Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, PR China.
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, PR China; Research Centre for Model Organisms, Shanghai, PR China.
Biomaterials. 2015;53:475-83. doi: 10.1016/j.biomaterials.2015.02.116. Epub 2015 Mar 20.
Sepsis is a significant public healthcare problem, affecting millions of people worldwide each year, killing one in four, and increasing in incidence. Thus, advanced therapeutic strategies are required to treat sepsis patients. Curcumin (Cur) is a promising anti-inflammatory agent for various inflammatory disorders. However, the therapeutic efficacy of Cur is limited due to poor aqueous solubility, rapid degradation, and low bioavailability. The aims of this study were to evaluate the therapeutic potential of Cur-loaded solid lipid nanoparticles (Cur-SLNs) for sepsis treatment. A firefly luciferase transgenic mouse was used to monitor real time interleukin 1β (IL-1β) expression in lipopolysaccharide (LPS)-induced sepsis model to examine the protective effect of Cur-SLNs, and to elucidate its underlying molecular mechanisms. Mice (female or male) were intraperitoneally administered with free Cur or Cur-SLNs (30 mg/kg) before the intraperitoneal delivery of LPS (3 mg/kg). Our results indicated that Cur-SLNs can effectively reduced levels of IL-1β expression compared to free Cur, especially at 3 h after LPS injection. Also, Cur-SLNs significantly decreased the expression of serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β as compared with free Cur, but augmented anti-inflammatory cytokine IL-10 by ELISA assay. Further, marked alleviation of the sepsis-induced damage to organs, including kidney, liver, and heart was observed with Cur-SLNs treatment as determined by hematoxylin/eosin-staining. Western blot analyses revealed that Cur-SLNs can significantly lower the expression levels of TLR4, TLR2, and TNF-α in lymph node tissues. Meanwhile, it showed suppressions of NF-κB activation and IκBα degradation levels. In conclusion, we suggested that Cur-SLNs may be used as an effective and safe therapeutic agent in treating sepsis in high-risk patient groups.
脓毒症是一个重大的公共卫生问题，每年影响全球数百万人，致死率高达四分之一，且发病率呈上升趋势。因此，需要先进的治疗策略来治疗脓毒症患者。姜黄素（Cur）是一种有前途的抗炎药物，可用于治疗各种炎症性疾病。然而，由于其水溶性差、降解快、生物利用度低，Cur 的治疗效果受到限制。本研究旨在评估载姜黄素固体脂质纳米粒（Cur-SLNs）治疗脓毒症的治疗潜力。利用萤火虫荧光素酶转基因小鼠实时监测脂多糖（LPS）诱导的脓毒症模型中白细胞介素 1β（IL-1β）的表达，以研究 Cur-SLNs 的保护作用，并阐明其潜在的分子机制。雌性或雄性小鼠在腹腔内给予 LPS（3mg/kg）前，分别腹腔内给予游离姜黄素或 Cur-SLNs（30mg/kg）。结果表明，与游离姜黄素相比，Cur-SLNs 能有效降低 LPS 诱导的脓毒症小鼠模型中 IL-1β的表达水平，尤其是在 LPS 注射后 3 小时。此外，与游离姜黄素相比，Cur-SLNs 还能显著降低血清促炎细胞因子 IL-6、TNF-α 和 IL-1β的表达，但通过 ELISA 检测发现抗炎细胞因子 IL-10 增加。同时，Cur-SLNs 治疗还能显著减轻脓毒症引起的肾、肝、心等器官损伤，通过苏木精/伊红染色法进行组织病理学评估。Western blot 分析表明，Cur-SLNs 能显著降低淋巴结组织中 TLR4、TLR2 和 TNF-α 的表达水平，同时抑制 NF-κB 的激活和 IκBα 的降解。综上所述，我们认为 Cur-SLNs 可作为一种治疗高危人群脓毒症的有效、安全的治疗药物。
