Jian Zhang

Inflammatory bowel disease (IBD) in older individuals is characterized by immune senescence and deteriorating intestinal homeostasis, both of which limit the efficacy of current therapies. Here, we develop fluorinated β‐glucan/pectin nanogels (F ₂ ‐Ast@NGs) for oral delivery of astilbin, a natural flavonoid with anti‐inflammatory and immunoregulatory activities. This multifunctional platform integrates gastrointestinal protection, colon‐targeted release, and local immune modulation. The β‐glucan shell preserves nanogel stability during upper gastrointestinal transit while enabling β‐glucanase‐responsive disassembly in the colon. Fluorocarbon segments enhance mucus penetration, and the pectin matrix prolongs colonic retention, promoting drug accumulation at inflamed sites. In aged mice with dextran sulfate sodium (DSS)‐induced colitis, F ₂ ‐Ast@NGs alleviate disease severity, attenuate senescence‐associated features of colonic CD4 ⁺ T cells, and enhance Foxp3 ⁺ regulatory T cell (T _reg ) responses. Concurrently, the β‐glucan/pectin nanogel matrix contributes to increased short‐chain fatty acid production and favorable alterations in gut microbial composition. Notably, the therapeutic efficacy of F ₂ ‐Ast@NGs is markedly attenuated in Foxp3 ⁺ T _reg ‐depleted mice, supporting an important role for T _reg ‐mediated immunoregulation. Collectively, F ₂ ‐Ast@NGs enable precise colonic delivery while coordinately remodeling the intestinal immune and microbial microenvironment, providing a promising oral nanotherapeutic strategy for colitis in aged hosts.

Da-Yuan-Yin Decoction (DYY), used since the early Qing Dynasty in China for damp-heat syndrome, was evaluated for its comprehensive protective effects. Rats received a high-fat/high-sugar diet for 14 days, then daily exposure to high temperature/humidity (31.0 ± 0.5°C, 85%-95%) for 10 hours over 14 days. Damp-heat syndrome was induced on day 29 via intraperitoneal lipopolysaccharide (LPS) injections (1 mg/kg and 0.5 mg/kg after 4 hours). Two hours post-modeling, rats received DYY (400 or 800 mg/kg/day) orally for 5 days. Symptoms were scored. On day 33, kidney, spleen, tongue, lung, liver, stomach, and colon tissues underwent histopathological and immunochemical/immunofluorescence analysis. Serum levels of inflammation factors, C-reactive protein (CRP), cell-free DNA (cfDNA), myeloperoxidase (MPO), and superoxide dismutase (SOD) were quantified. Complete blood count (CBC), blood biochemistry, short-chain fatty acids (SCFAs), gut microbiota composition in the colon, and metabolites in the cecum were analyzed. DYY significantly reduced symptom scores and decreased CRP level, while also regulating parameters in CBC and biochemical profiles. The treatment ameliorated tissue damage in the kidney, spleen, tongue, lung, liver, stomach, and colon. DYY downregulated citrullinated histone H3 (Cit H3), polyclonal peptidylarginine deiminase 4 (PADI4), and MPO expressions in the lung, stomach, and colon. Furthermore, it modulated inflammatory responses, suppressed the interleukin-23 (IL-23)/janus kinase-2 (JAK2)/signal transduction and transcription activator-3 (STAT3) signaling pathway and enhanced antioxidant activity. DYY administration significantly increased total SCFA content. The intervention restored gut microbiota diversity and abundance, while ameliorating metabolic dysregulation. Systemic pathophysiological alterations were observed in rats with damp-heat syndrome. The comprehensive protective effects of DYY involved suppression of neutrophil extracellular traps (NETs) formation through downregulation of PADI4 expression, modulation of inflammatory responses, inhibition of the IL-23/JAK2/STAT3 signaling pathway, restoration of intestinal microecological balance and metabolic homeostasis, and enhancement of antioxidant.

Background and Aim: Kui‐Jie‐Ling capsule (Kui‐Jie‐Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui‐Jie‐Ling and Kui‐Jie‐Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS). Methods: Network pharmacology was combined with an animal experiment to reveal the targets of Kui‐Jie‐Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7 days. On the second day, the mice in the Kui‐Jie‐Ling group were orally administered with Kui‐Jie‐Ling (1.5 and 3.0 g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui‐Jie‐Ling (3.0 g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short‐chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments. Results: The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui‐Jie‐Ling alleviated UC via multi‐pathway. Kui‐Jie‐Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide–toll‐like receptor 4/nuclear factor kappa B and interleukin‐23–Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis. Conclusion: These studies provided the experimental basis for the clinical administration of Kui‐Jie‐Ling and Kui‐Jie‐Ling combined with adalimumab against UC.