INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Donglei Zheng,Lulu Ma,Xiaojuan Xin,Ying Gao,Shijian Dong,Ying Huang,Jijun Wu,Jiaying Huo,Shugang Li
Ovotransferrin (OVT), a bioactive protein from egg white, has been demonstrated to exhibit anti-inflammatory efficacy and suppress the progression of ulcerative colitis. Nevertheless, its role in preserving intestinal barrier integrity has not been reported. This study investigated the role of OVT on intestinal barrier dysfunction in DSS-induced ulcerative colitis mice and its underlying mechanisms. OVT significantly attenuated the severity of intestinal barrier injury, reduced inflammatory infiltration, and restored goblet cell density (Model: 5.00 goblet cells/crypt, High: 12.75 goblet cells/crypt) alongside the expression of MUC2 (87.64 %), ZO-1 (83.98 %), and Occludin (74.93 %). Concurrently, OVT decreased intestinal permeability by 84.42 %. Furthermore, OVT downregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), while elevating anti-inflammatory IL-10 levels and restoring redox homeostasis. RNA-seq and Western blot analysis revealed that OVT inhibited the PI3K-Akt/MAPK pathway by decreasing the phosphorylation of p85α (31.73 %), Akt (69.59 %), p38 (25.00 %), and ERK (41.18 %). Metabolomics showed that OVT modulated key metabolites, including L-glutamate, serotonin, and d -fructose-6-phosphate, while decreasing glucose and L-asparagine. These results suggested that OVT regulated immune responses and metabolic pathways, highlighting its therapeutic potential in preserving intestinal barrier integrity.
研究领域:
分子生物学
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免疫学
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药理学
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生物化学
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细胞生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Sheng Li,Shiyi Lu,Jiahui Xiong,Liang Chen,Yanting Lin,Xiaohui Chen,Xinyi Wang,Lijing Lin,Xiaoliang Cai,Xiaoyu Yang
Here, we systematically evaluated the therapeutic efficacy and mechanisms of action of in-house synthesized hydroxyethyl starch-curcumin nanoparticles (HES-CUR NPs) in ulcerative colitis (UC). Using a dextran sodium sulfate (DSS)-induced UC mouse model, we analyzed the effect of HES-CUR NPs on colonic tissue and the gut microbiota through the assessment of organ indices and serum biochemical markers, histopathology, immunohistochemistry, Western blot, and 16S rRNA sequencing. We found that HES-CUR NPs significantly suppressed the TLR4/NF-κB inflammatory pathway (downregulated TLR4, p-IKKβ, IL-1β, IL-6, NFKB, MyD88, and p-IKKB/IKKB; p < 0.01), activated the Nrf2/HO-1 antioxidant pathway (enhanced Nrf2 nuclear translocation and HO-1 expression), and upregulated the expression of tight junction proteins (claudin-1, occludin, ZO-1), thereby restoring intestinal barrier integrity. Microbiota analysis revealed that HES-CUR NPs increased gut microbiota diversity (elevated Chao1, Shannon, and ACE indices) and enriched beneficial bacteria abundance (Ligilactobacillus murinus, Lactobacillus johnsonii). Antibiotic intervention partially attenuated the therapeutic effects of the HES-CUR NPs, confirming that their effects involved microbiota-dependent mechanisms. Compared to CUR and SASP, HES-CUR NPs exhibited significantly enhanced bioavailability and efficacy (p < 0.01), attributed to the targeted delivery and sustained-release properties of the hydroxyethyl starch nanocarrier. No toxicity was observed, as indicated by normal spleen, liver, and thymus indices and stable levels of TP, ALT, AST, ALB, GLB, and ALB/GLB. Our findings indicated that HES-CUR alleviates UC through a synergistic, multi-target mechanism involving inflammatory pathway suppression, antioxidant pathway activation, intestinal barrier repair, and microbiota modulation, providing a theoretical foundation for developing efficient and safe natural nanomedicines targeting UC.
研究领域:
纳米医学
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胃肠病学
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免疫学
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药理学
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微生物学
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分子生物学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Ming Wu,Hongrui Ping,Kun Wang,Hui Ding,Meng Zhang,Ziqiong Yang,Qian Du
The oral delivery of anti-inflammatory drugs has been a promising strategy for enhancing the clinical efficacy of ulcerative colitis (UC) treatment strategies. However, achieving site specific drug delivery to colon tissues and target cells is a challenging task for formulation scientists. In this study, macrophages-targeted liposome-loaded pectin-chitosan hydrogels were developed for UC treatment via oral administration. Folate-functionalized cholesterol was synthesized as lipid membrane materials for the liposomes containing curcumin (CUR). The incorporation of the liposomal CUR within pectin-chitosan hydrogels resulted in a matrix that exhibited considerable sensitivity to colonic enzymes during in vitro release. The targeted delivery of hybrids was able to effectively reach macrophages. They also showed enhanced capability to downregulate TNF-α, IL-6, and IL-1β in the lipopolysaccharide-induced Raw 264.7 cells model. DSS-induced mice model showed improved anti-UC effects, including accelerated mucosal repair and decreased inflammation and modulate the immune balance in the intestinal tissue of mice with colitis, which may be attributable to increased drug accumulation in the colonic lumen and improved internalization to target cells. Therefore, the incorporation of folate-modified liposomes containing CUR and pectin-chitosan physical hydrogels could potentially serve as a favorable approach for treating UC through an oral colon-targeted drug delivery system.
研究领域:
药学
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药物递送系统
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炎症
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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