Aims: Neuroinflammation, microglial activation, and oxidative stress contribute to neuropsychiatric deficits following spinal cord injury (SCI). Hyperbaric oxygen (HBO) therapy has demonstrated anti‐inflammatory, antioxidant, and neuroprotective properties. This study aimed to investigate the therapeutic effects and underlying mechanisms of HBO on depressive‐like behavior, cognitive impairment, and hippocampal pathology in a rat model of SCI.Methods: We employed a battery of behavioral assessments, unbiased stereological analysis, immunofluorescence staining, and biochemical assays to evaluate neuroinflammation, oxidative stress, mitochondrial damage, and iron accumulation in the hippocampus. Untargeted proteomic analysis was conducted to identify potential molecular targets of HBO. Western blotting was used to assess the activation of the Nrf2/GPX4 signaling pathway. ML385, a selective Nrf2 inhibitor, was intrathecally administered 30 min prior to daily HBO treatment to validate pathway involvement.Results: HBO treatment significantly alleviated depressive‐like behavior and cognitive deficits in SCI rats. It also suppressed M1‐type microglial activation and reduced hippocampal neuroinflammation. Additionally, HBO mitigated neuronal ferroptosis induced by SCI through activation of the Nrf2/GPX4 signaling pathway. The protective effects of HBO were abolished by coadministration of ML385, confirming the critical role of Nrf2 signaling in mediating its anti‐ferroptosis effects.Conclusion: These findings highlight ferroptosis as a key pathological mechanism in SCI‐induced hippocampal damage and suggest that HBO therapy alleviates depressive‐like behavior and cognitive impairment by targeting the Nrf2/GPX4 pathway. This study provides new insights into the therapeutic potential of HBO in managing SCI‐related neuropsychiatric dysfunction.

JOURNAL/nrgr/04.03/01300535-202511000-00034/figure1/v/2026-04-24T022020Z/r/image-tiff Previous studies have shown that the compound ( E )-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one (D30), a pyromeconic acid derivative, possesses antioxidant and anti-inflammatory properties, inhibits amyloid-β aggregation, and alleviates scopolamine-induced cognitive impairment, similar to the phase III clinical drug resveratrol. In this study, we established a mouse model of Alzheimer’s disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β–induced neuropathology. Our results showed that D30 alleviated fibrillar amyloid-β–induced cognitive impairment, promoted fibrillar amyloid-β clearance from the hippocampus and cortex, suppressed oxidative stress, and inhibited activation of microglia and astrocytes. D30 also reversed the fibrillar amyloid-β–induced loss of dendritic spines and synaptic protein expression. Notably, we demonstrated that exogenous fibrillar amyloid-β introduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain, and this increase was blocked by D30. Considering the role of D30 in clearing amyloid-β, inhibiting neuroinflammation, protecting synapses, and improving cognition, this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer’s disease.

The kojic acid dimer (KAD) is a metabolite derived from developing cottonseed when contaminated with aflatoxin. The KAD has been shown to exhibit bright greenish-yellow fluorescence, but little else is known about its biological activity. In this study, using kojic acid as a raw material, we developed a four-step synthetic route that achieved the gram-scale preparation of the KAD in approximately 25% total yield. The structure of the KAD was verified by single-crystal X-ray diffraction. The KAD showed good safety in a variety of cells and had a good protective effect in SH-SY5Y cells. At concentrations lower than 50 μM, the KAD was superior to vitamin C in ABTS⁺ free radical scavenging assay; the KAD resisted the production of reactive oxygen species induced by H₂O₂ as confirmed by fluorescence microscopy observation and flow cytometry analysis. Notably, the KAD could enhance the superoxide dismutase activity, which might be the mechanism of its antioxidant activity. The KAD also moderately inhibited the deposition of amyloid-β (Aβ) and selectively chelated Cu²⁺, Zn²⁺, Fe²⁺, Fe³⁺, and Al³⁺, which are related to the progress of Alzheimer's disease. Based on its good effects in terms of oxidative stress, neuroprotection, inhibition of Aβ deposition, and metal accumulation, the KAD shows potential for the multi-target treatment of Alzheimer's disease.

Colitis is a global health challenge that severely impairs quality of life, necessitating effective dietary interventions. This study investigated the protective effects of Ganoderma lucidum triterpenoids (GLTs) on pathological symptoms, inflammatory responses, and gut microbiota dysbiosis in a dextran sulfate sodium (DSS)-induced murine model. Our results demonstrated that GLT intervention significantly attenuated the disease activity index (DAI), prevented colon shortening, and fortified gut barrier integrity through upregulating the transcription of tight junction proteins. GLT inhibited the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and bolstered antioxidant defenses (CAT) by controlling the TLR4/NF-κB pathway and upregulating the Nrf2 pathway. Furthermore, 16S rRNA sequencing and non-targeted metabolomics revealed that GLT reshaped the gut microbial landscape (enriching Enterorhabdus and Lachnospiraceae NK4A136 group) and reconfigured amino acid metabolism to restore colonic homeostasis. Collectively, these findings highlight the potential of GLT as a functional food ingredient to prevent colitis, potentially linked to the modulation of the microbiota–metabolite–immune interplay, offering a novel nutritional strategy for inflammatory bowel disease management.

Ganoderma is a highly valued medicinal fungus, especially in Traditional Chinese Medicine (TCM). A formulation of Ganoderma lucidum spore oil and aqueous extracts from the fruiting bodies of Ganoderma lucidum and Ganoderma sinense (G2SO) has been developed as a functional formulation proposed to support immune function and tumor control. The aim of this study was to evaluate the antitumor activity and immunomodulatory effects of G2SO in mice. A tumor-bearing mouse model was established using 4T1 cells in BALB/c mice for antitumor evaluation. Immunomodulatory outcomes were evaluated in ICR mice after 30 days of oral administration. The results showed that the inhibition rate of G2SO on 4T1 tumors in the tumor-bearing mice was 35.31 ± 9.51%. Moreover, G2SO produced small but statistically significant enhancements of innate immune function in mice, including natural killer (NK) cell cytotoxicity and macrophage phagocytosis. Indices of adaptive immunity (hemolysin production and ConA-induced T-cell proliferation) were also increased, whereas LPS-stimulated cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in RAW264.7 cells showed downward tendencies that were largely not significant. Overall, G2SO exhibits modest immunomodulatory activity together with measurable antitumor efficacy in vivo within the limits of the study design. These findings support further preclinical and clinical evaluation of G2SO as a functional formulation to support cancer prevention and immunomodulation.