Shen-Qi-Ling extract alleviates spleen deficiency syndrome in mice: insights into the gut microbiota–metabolite axis and PI3K/Akt/NF-κB/AQP3 signaling pathway

SQLE is a potential functional food for alleviating spleen deficiency syndrome. • SQLE contains diverse bioactive compounds with flavonoids as major components. • SQLE restores gut microbiota homeostasis and promotes SCFAs production. • SQLE improves spleen deficiency via the PI3K/Akt/NF-κB/AQP3 signaling pathway. Spleen deficiency syndrome (SDS) manifests as impaired digestive function, fatigue, and metabolic issues, which are closely associated with dysbiosis of the gut microbiota. Shen-Qi-Ling extract (SQLE) is a natural extract prepared from food-medicine homologous resources, primarily consisting of Codonopsis pilosula , Astragalus membranaceus , and Poria cocos . However, the bioactive constituents and mechanisms by which it alleviates SDS remain unclear. In this study, we systematically characterized the chemical constituents of SQLE and elucidated its potential mechanisms of action against SDS in mice. Using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) analysis, 137 compounds were identified in SQLE, with flavonoids being the most abundant, followed by coumarins, phenylpropanoids, and organic acids. Molecular docking analysis indicated that SQLE might have a spleen-strengthening effect. Treatment with SQLE, particularly SQLE-M, significantly enhanced intestinal absorption, exercise performance, tissue damage, and oxidative stress. Moreover, SQLE-M restored gut microbial homeostasis, increased the relative abundance of potentially beneficial bacteria, and promoted the production of short-chain fatty acids (SCFAs). Notably, SQLE-M normalized the intestinal barrier dysfunction and metabolic disorders by activating the PI3K/Akt signaling pathway, inhibiting NF-κB-mediated inflammatory responses, and upregulating aquaporin 3 (AQP3) expression. Collectively, SQLE mitigates SDS, which may be associated with alterations in the gut microbiota-metabolite axis and the PI3K/Akt/NF-κB/AQP3 signaling pathway, offering new perspectives for developing spleen-strengthening functional foods derived from food-medicine homologous resources. Download: Download high-res image (462KB) Download: Download full-size image