Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer.
Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer.
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DOI：
10.1016/j.biomaterials.2016.06.018
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发表时间：
2016-09
期刊：
影响因子：
14
通讯作者：
Merlin D
中科院分区：
文献类型：
--
作者：
Zhang M;Viennois E;Prasad M;Zhang Y;Wang L;Zhang Z;Han MK;Xiao B;Xu C;Srinivasan S;Merlin D
临床需要新的、更有效的治疗慢性和衰弱性炎症性肠病（IBD）的方法，包括克罗恩病和溃疡性结肠炎。在这项研究中，我们对从食用姜中提取的特定纳米颗粒（GDNPs 2）进行了表征，并证明了它们在口服后的结肠靶向性。GDNPs 2的平均尺寸为~230 nm，具有负zeta电位。这些纳米颗粒含有高水平的脂质，少量蛋白质，约125个microrna (mirna)，以及大量的生姜生物活性成分（6-姜辣素和6-姜酚）。我们还证明GDNPs 2主要被肠上皮细胞（IECs）和巨噬细胞吸收，并且无毒。通过使用不同的小鼠结肠炎模型，我们发现GDNPs 2可以减少急性结肠炎，增强肠道修复，并预防慢性结肠炎和结肠炎相关癌症（CAC）。2D-DIGE/MS分析进一步确定了GDNPs 2参与这些小鼠模型的分子候选靶点。口服GDNPs 2可提高结肠炎模型IECs的存活和增殖，降低促炎因子（TNF-α、IL-6和IL-1β），升高抗炎因子（IL-10和IL-22），提示GDNPs 2具有在促进愈合的同时减轻损伤因素的潜力。综上所述，从食用姜中提取的纳米颗粒GDNPs 2代表了一种改善IBD预防和治疗的新型天然递送机制，并具有克服合成纳米颗粒常见的潜在毒性和生产规模有限等局限性的额外优势。
There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. In this study, we characterized a specific population of nanoparticles derived from edible ginger (GDNPs 2) and demonstrated their efficient colon targeting following oral administration. GDNPs 2 had an average size of ~230 nm and exhibited a negative zeta potential. These nanoparticles contained high levels of lipids, a few proteins, ~125 microRNAs (miRNAs), and large amounts of ginger bioactive constituents (6-gingerol and 6-shogaol). We also demonstrated that GDNPs 2 were mainly taken up by intestinal epithelial cells (IECs) and macrophages, and were nontoxic. Using different mouse colitis models, we showed that GDNPs 2 reduced acute colitis, enhanced intestinal repair, and prevented chronic colitis and colitis-associated cancer (CAC). 2D-DIGE/MS analyses further identified molecular target candidates of GDNPs 2 involved in these mouse models. Oral administration of GDNPs 2 increased the survival and proliferation of IECs and reduced the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), and increased the anti-inflammatory cytokines (IL-10 and IL-22) in colitis models, suggesting that GDNPs 2 has the potential to attenuate damaging factors while promoting the healing effect. In conclusion, GDNPs 2, nanoparticles derived from edible ginger, represent a novel, natural delivery mechanism for improving IBD prevention and treatment with an added benefit of overcoming limitations such as potential toxicity and limited production scale that are common with synthetic nanoparticles.