Mechanisms and structure-activity relationships of natural polysaccharides as potential anti-osteoporosis agents: A review

In recent years, polysaccharides derived from natural sources have garnered significant attention due to their safety and potential anti-osteoporotic effects. This review provides a comprehensive overview of the sources, distribution, structures, and mechanisms of anti-osteoporosis polysaccharides, as well as an investigation into their structure-activity relationships. Over thirty distinct, homogenous polysaccharides with anti-osteoporosis properties have been extracted from natural sources, primarily categorized as glucans, fructans, galactomannans, glucomannans, and various other heteropolysaccharides. Natural polysaccharides can effectively enhance osteoblast differentiation and mineralization while suppressing osteoclast activation, with the mechanism regulated by the BMP/SMAD/RUNX2, Wnt/Catenin, OPG/RANKL/RANK, and TLR2/NF-κB/NFATc1 signaling pathways. Furthermore, polysaccharides contribute to the prevention of osteoporosis by mitigating oxidative stress, decreasing inflammation, and modulating the gut microbiota. This review also summarizes the relationship between the monosaccharide composition, molecular weight, and glycosidic bond type of polysaccharides and their anti-osteoporotic activity. A comprehensive summary and analysis of the existing deficiencies and challenges in the research of anti-osteoporotic polysaccharides is also concluded. This review may serve as a significant reference for the discovery and utilization of naturally derived anti-osteoporotic polysaccharides in the pharmaceutical and health industries.