transcript Ⅳ in oxidative stress damage cell models, which may be related to the regulation of histone acetylation level.