一种基于紫草素的自组装纳米药物通过涉及HDC相关组胺调控和肠道菌群调节缓解DSS诱导的结肠炎
A shikonin-based self-assembled nanomedicine alleviates DSS-induced colitis involving HDC-associated histamine regulation and gut microbiota modulation.
摘要(中文译文)
溃疡性结肠炎（UC）是一种以反复发作为特征的慢性肠道炎症性疾病。目前的治疗方法疗效有限且存在安全性问题。本研究旨在通过开发新型金属-酚类纳米颗粒来提高天然化合物紫草素的水溶性并增强其治疗效果。通过将Zn与紫草素配位并用聚乙二醇（PEG）对复合物进行功能化，合成了Zn-紫草素-PEG杂化纳米颗粒（Zn-SHK-PEG NPs）。采用葡聚糖硫酸钠（DSS）诱导的结肠炎模型评估该纳米颗粒的治疗潜力和机制。Zn-SHK-PEG NPs治疗显著减轻了体重下降和结肠缩短，降低了疾病活动指数（DAI），并减少了组织病理学损伤。机制研究表明，该纳米颗粒降低了组氨酸脱羧酶（HDC）表达，这与PKM2调控相关，并伴随组胺（HA）水平降低和炎症抑制。此外，Zn-SHK-PEG NPs改变了肠道微生物群组成，包括富集，这也可能有助于整体治疗效果。总之，Zn-SHK-PEG NPs改善了DSS诱导的结肠炎，其治疗效果与调控HDC/组胺轴、抑制炎症反应和调节肠道微生物群相关。这些发现表明Zn-SHK-PEG NPs可能代表一种治疗溃疡性结肠炎的潜在策略。
Abstract
Ulcerative colitis (UC) is a chronic inflammatory disorder of the intestine characterized by recurrent episodes. Current therapies exhibit limited efficacy and raise safety concerns. This study aimed to enhance the water solubility of the natural compound shikonin and improve its therapeutic efficacy by developing novel metal-phenolic nanoparticles. Zn-shikonin-PEG hybrid nanoparticles (Zn-SHK-PEG NPs) were synthesized by coordinating Zn with shikonin and functionalizing the complex with polyethylene glycol (PEG). Dextran sulfate sodium (DSS)-induced colitis was employed to evaluate the therapeutic potential and mechanisms of the nanoparticles. Treatment with Zn-SHK-PEG NPs markedly alleviated weight loss and colon shortening, decreased the disease activity index (DAI), and reduced histopathological injury. Mechanistic investigations suggested that the nanoparticles reduced histidine decarboxylase (HDC) expression, which was associated with PKM2 regulation, accompanied by decreased histamine (HA) levels and suppressed inflammation. Furthermore, Zn-SHK-PEG NPs altered the gut microbiota composition, including enrichment of , which may also contribute to the overall therapeutic effect. In summary, Zn-SHK-PEG NPs ameliorated DSS-induced colitis, and the therapeutic effects were associated with the regulation of the HDC/histamine axis, suppression of inflammatory responses, and modulation of gut microbiota. These findings suggest that Zn-SHK-PEG NPs may represent a potential strategy for ulcerative colitis treatment.
如何引用
AMA
Wang Zhang, Jingrou Sun, Ying Ou, Jing Zhang, Yilan Bai, Jingxi Hong, et al. A shikonin-based self-assembled nanomedicine alleviates DSS-induced colitis involving HDC-associated histamine regulation and gut microbiota modulation.. Journal of materials chemistry. B. 2026; doi:10.1039/d6tb00517a.
APA
Wang Zhang, Jingrou Sun, Ying Ou, Jing Zhang, Yilan Bai, Jingxi Hong, et al (2026). A shikonin-based self-assembled nanomedicine alleviates DSS-induced colitis involving HDC-associated histamine regulation and gut microbiota modulation.. Journal of materials chemistry. B. https://doi.org/10.1039/d6tb00517a
GB/T 7714
Wang Zhang, Jingrou Sun, Ying Ou, Jing Zhang, Yilan Bai, Jingxi Hong, et al. A shikonin-based self-assembled nanomedicine alleviates DSS-induced colitis involving HDC-associated histamine regulation and gut microbiota modulation.[J]. Journal of materials chemistry. B, 2026 doi:10.1039/d6tb00517a.
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