International journal of biological macromolecules · 2026
Immunomodulatory polysaccharides from natural sources: A review focusing on plant, fungal, and algal polysaccharide origins, extraction, mechanisms, and structure-activity relationships.
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Zhang Chen, Guo Yuyan, Bu Gangtao, Fan Chunyan, Li Yanying, Chen Qingshan, Zhang Lili, Kuang Haixue, Liu Yan, Pan Juan
Аннотация
BACKGROUND: The rising incidence of immune-related diseases has increased healthcare expenditures. Currently, conventional drugs are limited by high costs, increased infection risk, off-target effects, and other adverse effects. Natural polysaccharides offer an alternative due to their diverse sources, safety, and remarkable immunomodulatory activities. A systematic review of their sources, extraction methods, mechanisms, and structure-activity relationships is lacking.
SCOPE AND METHODS: This paper reviews the progress in research on natural polysaccharides with immunomodulatory properties, and summarizes their sources (plants, fungi, and algae), extraction technologies (conventional versus emerging green techniques), and immunoregulatory mechanisms (encompassing innate/adaptive immune cells, immune organs, and gut immunity, along with associated signaling networks). Moreover, this paper summarizes the structure-activity relationships of these polysaccharides (including molecular weight, monosaccharide composition, glycan chain structure, chemical modifications, and higher-order conformation). This review synthesizes the literature by searching Web of Science, PubMed, and Scopus (literature search last updated in August 2026), summarizes the progress, and discusses future trends.
CONCLUSIONS: Immunomodulatory polysaccharides are mainly derived from plants, algae, and fungi. They regulate immune cells and organs through multiple signaling pathways, thereby controlling immune responses. Although these polysaccharides are diverse, some exhibit specific structure-activity relationships. This review synthesizes structure and activity from various source polysaccharides, elucidates their complex regulatory mechanisms, and summarizes the structure-activity relationships. Despite significant advances in research on the structure and activity of polysaccharides, conformational analysis of polysaccharides in the physiological environment, the application of artificial intelligence in the optimization of green extraction processes, and clinical transformation still need to advance.
SCOPE AND METHODS: This paper reviews the progress in research on natural polysaccharides with immunomodulatory properties, and summarizes their sources (plants, fungi, and algae), extraction technologies (conventional versus emerging green techniques), and immunoregulatory mechanisms (encompassing innate/adaptive immune cells, immune organs, and gut immunity, along with associated signaling networks). Moreover, this paper summarizes the structure-activity relationships of these polysaccharides (including molecular weight, monosaccharide composition, glycan chain structure, chemical modifications, and higher-order conformation). This review synthesizes the literature by searching Web of Science, PubMed, and Scopus (literature search last updated in August 2026), summarizes the progress, and discusses future trends.
CONCLUSIONS: Immunomodulatory polysaccharides are mainly derived from plants, algae, and fungi. They regulate immune cells and organs through multiple signaling pathways, thereby controlling immune responses. Although these polysaccharides are diverse, some exhibit specific structure-activity relationships. This review synthesizes structure and activity from various source polysaccharides, elucidates their complex regulatory mechanisms, and summarizes the structure-activity relationships. Despite significant advances in research on the structure and activity of polysaccharides, conformational analysis of polysaccharides in the physiological environment, the application of artificial intelligence in the optimization of green extraction processes, and clinical transformation still need to advance.