Antioxidant effects of Cirsium setidens extract on oxidative stress in human mesenchymal stem cells

Abstract

Human mesenchymal stem cells (MSCs) may be used in cell-based therapy to promote neovascularization for the treatment of ischemic diseases. However, high levels of reactive oxygen species (ROS) derived from the pathophysiological ischemic environment induce senescence and apoptosis of MSCs, resulting in reduced functionality and defective neovascularization. Therefore, the present study aimed to determine the protective effects of Cirsium setidens, a natural product, on oxidative stress-induced apoptosis in MSCs. The present study investigated for the change of ROS levels in MSCs using ROS assays. In addition, cell viability determined by MTT and TUNEL assays. Western blot analysis was performed to investigate the change of apoptosis-associated proteins in MSCs. Treatment of MSCs with hydrogen peroxide (H2O2; 200 µM) significantly increased intracellular ROS levels and cell death; however, pretreatment with C. setidens (100 µg/ml) suppressed H2O2-induced ROS generation and increased the survival of MSCs. H2O2-induced ROS production increased the levels of phosphorylated-p38 mitogen activated protein kinase, c-Jun N-terminal kinase, ataxia telangiectasia mutated and p53; these increases were inhibited by pretreatment with C. setidens. In addition, C. setidens inhibited ROS-induced apoptosis of MSCs by increasing the expression levels of the anti-apoptotic protein B-cell lymphoma 2 (BCL-2), and decreasing the expression levels of the proapoptotic protein BCL-2-associated X protein. These findings indicated that pretreatment of MSCs with C. setidens may prevent ROS-induced oxidative injury by regulating the oxidative stress-associated signaling pathway, and suppressing the apoptosis-associated signal pathway. Therefore, C. setidens may be developed as a beneficial broad-spectrum agent for enhancing the effectiveness of MSC transplantation in the treatment of ischemic diseases.

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

“…Recently, a number of studies have been reported that aimed to improve the survival rate of MSCs thereby overcoming the limitations of stem cells as cell‐based therapeutic agents. 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 .…”

“…Treatment with Cirsium setidens extract suppressed H 2 O 2 -induced ROS generation in MSCs and increased their survival rate. 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.…”

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

“…Apocynin, a phenolic compound, partially reverses the ageing process and enhances the potential for osteogenesis in ageing MSCs by suppressing NOX . 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 .…”

Protective effect of gigantol against hydrogen peroxide‑induced apoptosis in rat bone marrow mesenchymal stem cells through the PI3K/Akt pathway

“…MSC therapy is considered a novel and promising strategy for the treatment of ischemic stroke, and may exert neuroprotective effects and promote the repair of neurons by secreting various neural trophic factors and replacing damaged neurons (4). However, the ischemic microenvironment negatively influences the survival rate of transplanted MSCs in injured CNS conditions due to oxidative stress (5,6). Thus, improving the survival of MSCs during oxidative stress may improve the efficacy of MSC-based therapies.…”