Dendrobium Polysaccharides as Anti-Diabetic Agents: Hypoglycemic Mechanisms, and Structure-Activity Relationships.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal Dendrobium species have long been used in Chinese materia medica and ethnomedicinal practices to promote fluid production, nourish yin, clear heat, and relieve thirst. Traditional records of their use for "Xiaoke" provide an ethnopharmacological rationale for investigating the hypoglycemic effects of Dendrobium polysaccharides. AIM OF THE REVIEW: This review summarizes the structural characteristics, hypoglycemic mechanisms, and structure-activity relationships of Dendrobium polysaccharides and critically evaluates the limitations of the available evidence and the barriers to clinical translation. MATERIALS AND METHODS: Relevant literature published between January 1998 and July 2026 was identified by searching the Web of Science Core Collection, Scopus, PubMed, SciFinder-n, and China National Knowledge Infrastructure (CNKI). These searches were supplemented by Google Scholar, reference list screening, and consultation of pharmacopoeias, materia medica, and ethnomedicinal sources. RESULTS: Dendrobium polysaccharides are structurally heterogeneous polymers. Many fractions are enriched in mannose and glucose, and acetylated β-(1→4)-mannans and glucomannans are frequently identified among the active fractions. The reported molecular weights of these compounds vary widely. Although 5-200 kDa is the most commonly reported range for active fractions, higher molecular weight fractions also exhibit activity. Branching patterns and higher-order conformations vary according to the botanical origin and preparation method. Evidence from cell and animal models indicates that these polysaccharides may protect pancreatic β cells, attenuate insulin resistance, regulate glucose and lipid metabolism, reduce oxidative stress and inflammation, and modulate the gut microbiota and intestinal barrier. The activity of these polysaccharides is associated with their monosaccharide composition, glycosidic linkages, molecular weight, O-acetylation, and higher-order conformation. However, most of these associations are based on comparisons across species, fractions, and experimental conditions, preventing the clear distinction of the effects of individual structural features. CONCLUSIONS: Preclinical evidence supports the hypoglycemic potential of Dendrobium polysaccharides via multiple pathways. However, structural heterogeneity, methodological inconsistency, and limited human evidence impede cross-study comparisons and clinical translation. Future research should prioritize standardized preparation and characterization, controlled structure-activity comparisons, additional in vivo efficacy and safety studies, and rigorous clinical validation.