Protective Effect of Ginsenoside Rg1 on Hematopoietic Stem/Progenitor Cells through Attenuating Oxidative Stress and the Wnt/β-Catenin Signaling Pathway in a Mouse Model of d-Galactose-induced Aging.
Stem cell senescence is an important and current hypothesis accounting for organismal aging, especially the hematopoietic stem cell (HSC). Ginsenoside Rg1 is the main active pharmaceutical ingredient of ginseng, which is a traditional Chinese medicine. This study explored the protective effect of ginsenoside Rg1 on Sca-1⁺ hematopoietic stem/progenitor cells (HSC/HPCs) in a mouse model of d-galactose-induced aging. The mimetic aging mouse model was induced by continuous injection of d-gal for 42 days, and the C57BL/6 mice were respectively treated with ginsenoside Rg1, Vitamin E or normal saline after 7 days of d-gal injection. Compared with those in the d-gal administration alone group, ginsenoside Rg1 protected Sca-1⁺ HSC/HPCs by decreasing SA-β-Gal and enhancing the colony forming unit-mixture (CFU-Mix), and adjusting oxidative stress indices like reactive oxygen species (ROS), total anti-oxidant (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and malondialdehyde (MDA). In addition, ginsenoside Rg1 decreased β-catenin and c-Myc mRNA expression and enhanced the phosphorylation of GSK-3β. Moreover, ginsenoside Rg1 down-regulated advanced glycation end products (AGEs), 4-hydroxynonenal (4-HNE), phospho-histone H2A.X (r-H2A.X), 8-OHdG, p16(Ink4a), Rb, p21(Cip1/Waf1) and p53 in senescent Sca-1⁺ HSC/HPCs. Our findings indicated that ginsenoside Rg1 can improve the resistance of Sca-1⁺ HSC/HPCs in a mouse model of d-galactose-induced aging through the suppression of oxidative stress and excessive activation of the Wnt/β-catenin signaling pathway, and reduction of DNA damage response, p16(Ink4a)-Rb and p53-p21(Cip1/Waf1) signaling.
Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. jingli2523@gmail.com.|Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China. jingli2523@gmail.com.
Jing
J
Li
Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. cqmucdc@sohu.com.
Dachuan
D
Cai
Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China. moliliuxiang@aliyun.com.
Xin
X
Yao
Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. cqzyi531@gmail.com.
Yanyan
Y
Zhang
Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. cqcb9866@outlook.com.
Linbo
L
Chen
Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. xhjke0316@gmail.com.
Pengwei
P
Jing
Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. wanglu99@sina.com.|Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. wanglu99@sina.com.
Lu
L
Wang
Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. ypwangcq@aliyun.com.|Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. ypwangcq@aliyun.com.
Yaping
Y
Wang
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005690:Galactose / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
D000975:Antioxidants; D036145:Ginsenosides; D006657:Histones; D017382:Reactive Oxygen Species; D014815:Vitamins; D051176:beta Catenin; D014810:Vitamin E; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000071679:Glycogen Synthase Kinase 3 beta; C035054:ginsenoside Rg1; D005690:Galactose
">d-galactose; Wnt/β-catenin; cellular senescence; ginsenoside Rg1; hematopoietic stem/progenitor cell (HSC/HPC); oxidative stress