Astragalus polysaccharide protects formaldehyde-induced toxicity by promoting NER pathway in bone marrow mesenchymal stem cells

Introduction. In our previous study, it has been confirmed that formaldehyde (FA) not only inhibits the proliferative activity, but also causes DNA-protein crosslinks (DPCs) formation in bone marrow mesenchymal stem cells (BMSCs). The purpose of this study was to detect the protective effect of astragalus polysaccharide (APS) against the cytotoxicity and genotoxicity of BMSCs exposed to FA, and to explore potential molecular mechanisms of APS activity. Material and methods. Human BMSCs were cultured in vitro and randomly divided into control cells (Ctrl group), FA-treated cells (FA group, 120 mu mol/L), and cells incubated with FA and increasing concentrations (40, 100, or 400 mu g/mL) of APS (FA + APS groups). Cytotoxicity was measured by MTT assay. DNA strand breakage, DNA-protein crosslinks (DPCs), and micronucleus formation were respectively detected by comet assay, KCl-SDS precipitation assay, and micronucleus assay. The mRNA and protein expression level of xeroderma pigmentosum group A (XPA), xeroderma pigmentosum group C (XPC), excision repair cross-complementation group 1 (ERCC1), replication protein A1 (RPA1), and replication protein A2 (RPA2) were all detected by qRT-PCR and Western Blot. Results. Compared with the FA group, the cytotoxicity, DNA strand breakage, DPCs, and micronucleus levels were decreased significantly in FA + APS groups (P < 0.01). Meanwhile, the mRNA and protein expression of XPA, XPC, ERCC1, RPA1, and RPA2 were up-regulated significantly in the FA + APS groups (P < 0.05) with the most prominent effect of the 100 mu g/mL APS. Conclusions. Our results suggest that APS can protect the cytotoxicity and genotoxicity of human BMSCs induced by FA. The mechanism may be associated with up-regulated expression of XPA, XPC, ERCC1, RPA1, and RPA2 in the nucleotide excision repair (NER) pathway which promotes DNA damage repair.

Automated summary

In this study, astragalus polysaccharide (APS) was found to protect human bone marrow mesenchymal stem cells (BMSCs) from the cytotoxicity and genotoxicity induced by formaldehyde (FA). The protective mechanism may involve the upregulation of various genes in the nucleotide excision repair (NER) pathway, which facilitates DNA damage repair.