Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan.
J Surg Res. 2011 Nov;171(1):199-204. doi: 10.1016/j.jss.2010.01.007. Epub 2010 Feb 4.
Systemic inflammatory response syndromes involving sepsis continue to have extremely high mortality rates. Inflammation is difficult to control when it spreads throughout the body and often progresses into multiple organ dysfunction, eventually leading to death. Cepharanthine (CE) is a plant alkaloid that possesses bioactive properties, with various known actions. In the present study, we investigated protective effects of CE in a lipopolysaccharide (LPS)-induced systemic inflammatory response model and examined underlying mechanisms.
We intravenously administered LPS (7.5 mg/kg) to male Wistar rats after intraperitoneal injections of either physiologic saline (LPS group) or CE (10 mg/kg; CE + LPS group), or 2 h before intraperitoneal injection of CE (post-CE + LPS group). We then compared changes in serum cytokine and nitrogen oxide levels over time, and performed histologic examinations of the lungs and liver in each group. Using mouse macrophage RAW264.7 cells, we determined the effect of CE on LPS-induced cytokine secretion into the cell culture medium, as well as NF-κB activity.
The increase in LPS-induced cytokine levels in rat serum was significantly inhibited by CE treatment; this effect was also seen in the post-CE + LPS group. In addition, we observed histologic improvements with CE co-treatment. In vitro, CE inhibited NF-κB activation by inhibiting the IKK pathway.
These results suggest that CE exerts protective effects, at least in part, via NF-κB inhibition. CE may thus be a potential agent for treating systemic inflammatory response syndromes such as sepsis.
涉及脓毒症的全身性炎症反应综合征仍然具有极高的死亡率。炎症在全身扩散时很难控制，并且经常进展为多器官功能障碍，最终导致死亡。石蒜碱（CE）是一种具有生物活性的植物生物碱，具有多种已知作用。在本研究中，我们研究了 CE 在脂多糖（LPS）诱导的全身性炎症反应模型中的保护作用，并探讨了其潜在机制。
我们在雄性 Wistar 大鼠腹膜内注射生理盐（LPS 组）或 CE（10 mg/kg；CE + LPS 组）后，静脉内给予 LPS（7.5 mg/kg），或在腹膜内注射 CE 前 2 小时给予 CE（后 CE + LPS 组）。然后，我们比较了各组血清细胞因子和氮氧化物水平随时间的变化，并对各组肺和肝组织进行了组织学检查。我们使用小鼠巨噬细胞 RAW264.7 细胞，确定了 CE 对 LPS 诱导的细胞培养上清液中细胞因子分泌以及 NF-κB 活性的影响。
CE 处理显著抑制了 LPS 诱导的大鼠血清细胞因子水平的升高；后 CE + LPS 组也观察到了这种作用。此外，我们观察到 CE 共同治疗的组织学改善。体外，CE 通过抑制 IKK 途径抑制 NF-κB 激活。
这些结果表明，CE 通过抑制 NF-κB 发挥保护作用。因此，CE 可能是治疗全身性炎症反应综合征（如脓毒症）的潜在药物。
