Xu Zhang

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.

Mannatide, a glycopeptide derived from the fermentation of α-hemolytic Streptococcus, exhibits diverse immunomodulatory activity. However, clinical evidence regarding its efficacy in colitis remains limited, and its underlying mechanisms are poorly understood. In this study, mannatide was produced via submerged fermentation of α-hemolytic Streptococcus, yielding a concentration of 0.15 mg/mL in the fermentation broth and a molecular weight of 57,401 Da as determined by HPGPC-RID. The effects of mannatide on DSS-induced colitis in mice were also evaluated. The results demonstrated that mannatide alleviated clinical symptoms including weight loss and colon shortening, mitigated pathological damage such as mucosal epithelial disruption and inflammatory cell infiltration, and reduced histological scores from 4.56 to below 2. Additionally, it improved redox profiles by increasing SOD activity to 1.8 times that of the model group at a dosage of 50 mg/kg/BW. Mechanistically, mannatide mediated PI3K/Akt, which was involved in the pathogenesis of colitis in mice through multidirectional transcriptional regulation, including mediating the NF-κB pathway to reduce inflammation, regulating Th17/Treg immune homeostasis, and engaging Akt/eNOS for intestinal mucosal protection. Furthermore, mannatide at 50 mg/kg/BW upregulated the abundance of CAG-485, Muribaculum, and Alistipes-A, affecting P221-PWY, FAO-PWY, REDCITCYC, and PWY-6590 and other colitis-related metabolic pathways via altering gut microbiota composition, ultimately alleviating colitis in mice. Thus, this study provided a foundation for utilizing α-hemolytic Streptococcus and mannatide, as well as offered mechanistic insights for optimizing colitis treatment.