ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Translational Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1610711
This article is part of the Research TopicAdvancements in Bioactive Nanomaterials for Disease ManagementView all articles
Hydroxyethyl Starch-Curcumin Nanoparticles Ameliorate DSS-Induced Ulcerative Colitis in Mice via Synergistic TLR4/NF-κB Suppression, Nrf2 Activation, Intestinal Barrier Restoration, and Gut Microbiota Modulation
Provisionally accepted
Sheng Li1
Shiyi Lu2Jiahui Xiong1Liang Chen1Yanting Lin1Xiaohui Chen2Xinyi Wang2Lijing Lin2Xiaoliang Cai1Xiaoyu Yang1*- 1Fuzhou Hospital of Traditional Chinese Medicine, Fuzhou, China
- 2Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China
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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.
Keywords: Curcumin, ulcerative colitis, Gut Microbiota, TLR4/NF-κB, Nrf2
Received: 12 Apr 2025; Accepted: 24 Jun 2025.
Copyright: © 2025 Li, Lu, Xiong, Chen, Lin, Chen, Wang, Lin, Cai and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoyu Yang, Fuzhou Hospital of Traditional Chinese Medicine, Fuzhou, China
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