PMID- 27294914 OWN - NLM STAT- MEDLINE DCOM- 20170315 LR - 20220330 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 17 IP - 6 DP - 2016 Jun 9 TI - Protective Effect of Ginsenoside Rg1 on Hematopoietic Stem/Progenitor Cells through Attenuating Oxidative Stress and the Wnt/beta-Catenin Signaling Pathway in a Mouse Model of d-Galactose-induced Aging. LID - 10.3390/ijms17060849 [doi] LID - 849 AB - 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-beta-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 beta-catenin and c-Myc mRNA expression and enhanced the phosphorylation of GSK-3beta. 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/beta-catenin signaling pathway, and reduction of DNA damage response, p16(Ink4a)-Rb and p53-p21(Cip1/Waf1) signaling. FAU - Li, Jing AU - Li J AD - Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. jingli2523@gmail.com. AD - Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China. jingli2523@gmail.com. FAU - Cai, Dachuan AU - Cai D AD - Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. cqmucdc@sohu.com. FAU - Yao, Xin AU - Yao X AD - Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China. moliliuxiang@aliyun.com. FAU - Zhang, Yanyan AU - Zhang Y AD - Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. cqzyi531@gmail.com. FAU - Chen, Linbo AU - Chen L AD - Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. cqcb9866@outlook.com. FAU - Jing, Pengwei AU - Jing P AD - Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. xhjke0316@gmail.com. FAU - Wang, Lu AU - Wang L AD - Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. wanglu99@sina.com. AD - Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. wanglu99@sina.com. FAU - Wang, Yaping AU - Wang Y AD - Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China. ypwangcq@aliyun.com. AD - Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. ypwangcq@aliyun.com. LA - eng PT - Journal Article DEP - 20160609 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antioxidants) RN - 0 (Ginsenosides) RN - 0 (Histones) RN - 0 (Reactive Oxygen Species) RN - 0 (Vitamins) RN - 0 (beta Catenin) RN - 1406-18-4 (Vitamin E) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - PJ788634QY (ginsenoside Rg1) RN - X2RN3Q8DNE (Galactose) SB - IM MH - Aging/drug effects/*metabolism MH - Animals MH - Antioxidants/*pharmacology MH - Galactose/pharmacology MH - Ginsenosides/*pharmacology MH - Glutathione Peroxidase/metabolism MH - Glycogen Synthase Kinase 3 beta/metabolism MH - Hematopoietic Stem Cells/cytology/drug effects/*metabolism MH - Histones/metabolism MH - Male MH - Malondialdehyde/metabolism MH - Mice MH - Mice, Inbred C57BL MH - *Oxidative Stress MH - Reactive Oxygen Species/metabolism MH - Superoxide Dismutase/metabolism MH - Vitamin E/pharmacology MH - Vitamins/pharmacology MH - *Wnt Signaling Pathway MH - beta Catenin/metabolism PMC - PMC4926383 OTO - NOTNLM OT - ">d-galactose OT - Wnt/beta-catenin OT - cellular senescence OT - ginsenoside Rg1 OT - hematopoietic stem/progenitor cell (HSC/HPC) OT - oxidative stress EDAT- 2016/06/15 06:00 MHDA- 2017/03/16 06:00 PMCR- 2016/06/01 CRDT- 2016/06/14 06:00 PHST- 2016/04/18 00:00 [received] PHST- 2016/05/19 00:00 [revised] PHST- 2016/05/25 00:00 [accepted] PHST- 2016/06/14 06:00 [entrez] PHST- 2016/06/15 06:00 [pubmed] PHST- 2017/03/16 06:00 [medline] PHST- 2016/06/01 00:00 [pmc-release] AID - ijms17060849 [pii] AID - ijms-17-00849 [pii] AID - 10.3390/ijms17060849 [doi] PST - epublish SO - Int J Mol Sci. 2016 Jun 9;17(6):849. doi: 10.3390/ijms17060849.