Protective effect of berberine against oxidative stress-induced apoptosis in rat bone marrow-derived mesenchymal stem cells

Abstract

Abstract. Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to be used for the treatment of delayed union, nonunion or persistent bone defects in MSC-based cell therapy. However, implantation of BMSCs into the fracture site is confronted with apoptosis on account of harsh conditions and oxidative stress. In the present study, the anti-apoptotic effects of berberine (BBR) on BMSCs subjected to hydrogen peroxide (H 2 O 2 ) are investigated, and the potential underlying mechanisms are explored. Oxidative injury was induced by exposure to H 2 O 2 , and cell viability was assessed using a cell counting kit-8 assay. The apoptosis of BMSCs was measured by Hoechst 33258 and Annexin V-fluorescein isothiocyanate/propidium iodide assay. Reactive oxygen species staining and superoxide dismutase (SOD) assay were applied to assess the anti-oxidative effect of BBR. Finally, western blot was performed to measure the expression levels of phosphorylated (p)-Akt, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cleaved caspase-3. In the present study, it was identified that BBR remarkably attenuated H 2 O 2 -induced apoptotic cell death via quenching ROS production and increasing SOD activity. Further studies indicated that BBR can reduce apoptosis by upregulating the expression level of p-Akt and Bcl-2, and downregulating the expression levels of Bax and cleaved caspase-3. Taken together, the results of the present study demonstrate that pretreatment with BBR could alleviate H 2 O 2 -induced apoptosis in rat BMSCs in vitro.

Protective effects of hepatocyte growth factor gene overexpression against hydrogen peroxide‐induced apoptosis in mesenchymal stem cells

“…23 Berberine also exhibited protective effect against oxidative stress-induced apoptosis in MSCs. 24 Our results also revealed that NAC, a known antioxidant, exerted protective effect against H 2 O 2 -induced apoptosis in MSCs. H 2 O 2 is known to induce apoptosis by inducing inflammation and oxidative stress in cells.…”

“…Treatment with Cirsium setidens extract suppressed H 2 O 2 ‐induced ROS generation in MSCs and increased their survival rate . Berberine also exhibited protective effect against oxidative stress‐induced apoptosis in MSCs . Our results also revealed that NAC, a known antioxidant, exerted protective effect against H 2 O 2 ‐induced apoptosis in MSCs.…”

Berberine impairs embryonic development in vitro and in vivo through oxidative stress‐mediated apoptotic processes

“…However, previous studies have also reported that berberine attenuates H 2 O 2 -induced oxidative injury or apoptosis in motor neuron-like cells, 19 smooth muscle cells, 20 and endothelial and mesangial cells 21 and rBMSCs. 22 The ambiguous roles of berberine in inducing or preventing intracellular ROS production and the corresponding regulatory mechanisms are unclear and will require further investigation.…”

“…Interestingly, previous studies have found that berberine also has the ability to attenuate H 2 O 2 ‐induced oxidative injury and apoptosis in motor neuron‐like cells, smooth muscle cells, and endothelial and mesangial cells . A recent study further demonstrated that berberine protects primary cultured rat bone marrow‐derived stem cells (rBMSCs) against H 2 O 2 ‐induced apoptosis in vitro by enhancing resistance to oxidative stress . These ambiguous effects of berberine—inducing or preventing apoptosis—and the regulatory mechanisms that underlie them are unclear and need further investigation.…”

Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

“…Both lycopene and Cirsium setidens pretreatments suppressed H 2 O 2 ‐induced ROS generation and increased survival of MSCs by attenuating the phosphorylated p38‐MAPK, JNK, ATM and p53 signalling pathways . Berberine, a natural isoquinoline quaternary alkaloid extracted from the Chinese herb Huanglian, significantly prevents H 2 O 2 ‐induced apoptotic progression by reducing ROS production and levels of apoptosis‐related proteins, while increasing SOD activity and p‐AKT and Bcl‐2 levels . Astragalus polysaccharide, which is isolated from Astragalus membranaceus, is able to counter the reductions in proliferation and pluripotency and to prevent the increased apoptosis and senescence in MSCs induced by ferric ammonium citrate (FAC) …”