Department of Zoology, MMV, Banaras Hindu University, Varanasi, 221005, India.
Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
Inflammopharmacology. 2017 Jun;25(3):329-341. doi: 10.1007/s10787-017-0334-3. Epub 2017 Mar 13.
Curcumin (diferuloylmethane), a major component of turmeric is well known for its anti-inflammatory potential. Present study investigates sequential release of inflammatory mediators post LPS challenge (10 mg/kg,i.p.) causing lung inflammation and its modulation by curcumin through different routes (20 mg/kg, i.p and 10 mg/kg, i.n.) in murine model. Dexamethasone (1 mg/kg, i.p) was used as standard drug.
Lung Inflammation was evaluated by histopathological analysis, myeloperoxidase (MPO) activity followed by inflammatory cell count and total protein content measurements in bronchoalveolar fluid (BALF). Reactive oxygen species (ROS), nitrite and TNF-α levels were measured as markers of endotoxin shock at different time points (1-72 h). The mRNA expression of transforming growth factors-β1 (TGF-β1), iNOS and Toll-like receptor-4 (TLR-4) were measured followed by Masson's trichrome staining and hydroxyproline levels as collagen deposition marker leading to fibrotic changes in lungs.
We found that LPS-induced lung inflammation and injury was maximum 24-h post LPS challenge shown by MPO and histological analysis which was further supported by elevated nitrite and ROS levels whereas TNF-α level was highest after 1 h. Endotoxin-induced mortality was significantly reduced in curcumin (i.p) pretreatment groups up to 72-h post LPS challenge. Significant inhibition in mRNA expression of iNOS, TGF-β1 and TNF-α level was noted after curcumin treatment along with lowered MPO activity, inflammatory cell count, ROS, nitrite levels and collagen deposition in lungs.
Our results suggest that higher endotoxin dose causes inflammatory mediator release in chronological order which tend to increase with time and reached maximum after 24-h post-endotoxin (LPS) exposure. Intraperitoneal route of curcumin administration was better in modulating inflammatory mediator release in early phase as compared to intranasal route of administration. It can be used as supplementary therapeutic intervention at early stage of endotoxemia, having fewer side effects.
姜黄素（二芳基甲烷）是姜黄的主要成分，以其抗炎潜力而闻名。本研究通过不同途径（腹腔内 20mg/kg 和鼻内 10mg/kg）研究脂多糖（LPS）（10mg/kg，腹腔内）刺激后炎症介质的顺序释放及其对姜黄素的调节作用，导致肺部炎症在小鼠模型中。地塞米松（1mg/kg，腹腔内）用作标准药物。
通过组织病理学分析、髓过氧化物酶（MPO）活性以及支气管肺泡灌洗液（BALF）中炎症细胞计数和总蛋白含量的测量来评估肺部炎症。在不同时间点（1-72 小时）测量活性氧（ROS）、亚硝酸盐和 TNF-α 水平作为内毒素休克的标志物。测量转化生长因子-β1（TGF-β1）、iNOS 和 Toll 样受体-4（TLR-4）的 mRNA 表达，然后进行 Masson 三色染色和羟脯氨酸水平作为导致肺部纤维化变化的胶原沉积标志物。
我们发现 LPS 诱导的肺部炎症和损伤在 LPS 刺激后 24 小时达到最大值，这一点通过 MPO 和组织学分析得到了证明，这一点进一步得到了升高的亚硝酸盐和 ROS 水平的支持，而 TNF-α 水平在 1 小时后最高。姜黄素（腹腔内）预处理组的内毒素诱导死亡率在 LPS 刺激后 72 小时内显著降低。姜黄素治疗后，iNOS、TGF-β1 和 TNF-α 水平的 mRNA 表达显著抑制，同时 MPO 活性、炎症细胞计数、ROS、亚硝酸盐水平和肺部胶原沉积降低。
我们的结果表明，较高的内毒素剂量按时间顺序释放炎症介质，这些介质随着时间的推移而趋于增加，在接触内毒素（LPS）后 24 小时达到最大值。与鼻内给药途径相比，腹腔内给予姜黄素在调节早期炎症介质释放方面效果更好。它可以作为内毒素血症早期的辅助治疗干预措施，副作用较少。
