灵芝孢子油-姜黄素纳米乳的制备及其对溃疡性结肠炎的治疗作用

Preparation of Ganoderma lucidum spore oil curcumin nanoemulsions and its therapeutic effect on ulcerative colitis

摘要:

目的 制备灵芝孢子油－姜黄素纳米乳（GLSO@CUR NEs），探讨其对溃疡性结肠炎（UC）的治疗作 用。方法 以吐温80、无水乙醇、灵芝孢子油和姜黄素为主要原料，制备GLSO@CUR NEs。采用透射电镜（TEM） 观察纳米颗粒的形貌尺寸，马尔文粒度分析仪测试粒径及Zeta电位，拉曼光谱表征纳米体系中灵芝孢子油特征化 学结构，红外光谱表征纳米体系的化学成键，同时分析其在不同生理条件下的稳定性。建立 5% 葡聚糖硫酸钠 （DSS）诱导的UC小鼠模型，从结肠长度、体质量、疾病活动指数（DAI）、结肠病理学组织改变、肠道屏障功能方面观 察 GLSO@CUR NEs对 UC小鼠的治疗作用。结果 GLSO@CUR NEs具有流动性和良好的稳定性，液滴形状，大 小均匀。在 DSS 所致的 UC 小鼠模型中，GLSO@CUR NEs 可显著改善结肠损伤，包括缓解身体质量降低、降低 DAI、恢复小鼠结肠长度、改善结肠组织病理学损伤（P < 0.05）；还可抑制DSS诱导的肠道肿瘤坏死因子-α（TNF-α） 产生，上调细胞因子白介素-4（IL-4）、白介素-10（IL-10）、转化生长因子-β1（TGF-β1）及分泌型免疫球蛋白A（SIgA） 水平，降低血清 D-乳酸水平（P < 0.05），改善肠道屏障功能。结论 成功制备 GLSO@CUR NEs，其对 DSS 所致的 UC具有明显的治疗作用。

Abstract:

Objective Preparation of Ganoderma lucidum spore oil-curcumin nanoemulsions (GLSO@CUR NEs) and explore its therapeutic effect on ulcerative colitis (UC). Methods GLSO@CUR NEs were formulated, consisting of Tween 80, anhydrous ethanol, spore oil and curcumin were developed. The morphology and size of GLSO@CUR NEs were observed by using transmission electron microscope (TEM). Malvern particle size analyzer was used to test nanoparticles size and Zeta potential. The characteristic chemical structure of Ganoderma spore oil in nano systems was analyzed by using Raman spectroscopy. The chemical bonding in NEs was determined by infrared spectroscopy. And the stability of GLSO@CUR NEs was analyzed under different physiological conditions. The protective effect on UC was explored in mice with UC induced by 5% dextran sodium sulfate (DSS). The therapeutic effects of GLSO@CUR NEs on UC mice were observed from several aspects, including colon length, body weight, disease activity index (DAI), colon pathological tissue changes, and intestinal barrier function. Results The developed GLSO@CUR NEs had multiple decreasing the DAI, restoring colon length, and improving histological damage (P < 0.05). In addition, GLSO@CUR NEs improved intestinal barrier function by inhibiting DSS induced TNF- α (tumor necrosis factor-alpha) production, upregulating IL-4 (interleukin-4), IL-10 (interleukin-10), TGF-β1 (transforming growth factor-β1) and SIgA (secretory IgA) levels, reducing serum D-lactate levels (P < 0.05). Conclusion A nanoparticle formulation, GLSO@CUR NEs, was successfully developed and shown to possess therapeutic efficacy against DSS-induced UC beneficial properties, including fluidity and excellent stability, and the droplets were uniform in shape and size. In the DSS induced UC mice, GLSO@CUR NEs significantly ameliorated colon injury, including increasing body weight,