Advances in research on natural polysaccharides in the treatment of acute lung injury

Acute lung injury (ALI) is a critical respiratory disorder that severely endangers public health. As natural macromolecular active compounds with outstanding biosafety and negligible toxic side effects, natural polysaccharides exhibit prominent development potential in the field of anti-ALI pharmacological research. This review finds that natural polysaccharides with ALI activity mostly possess a molecular weight below 20 kDa, and core monosaccharide residues mainly include glucose, galactose, mannose, rhamnose and galacturonic acid, and the predominant polysaccharide types are rhamnogalacturonan-I as well as neutral polysaccharides rich in glucose and galactose. Moreover, this review aims to systematically delineate the core molecular mechanisms underlying the anti-ALI efficacy of natural polysaccharides. These mechanisms principally involve multiple interconnected signaling pathways, including suppression of the TLR4/NF-κB/MAPK cascade, modulation of antioxidant stress responses, regulation of the Treg/Th17 immune balance, inhibition of the NLRP3/caspase-1/GSDMD pyroptosis axis, attenuation of complement system hyperactivation, and restoration of gut microbiota homeostasis along with associated metabolite, etc. In addition, structural modification of some polysaccharides via processing, hydrolysis can significantly enhance the effect of anti-ALI. This review aims to provide a scientific basis for mechanistic studies, structural optimization, and new anti-ALI drug development, and to guide precise clinical treatment of ALI.