Dl-3-n-Butylphthalide enhances the survival of rat bone marrow stem cells via a reactive oxygen species mediated Erk1/2 signaling pathway.

Abstract

Survival of bone marrow stem cells (BMSCs) is crucial for successful bone marrow transplantation. However, the underlying molecular mechanisms remain inadequately understood. Our previous research has demonstrated that dl-3-n-butylphthalide (NBP) can protect rat BMSCs from cell death via its antioxidative properties and by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. The findings suggest that the PI3K/Akt pathway may be one of the primary targets through which NBP exert its protective effects. In this study, we explored an additional signaling pathway to further elucidate the molecular mechanisms involved in NBP-mediated protection against oxidative stress injury in rat BMSCs (rBMSCs). Oxidative stress was induced in rBMSCs using hydrogen peroxide (H₂O₂), imitating the cerebral ischemia microenvironment surrounding transplanted cells in vitro. The protective effects of NBP on rBMSCs against apoptosis were observed, achieving by decreasing the level of reduce reactive oxygen species (ROS) and malondialdehyde (MDA) while simultaneously increasing the concentration of superoxide dismutase (SOD). Notably, these protective effects were partially inhibited by U0126, an extracellular signal-regulated kinase1/2 (Erk1/2) inhibitor, which enhanced the suppression of NBP's antiapoptotic effects. Our results indicated that NBP could protect rBMSCs from apoptosis through modulation of ROS/Erk pathways. Further investigations are warranted to clarify the unknown mechanisms.