Effect of the Internal Septum Extract of the Walnut Kernel on the Mesenchymal Stem Cells Cycle and MSCs-derived Insulin-Producing Β-cells Differentiation and Glucose Uptake

Abstract

Background: For years, scientists have been striving to identify compounds to improve the characteristics and functions of cells for therapeutic applications. Objectives: This study aimed to evaluate the effect of the aqueous decoction of the internal septum of the walnut kernel (DISWK) on the survival, total antioxidant capacity (TAC), and cell cycle of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs). We also evaluated the expression of genes involved in pancreatic insulin-producing β-cell (IPCs) commitment and glucose uptake in MSCs-derived IPCs. Methods: The rBM-MSCs were isolated, and then the cytotoxic and antioxidant effects of DISWK on the cells were examined by the MTT and TAC assays, respectively. Moreover, the influence of DISWK on the rBM-MSCs cell cycle was evaluated by PI-staining and flow-cytometry analysis. Next, the rBM-MSCs were transdifferentiated into IPCs treated with DISWK. Finally, Ins1/2, Insr, Glut1, Glut4, and Pdx1 genes expression was investigated in the DISWK-treated IPCs by qRT-PCR. Results: The results indicated that DISWK significantly reduced the viability of rBM-MSCs in a dose- and time-dependent manner and decreased their TAC in long-term cultures. Moreover, it suppressed the rBM-MSCs cell cycle at S and G2 phases. The gene expression analysis showed that DISWK significantly upregulated Ins1/2, Insr, and Glut1 genes and downregulated Pdx1 gene in the rBM-MSCs-derived IPCs. Conclusions: Decoction of the internal septum of walnut kernel suppresses the MSCs cell cycle and may prevent IPCs development via inhibiting Pdx1. It may also help glucose uptake by upregulating Ins1/2, Insr, and Glut1 genes expression in MSCs-derived IPCs.