The chemical composition of the ethanol extract of Acanthopanax senticosus fruit (ASFEE) was systematically characterized using UPLC-MS/MS (Q Exactive Orbitrap), leading to the identification of 45 compounds. Through integrated network pharmacology and molecular docking analyses, the binding affinities between key bioactive constituents—such as eleutheroside E (EE) and quercetin—and core therapeutic targets were predicted and validated. A total of 125 overlapping targets were identified between ASFEE and acute kidney injury (AKI), with significant enrichment observed in critical signaling pathways, including NF-κB, IL-17, and PI3K-Akt. To evaluate the protective effects of ASFEE, both in vitro (HK-2 cells) and in vivo (murine) models of cisplatin (DDP)-induced AKI were employed. Parameters assessed included cell viability, apoptosis, reactive oxygen species (ROS) production, activation of the NF-κB signaling pathway, kidney function, histopathological alterations, and levels of inflammatory cytokines. ASFEE treatment markedly enhanced HK-2 cell viability and reduced cellular apoptosis and ROS generation. In the murine model, DDP administration resulted in significantly elevated serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Both low- and high-dose ASFEE treatments significantly attenuated these increases, improved overall kidney function, and alleviated kidney tubular damage. Furthermore, ASFEE reduced serum levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Multi-omics integration analysis enabled the identification of differentially expressed genes and metabolites. ASFEE was found to reverse 4689 DDP-induced gene expression changes and 323 metabolic disturbances, with the uridine diphosphate glucuronosyltransferase (UGT)-mediated ascorbic acid metabolism pathway emerging as the central regulatory axis. Key candidate genes and proteins were further validated via real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. DDP significantly upregulated the expression of inflammatory markers and associated signaling molecules in kidney tissues, while concurrently downregulating UGT family genes and the UGT1A1 protein involved in uronic acid metabolism. Notably, ASFEE treatment effectively counteracted these alterations, confirming its role in enhancing UGT1A1-mediated metabolic processes and suppressing the NF-κB/PI3K-Akt/IL-17 signaling cascade. These mechanisms contribute to improved antioxidant capacity, mitigation of inflammatory responses, and restoration of metabolic homeostasis, thereby conferring protection against DDP-induced AKI. ASFEE exerts a protective effect on AKI caused by DDP by enhancing antioxidant capacity, inhibiting inflammation and restoring metabolic homeostasis, providing an experimental basis for its subsequent development and application.

Chronic stress induces behavioral abnormalities through coordinated neuroendocrine, inflammatory, oxidative, metabolic, and gut microbial disturbances. Plant-derived volatile fractions may modulate stress-related neurobehavioral responses, yet their antioxidant and anti-inflammatory effects and associated neurobiological mechanisms remain insufficiently characterized. In this study, Ginkgo biloba leaf essential oil (GbO) was extracted from air-dried leaves by hydrodistillation, chemically characterized by GC–MS, and evaluated in a chronic unpredictable mild stress (CUMS) mouse model using behavioral, biochemical, molecular, hippocampal metabolomic, and gut microbiota analyses. HS-SPME–GC–MS tentatively identified 70 volatile constituents detected in at least two independent extraction batches, including 65 constituents consistently detected. In CUMS mice, inhaled GbO, particularly at the higher exposure level, attenuated depression- and anxiety-like behavioral abnormalities without altering general locomotor activity. GbO reduced serum corticosterone and peripheral and hippocampal pro-inflammatory cytokines, alleviated hippocampal oxidative imbalance, and decreased Iba-1 and GFAP signals. These changes were accompanied by reduced NF-κB activation, enhanced Nrf2/HO-1-related antioxidant signaling, and improved BDNF/TrkB/CREB-related neurotrophic signaling and PSD95-associated synaptic integrity. Hippocampal metabolomics further showed partial correction of stress-associated disturbances in neurotransmitter, lipid, inflammatory, and energy/redox metabolism, while 16S rRNA sequencing revealed partial restoration of gut microbial diversity and community structure. Collectively, these findings indicate that inhaled GbO exerts antioxidant and anti-inflammatory effects in CUMS mice in association with coordinated neuroimmune, neurotrophic, metabolic, and gut microbial remodeling.

Although euscaphic acid (EA)—the main active component of Rosa roxburghii Tratt fruit—possesses potential antioxidant, anti-inflammatory, and intestinal protective effects, the mechanisms underlying these properties remain unclear. This study aimed to investigate whether EA can alleviate dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) through multiple mechanisms such as inhibiting oxidative stress, regulating inflammation, remodeling the gut microbiota, and restoring metabolic disturbances. Using a DSS-induced mouse model of UC and integrating histopathological examination, Western blotting, 16S rRNA sequencing, untargeted metabolomics, transcriptome sequencing, and fecal microbiota transplantation, EA’s mechanisms of action were investigated at multiple levels, including the tissue, microbial, and metabolic levels. EA counteracted DSS-induced alterations in MPO, SOD, MDA, IL-6, IL-1β, and TNF-α. In addition, EA intervention improved UC and reversed the reduction in Bacteroides uniformis (B. uniformis) in UC mice. Further studies confirmed that B. uniformis is a key species mediating the UC-alleviating effects of EA. Metabolomics analysis indicated that EA could mitigate the effects of metabolic disorders; transcriptomic analysis indicated that it inhibits inflammatory signaling pathways; and multi-omics analysis further revealed that it alleviates UC by restoring the gut microbiota and correcting metabolic disorders while simultaneously inhibiting oxidative and pro-inflammatory pathways.