Dendrobium huoshanense Ameliorates Sleep Deprivation-Induced Ileal Mucus Barrier Dysfunction by Regulating Steroid Hormone Biosynthesis and the HPA Axis in Rats

Background/Objectives: Sleep deprivation (SD) induces the accumulation of reactive oxygen species (ROS) in the intestine, causing inflammation in the intestine, thereby damaging the intestinal epithelial barrier function. As a traditional Chinese medicine, Dendrobium huoshanense (DHS) modulates intestinal flora, maintains the intestinal mucosal barrier, and promotes gastrointestinal motility and digestive secretion. However, the role and mechanism of DHS in improving SD-induced intestinal injury have not been fully studied. Methods: The SD model was established by subjecting rats to complete SD using a specialised SD instrument. Hematoxylin and eosin (HE) staining was performed to evaluate pathological injury in ileal tissues. Enzyme-linked immunosorbent assay (ELISA) and biochemical methods were used to quantify the main inflammatory cytokines, oxidative stress markers, and hypothalamic–pituitary–adrenal (HPA) axis activity. The expression levels of E-cadherin and Occludin proteins in the ileum tissue were analyzed by Western blotting. Additionally, the pH value of ileal mucus, unit secretion, water content, and dry matter weight were measured. Differential metabolites in rat ileum mucus were profiled using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Results: DHS alleviated the pathological injury of the ileum induced by SD. DHS reduced the levels of serotonin (5-HT), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), while increasing interleukin-10 (IL-10) levels, thereby attenuating systemic inflammatory responses. Furthermore, DHS decreased malondialdehyde (MDA) content and elevated glutathione (GSH) and superoxide dismutase (SOD) levels in ileal tissues. DHS also upregulated the protein expression of E-cadherin and Occludin in intestinal tissues. In addition, DHS decreased the pH of ileal mucus, promoted intestinal mucus secretion, and increased dry matter content, facilitating the restoration of the mucus barrier. DHS may alleviate SD-induced ileal injury by modulating steroid hormone biosynthesis. DHS decreased the levels of adrenocorticotropic hormone (ACTH), cortisol (CORT), and corticotropin-releasing hormone (CRH), indicating that DHS suppresses the abnormal activation of the hypothalamic–pituitary–adrenal (HPA) axis. Conclusions: In this study, a comprehensive multi-index evaluation showed that DHS could significantly improve the ileal injury caused by SD in rats. The mechanism involved regulating the balance of serum neurotransmitters and inflammatory factors, reducing oxidative stress in tissues, and improving the physicochemical properties of intestinal mucus. Metabolomic analysis further revealed that these protective effects may be mediated via the regulation of steroid hormone biosynthesis pathways and are associated with the inhibition of abnormal HPA axis activation.