Mesenchymal stem cells (MSCs) from bone marrow have become therapeutically important agents because of their ability to localize specifically to injury sites and to differentiate into various cell types.However,the poor survival of the implanted cells hampered progress in stem cell therapy.One reason is that transplanted cells exposed to a hypoxic,nutrient-poor environment that are often bombarded by reactive oxygen species.Chlorogenic acid as an antioxidant exists widely in edible and medicinal plants,and can protect cell against apoptosis induced by oxidative stress.In this research,MSCs preincubated with or without Chlorogenic acid were exposed to H2O2 for different time,FOXO1,FOXO3,FOXO4 mRNA expression.reactive oxygen species,Akt phosphorylation and Bcl-2 level were measured.We found that the underlying mechanisms of Chlorogenic acid in protecting MSCs from H2O2-induced apoptosis were related to FOXO1,FOXO3,FOXO4 mRNA expression,reactive oxygen species Akt phosphorylation and Bcl-2.we found that Chlorogenic acid increased:(1) mitochondrial membrane potential,(2) the experssion of FOXOs genes,(3) antiapoptotic protein Bcl-2,and attenuated H202-induced reactive oxygen species generation.Our data demonstrated that Chlorogenic acid played important roles in protecting MSCs against apoptosis under oxidative stress in vitro.In summary,the present investigation indicates that Chlorogenic acid appears to confer its beneficial effects via activating PI3K/Akt and upregulator of FOXO1,FOXO3,FOXO4 genes expression,via inhibiting reactive oxygen species activation and increasing Bcl-2 protein expression.These findings indicate that Chlorogenic acid is a promising antiapoptotic agent for improving MSCs survival in cell transplantation.