Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

Abstract

Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica Sinensis), on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We further found that multiple mechanisms were involved: (1) ASP treatment prevented oxidative damage as total antioxidant capacity was increased and levels of reactive oxygen species (ROS), 8-OHdG, and 4-HNE were declined, (2) ASP reduced the expression of γ-H2A.X which is a DNA double strand breaks (DSBs) marker and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and p19Arf-p21Cip1/Waf senescent pathways, and (3) ASP inhibited the excessive activation of Wnt/β-catenin signaling in aged HSC/HPCs, as the expressions of β-catenin, phospho-GSK-3β, and TCF-4 were decreased, and the cyto-nuclear translocation of β-catenin was inhibited. Moreover, compared with the positive control of Vitamin E, ASP exhibited a better antiaging effect and a weaker antioxidation ability, suggesting a novel protective role of ASP in the hematopoietic system.

Angelica sinensis Polysaccharides Ameliorate Stress-Induced Premature Senescence of Hematopoietic Cell via Protecting Bone Marrow Stromal Cells from Oxidative Injuries Caused by 5-Fluorouracil

“…Both cell death and cellular senescence are important responses to stress-associated stimuli. It was demonstrated that 5-FU exerts anticancer effects mainly by inhibiting tumor cell proliferation, activating Bax and P53, and/or caspase-dependent mechanism [ 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. Annexin V/Propidium iodide (PI) staining assay is commonly applied to discern necrotic cells and apoptotic cells, further to quantify apoptosis.…”

“…ASP are major effective ingredients in Chinese Angelica with significant bioactivities including antioxidant, antitumor, hematopoietic regulatory, immunomodulatory, and radiation protective effects [ 68 , 69 , 70 , 71 , 72 , 73 ]. Our recent studies indicated extraordinary anti-aging roles of ASP which protected HSPCs against radiation-induced or d -Galactose-induced aging [ 74 ]. On this basis, our data clarified for the first time the protective effect of ASP on BMSCs from 5-FU injury, especially the protective effect on hematopoietic cells against SIPS via alleviating oxidative stress, preventing oxidative DNA damage, enhancing intercellular communication, and promoting hematopoietic stimulating factors originated from 5-FU injured BMSCs.…”

Anti-Aging Effect of Chitosan Oligosaccharide on d-Galactose-Induced Subacute Aging in Mice

“…d -gal is a normal nutrient that naturally exists in the body [ 21 ]. As a certain dose of d -gal is injected into the mice within a period of time, the concentration of it in cells will be too high to be catalyzed by galactose oxidase to aldose and hydrogen peroxide, finally generating superoxide anions [ 22 ]. The oxidation in the body produces a large number of free radicals, which are beyond the body’s scavenging capacity and lead to lipid peroxidation; meanwhile, the final decomposition products (such as MDA) can directly or indirectly combine with proteins, nucleic acids, phospholipids, and other substances, not only destroying the chemical structure of intracellular life substances and disrupting cell function, but also damaging normal tissue cells, as well as affecting the normal osmotic pressure, which further lead to metabolic disorders of vital organs and eventually organism aging [ 23 , 24 ].…”

New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach

“…Cheng et al [196] showed that ASP restored cognitive impairment caused by D-gal administration, promoted neural 9 Oxidative Medicine and Cellular Longevity stem cell (NSC) proliferation, attenuated D-gal-induced NSC senescence, decreased the level of oxidative stress by enhancing antioxidative capacity, and decreased the levels of inflammatory cytokines of NSCs. These events slowed the aging speed by enhancing the antioxidant and antiinflammatory capacity and downregulating the p53/p21 signaling pathway [197,198].…”