Angelica sinensis polysaccharides alleviate the oxidative burden on hematopoietic cells by restoring 5-fluorouracil-induced oxidative damage in perivascular mesenchymal progenitor cells

Context 5-Fluorouracil (5-FU)-injured stromal cells may cause chronic bone marrow suppression; however, the underlying mechanism remains unclear. Angelica sinensis polysaccharide (ASP), the main biologically active ingredient of the Chinese herb, Angelica sinensis (Oliv.) Diels (Apiaceae), may enrich the blood and promote antioxidation. Objective This study investigated the protective antioxidative effects of ASP on perivascular mesenchymal progenitors (PMPs) and their interactions with hematopoietic cells. Materials and methods PMPs were dissociated from C57BL/6 mouse femur and tibia and were subsequently divided into the control, ASP (0.1 g/L), 5-FU (0.025 g/L), and 5-FU + ASP (pre-treatment with 0.1 g/L ASP for 6 h, together with 0.025 g/L 5-FU) then cultured for 48 h. Hematopoietic cells were co-cultured on these feeder layers for 24 h. Cell proliferation, senescence, apoptosis, and oxidative indices were detected, along with stromal osteogenic and adipogenic differentiation potentials. Intercellular and intracellular signaling was analyzed by real-time quantitative reverse transcription polymerase chain reaction and Western blotting. Results ASP ameliorated the reactive oxygen species production/scavenge balance in PMPs; improved osteogenic differentiation; increased SCF, CXCL12, VLA-4/VCAM-1, ICAM-1/LFA1, and TPO/MPL, Ang-1/Tie-2 gene expression. Further, the ASP-treated feeder layer alleviated hematopoietic cells senescence (from 21.9 +/- 1.47 to 12.1 +/- 1.13); decreased P53, P21, p-GSK-3 beta, beta-catenin and cyclin-D1 protein expression, and increased glycogen synthase kinase (GSK)-3 beta protein expression in co-cultured hematopoietic cells. Discussion and conclusions ASP delayed oxidative stress-induced premature senescence of 5-FU-treated feeder co-cultured hematopoietic cells via down-regulation of overactivated Wnt/beta-catenin signaling. These findings provide a new strategy for alleviating myelosuppressive stress.

Automated summary

This study investigated the protective antioxidative effects of Angelica sinensis polysaccharide (ASP) on perivascular mesenchymal progenitors (PMPs) and their interactions with hematopoietic cells. The results showed that ASP improved the oxidative balance in PMPs, promoted osteogenic differentiation, and increased the expression of key genes. Additionally, the ASP-treated feeder layer alleviated senescence of hematopoietic cells and delayed premature senescence of 5-FU-treated cells by down-regulating Wnt/beta-catenin signaling. These findings provide a new strategy for alleviating myelosuppressive stress.