Comparative Respiratory Protective Effects of Auricularia auricula Polysaccharide Fractions: From Antioxidant-Dependent Antitussive Effects to Microbiota-Associated Anti-Asthmatic Activity

As an edible and medicinal fungus, Auricularia auricula contains polysaccharides (AAPs) as its primary bioactive components. The molecular weight (Mw) of these macromolecules is recognized as a critical determinant of their bioavailability and physiological effects. However, systematic comparative studies on the respiratory protective effects of AAPs with Mws are still limited. In this study, two AAPs with distinct Mws (1554 kDa and 31 kDa) were prepared and characterized, and their antitussive, expectorant, and anti-asthmatic activities were evaluated. The results revealed that the two AAPs exhibited different monosaccharide compositions. Compared with AAPs-H (1554 kDa), AAPs-L (31 kDa) showed superior in vitro antioxidant activity, better solubility, and lower viscosity. Furthermore, AAPs-L improved redox profiles (SOD, GSH-Px, MDA) and reduced substance P release to 2.17 pg/mL, thereby attenuating the cascade of pro-inflammatory mediators. Consequently, mice treated with 200 mg/kg BW AAPs-L exhibited a significant reduction in cough frequency and prolonged cough incubation period. In contrast, AAPs-H, with its higher Mw and mannose content (50.24%), exerted unique anti-asthmatic effects by restoring Th1/Th2 immune balance, modulating the NF-κB signaling pathway, and reshaping the gut microbiota, as evidenced by an increased abundance of Cryptobacteroides sp900546395. And both AAPs promoted phenol red excretion, indicating expectorant effects. This study comprehensively evaluated and compared the differential protective effects of AAPs with distinct Mws on the respiratory system in mice, providing a new perspective for the functional food application and comprehensive utilization of Mw-tailored AAPs.