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Bioactive substances derived from natural products are valued for effective health-related activities. As extremely important component of plants, animal cell membrane and microbes cytoderm, polysaccharides have been applied as medications, foods and cosmetics stemming from their prominent biological functions and minor side-effects. Recent studies indicate that polysaccharides exert biological effects also through epigenetic mechanism. Through the intervention of DNA methylation, histone modification, and non-coding RNA, polysaccharides