Abstract
Rehmannia glutinosa polysaccharides (RGPs) are recognized for their diverse pharmacological potential. However, their translation into practical applications faces significant hurdles. The primary challenges include their intrinsic structural complexity, poor oral bioavailability, and poorly defined structure-activity relationships (SAR). This review highlights that RGPs, as complex heteropolysaccharides, exhibit diverse bioactivities including immunomodulation, anti-inflammatory, antitumor, anti-aging, and metabolic regulation. Innovative green extraction techniques enhance yield and preserve bioactivity compared to conventional methods. Structural analyses reveal that molecular weight (MW), monosaccharide composition, and glycosidic linkages critically influence functions. Chemical modifications and nano-delivery systems improve solubility, bioavailability, and targeted delivery. Pharmacological studies show RGPs modulate gut microbiota, increasing short-chain fatty acid production, which mediates systemic benefits. However, clinical application requires addressing batch variability, scalability, and the lack of human trials. Future research should focus on precise structural elucidation, quantitative structure-activity models, and smart formulations to advance RGPs as therapeutics and functional foods in precision medicine.