Abstract: Objective To investigate the therapeutic effects of saikosaponin D (SSD) on idiopathic pulmonary fibrosis(IPF). Methods Human fetal lung fibroblasts HFL1 cells were divided into control, model (TGF-β1, 5 ng/mL), SSD intervention (2.5/5/10 μmol/L), and positive control (rapamycin, 20 nmol/L) groups. Cell proliferation was assessed by CCK-8 assay; the expression of fibrosis- and pyroptosis-related protein were determined by Western blot; the expression of fibrosis-related genes was measured by RT-qPCR; cell damage was evaluated by LDH release assay; apoptosis was examined by flow cytometry; pyroptosis-related protein level was detected by immunofluorescence method and pyroptosis was observed by microscopy. Results Compared with the control group, TGF-β1 significantly promoted HFL1 cell proliferation (P＜0.05); compared with the model group, SSD inhibited cell proliferation in a concentration-dependent manner (P＜0.05). Compared with the control group, the expression of key proteins in the mTORC1/4E-BP1 pathway and pyroptosis-related proteins was significantly increased in the model group (P＜0.05); compared with the model group, their expression was significantly decreased in the SSD-treated groups (P＜0.05). Compared with the control group, the mRNA expression of fibronectin, collagen I, IL-1β, and IL-18 was significantly increased in the model group (P＜0.05); compared with the model group, their expression was significantly decreased after SSD treatment (P＜0.05). Compared with the control group, LDH release was significantly increased in the model group (P＜0.05); compared with the model group, it was significantly decreased in the SSD-treated groups (P＜0.05). Immunofluorescence showed that the expression of Ki67 and vimentin was significantly increased in the model group compared with the control group (P＜0.05), and was significantly decreased after SSD treatment compared with the model group (P＜0.05). Conclusions SSD alleviates TGF-β1-induced pulmonary fibrosis by inhibiting pyroptosis, reducing fibrotic protein expression and suppressing inflammatory cytokine release.

Key words: saikosaponin D, pyroptosis, pulmonary fibrosis