Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids. Kaempferol (Kae) is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone (Dex) induced muscle atrophy in animals has not been elucidated. To explore this issue, the present experiments used a computationally assisted drug design scheme combining network pharmacology, molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy. Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy, with a total of 228 cross-targets for Kae and muscle atrophy. GO and KEGG analyses were performed based on the protein-protein interaction (PPI) network of muscle atrophy and Kae component targets. The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species, and the response to oxidative stress; the cellular components were mainly focused on membrane microdomains, and membrane regions; the molecular functions mainly worked on phosphatase binding; and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy. Finally, as verified by in vivo experiments, Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/mTOR/signalling pathway, inhibiting Foxo1/Foxo3 activity, and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and MuRF1; Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway, enhances muscle antioxidant capacity, inhibits the release of COX-2 and TNF-α inflammatory factors, and reduces the damage caused by oxidative stress and inflammatory factors to muscles. Therefore, there may be a synergistic effect of PI3K/AKT/mTOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy. The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations, implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.

Boletus aereus have biological effects such as anti-inflammatory, antioxidant and immunomodulatory effects. As medicines and functional foods, Boletus aereus has a long history of application. In order to explore the immunomodulatory mechanism of Boletus aereus polysaccharide (BAP) in the intestinal tract, the present study was conducted to construct a mouse model of colitis induced by LPS, and the preventive mechanism of Boletus aereus extract on LPS-induced intestinal inflammation in rats was analyzed by histopathological examination and biochemical analysis. Meanwhile, the immunomodulatory mechanisms were analyzed in combination with metabolomics and gut microbiomics. We found that BAP effectively reduced the levels of pro-inflammatory factors IL-6 and TNF-α and increased the levels of anti-inflammatory factor IL-10 in the serum of mice, and BAP suppressed the expression of TLR4/NF-ĸB/MAPK inflammatory signaling pathway in the colonic tissues, inhibited the expression of inflammatory vesicle NRLP3, and promoted the expression of NRF2/HO-1 signaling pathway, and elevated the SOD, T- AOC, and T-AOC levels. BAP decreased the expression of the TGF/Smad signaling pathway and decreased the expression of the fibrosis factors Collagen I Collagen III, α-SMA. The results indicated that Boletus edulis extract may exert immunomodulatory function by inhibiting TLR4/NF-ĸB/MAPK signaling pathway,and enhance the anti-oxidative stress ability by promoting the expression of NRF2/HO-1 signaling pathway. BAP altered the composition of gut microbiota in LPS-induced mice. In addition, Spearman's correlation coefficient showed a significant correlation between serum tyrosine metabolic pathway and gut microbiota species. The changes in gut microbiota and serum metabolites may partially explain the protective effect of BAP against colitis. In conclusion, these results suggest that BAP may be involved in the prevention of colitis disease at multiple levels, and also provide a theoretical basis for the development of Boletus aereus as an adjunctive functional edible for enteropathy.