Reprogrammed Epigenetic Landscape-Prophesied Functions of Bioactive Polysaccharides in Alleviating Diseases: A Pilot Study of DNA Methylome Remodeling in Astragalus Polysaccharide (APS)-Improved Osteoporosis in a Rat Model.

DNA methylation is an epigenetic event that plays critical roles in the pathogenesis, progression, and treatment of human diseases. In this study, we investigated the epigenetic mechanisms for Astragalus polysaccharide (APS)-improved osteoporosis in a rat model. The results showed that APS significantly changed the DNA methylome in colonic epithelia with great efficiency. Gene set enrichment analysis (GSEA) based on differentially methylated sites (DMSs) revealed that APS caused promoter DNA methylation changes of genes associated with calcium homeostasis, osteoclast/osteoblast balance, Wnt signaling, and hormone-related processes. Further analysis showed high consistency of APS-induced gene methylomic changes in colonic epithelia and its effects on diabetes, virus infection, and wound healing, which had been reported already. Moreover, we suggested new functions and the involved mechanisms of APS in heart disease, neurological disorder, reproductive problem, and olfactory dysfunction. In this study, we offered epigenetic mechanisms for APS-improved osteoporosis. More importantly, we proposed and proved a reliable method to explore the beneficial effects of bioactive polysaccharides by studying DNA methylation changes at nonfocal sites. We firmly believed the promising prospects of this method for its great efficiency, rapidness, and economy in exploring possible beneficial or therapeutic effects of functional macromolecules with one single experiment.