Antioxidant effects of Cirsium setidens extract on oxidative stress in human mesenchymal stem cells.
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.
Department of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, South Gyeongsang 50612, Republic of Korea.
Jun Hee
JH
Lee
Department of Herb Research, Jeollanamdo Development Institute of Traditional Korean Medicine, Jangheung, South Jeolla 59338, Republic of Korea.
Ho Kyung
HK
Jung
Department of Biochemistry, Medical Science Research Institute, Soonchunhyang University College of Medicine, Cheonan, South Chungcheong 31151, Republic of Korea.
Yong-Seok
YS
Han
Department of Biochemistry, Medical Science Research Institute, Soonchunhyang University College of Medicine, Cheonan, South Chungcheong 31151, Republic of Korea.
Yeo Min
YM
Yoon
Department of Biochemistry, Medical Science Research Institute, Soonchunhyang University College of Medicine, Cheonan, South Chungcheong 31151, Republic of Korea.
Chul Won
CW
Yun
Department of Urology, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea.
Hwa Yeon
HY
Sun
Department of Neurology, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Hyun Woo
HW
Cho
Department of Biochemistry, Medical Science Research Institute, Soonchunhyang University College of Medicine, Cheonan, South Chungcheong 31151, Republic of Korea.
Sang Hun
SH
Lee
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002460:Cell Line; D031180:Cirsium / Q000737:chemistry*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide