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口服姜黄衍生的具有抗炎和促解决生物活性的外体样纳米囊泡治疗小鼠结肠炎。

Oral administration of turmeric-derived exosome-like nanovesicles with anti-inflammatory and pro-resolving bioactions for murine colitis therapy.

机构信息

School of Basic Medical Sciences, Xi'an Key Laboratory of Immune Related Diseases, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

出版信息

J Nanobiotechnology. 2022 Apr 29;20(1):206. doi: 10.1186/s12951-022-01421-w.

Abstract

BACKGROUND

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing and remitting course. The current therapeutics are only modestly effective and carry risks for unacceptable adverse events, and thus more effective approaches to treat UC is clinically needed.

RESULTS

For this purpose, turmeric-derived nanoparticles with a specific population (TDNPs 2) were characterized, and their targeting ability and therapeutic effects against colitis were investigated systematically. The hydrodynamic size of TDNPs 2 was around 178 nm, and the zeta potential was negative (- 21.7 mV). Mass spectrometry identified TDNPs 2 containing high levels of lipids and proteins. Notably, curcumin, the bioactive constituent of turmeric, was evidenced in TDNPs 2. In lipopolysaccharide (LPS)-induced acute inflammation, TDNPs 2 showed excellent anti-inflammatory and antioxidant properties. In mice colitis models, we demonstrated that orally administrated of TDNPs 2 could ameliorate mice colitis and accelerate colitis resolution via regulating the expression of the pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and antioxidant gene, HO-1. Results obtained from transgenic mice with NF-κB-RE-Luc indicated that TDNPs 2-mediated inactivation of the NF-κB pathway might partially contribute to the protective effect of these particles against colitis.

CONCLUSION

Our results suggest that TDNPs 2 from edible turmeric represent a novel, natural colon-targeting therapeutics that may prevent colitis and promote wound repair in colitis while outperforming artificial nanoparticles in terms of low toxicity and ease of large-scale production.

摘要

背景

溃疡性结肠炎(UC)是一种炎症性肠病(IBD),其特征为结肠黏膜弥漫性炎症和反复发作缓解。目前的治疗方法仅略有疗效,并存在不可接受的不良反应风险,因此临床上需要更有效的方法来治疗 UC。

结果

为此,我们对姜黄衍生的具有特定群体的纳米颗粒(TDNPs 2)进行了表征,并系统地研究了其针对结肠炎的靶向能力和治疗效果。TDNPs 2 的水动力学直径约为 178nm,zeta 电位为负(-21.7mV)。质谱鉴定 TDNPs 2 含有高水平的脂质和蛋白质。值得注意的是,姜黄中的生物活性成分姜黄素存在于 TDNPs 2 中。在脂多糖(LPS)诱导的急性炎症中,TDNPs 2 表现出优异的抗炎和抗氧化特性。在小鼠结肠炎模型中,我们证明口服给予 TDNPs 2 可以通过调节促炎细胞因子(包括 TNF-α、IL-6 和 IL-1β)和抗氧化基因 HO-1 的表达来改善小鼠结肠炎并加速结肠炎的缓解。来自 NF-κB-RE-Luc 转基因小鼠的结果表明,TDNPs 2 介导的 NF-κB 通路失活可能部分有助于这些颗粒对结肠炎的保护作用。

结论

我们的结果表明,来自食用姜黄的 TDNPs 2 代表了一种新型的天然结肠靶向治疗方法,可预防结肠炎并促进结肠炎愈合,同时在低毒性和易于大规模生产方面优于人工纳米颗粒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7af2/9052603/5ee32693968e/12951_2022_1421_Fig1_HTML.jpg

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