This study aims to investigate the effects of saikosaponin D (SD) on the apoptosis of diffuse large B-cell lymphoma (DLBCL) through the inorganic pyrophosphatase 1 (PPA1).This study utilized high PPA1-expressing cell lines,HBL-1 and U2932,treated with varying concentrations of SD.The proliferation and apoptosis of the cells were assessed using the MTT and TUNEL assay,while ELISA and WB were employed to analyze PPA1 activity and the expression of relevant proteins.Additionally,this study established a cell transplantation tumor model for in vivo validation.The results demonstrated that SD significantly inhibited cell proliferation and induced apoptosis by reducing activity and expression of PPA1,increasing levels of cleaved cysteine-aspartic protease 3 (cleaved Caspase-3) and Bcl-2-associated X protein (Bax),and decreasing B-cell lymphoma 2 (Bcl-2) expression.In the cell transplantation tumor model,the tumor volume in the PPA1 down-regulated group was significantly lower than that in the PPA1 down-regulated control group,and the tumor volume in the SD treatment group was also significantly reduced in comparison with DMSO control group.In summary,SD promotes apoptosis in DLBCL cells by inhibiting PPA1,highlighting its potential as an anti-DLBCL drug.