Delphinidin protects β2m-/Thy1+ bone marrow-derived hepatocyte stem cells against TGF-β1-induced oxidative stress and apoptosis through the PI3K/Akt pathway in vitro.

β2m-/Thy1+ bone marrow-derived hepatocyte stem cells (BDHSCs) have a potential to be applied for cellular treatment in liver cirrhosis. However, the resultant tissue regeneration is restricted by transplanted cells' death. The accumulation of transforming growth factor beta 1 (TGF-β1) in liver fibrosis local microenvironment may play an essential role in the rapid cell death of implanted β2m-/Thy1+ BDHSCs. The main mechanism of poor survival of the target stem cells is still unknown. Delphinidin, an anthocyanidin, has potent antioxidant and anti-inflammatory activities. However, whether this bio-active ingredient can substantially contribute to β2m-/Thy1+ BDHSCs' protection from TGF-β1 induced apoptosis in vitro remains to be elucidated. In the present research, we determined whether delphinidin pretreatment can improve the survival of β2m-/Thy1+ BDHSCs during exposure to TGF-β1 and elucidated its underlying mechanisms. By using TGF-β1, we induced the apoptosis of β2m-/Thy1+ BDHSCs and assessed the apoptotic rates up to 24 h by flow cytometry. β2m-/Thy1+ BDHSC proliferation was gauged using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl- 2H-tetrazolium bromide (MTT) assay. The expression grades of Bcl-2, Akt, caspase-3, and Bax were observed through Western blot analysis. We found that delphinidin can significantly impede TGF-β1-induced apoptosis dose-dependently, scavenge reactive oxygen species (ROS), and inhibit the discharge of caspase-3 in β2m-/Thy1+ BDHSCs. We also demonstrated that delphinidin can activate the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The suppression of ROS and succeeding apoptosis was achieved by pretreatment with LY294002, a PI3K/Akt pathway inhibitor. In summary, our findings revealed that delphinidin can protect β2m-/Thy1+ BDHSCs from apoptosis and ROS-dependent oxidative stress induced by the TGF-β1 via PI3K/Akt signaling pathway. On the basis of these data, delphinidin can be regarded as a promising anti-apoptotic agent for enhancing β2m-/Thy1+ BDHSC survival during cell transplantation in liver cirrhosis patients.

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