Curcumin ameliorates ethanol and nonethanol experimental pancreatitis
Curcumin ameliorates ethanol and nonethanol experimental pancreatitis
复制标题
DOI：
10.1152/ajpgi.00138.2002
复制
发表时间：
2003-01-01
影响因子：
4.5
通讯作者：
Pandol, SJ
中科院分区：
文献类型：
--
作者：
Gukovsky, I;Reyes, CN;Pandol, SJ
治疗胰腺炎的方法是有限的。转录因子NF-kappaB是炎症分子表达的关键调节因子，它的激活是实验性胰腺炎的早期事件，并与炎症反应相关。我们在此报道，姜黄素，一种已知抑制核因子-kappaB和激活蛋白(AP)-1的天然植物化学物质，另一种重要的促炎转录因子，改善了两种大鼠模型的胰腺炎。在由酒精饮食和低剂量CCK联合诱导的蓝蛋白胰腺炎和胰腺炎中，姜黄素通过一系列参数(组织学、血清淀粉酶、胰腺胰蛋白酶和中性粒细胞浸润)改善了疾病的严重程度。通过DNA结合和抑制IkappaB蛋白的降解，以及对胰腺中细胞因子IL-6和TNF-α、趋化因子KC和诱导型一氧化氮合酶的mRNAs的诱导，姜黄素显著抑制了NF-kappaB和AP-1的激活。姜黄素还可阻断CCK诱导的胰腺腺泡核转录因子-kappaB和AP-1的活化。我们的发现表明，阻断炎症反应的关键信号可以缓解酒精和非酒精模型中的胰腺炎。他们建议，目前正在进行癌症预防临床试验的姜黄素，可能对治疗胰腺炎有用。
Treatments for pancreatitis are limited. Activation of transcription factor NF-kappaB, a key regulator of inflammatory molecule expression, is an early event in experimental pancreatitis and correlates with the inflammatory response. We report here that curcumin, a natural phytochemical known to inhibit NF-kappaB and activator protein (AP)-1, another important proinflammatory transcription factor, ameliorates pancreatitis in two rat models. In both cerulein pancreatitis and pancreatitis induced by a combination of ethanol diet and low-dose CCK, curcumin improved the severity of the disease as measured by a number of parameters (histology, serum amylase, pancreatic trypsin, and neutrophil infiltration). Curcumin markedly inhibited NF-kappaB and AP-1 activation, assessed by DNA binding and degradation of inhibitory IkappaB proteins, and the induction of mRNAs for cytokines IL-6 and TNF-alpha, the chemokine KC, and inducible nitric oxide synthase in pancreas. Curcumin also blocked CCK-induced NF-kappaB and AP-1 activation in isolated pancreatic acini. Our findings indicate that blocking key signals of the inflammatory response ameliorates pancreatitis in both ethanol and nonethanol models. They suggest that curcumin, which is currently in clinical trials for cancer prevention, may be useful for treatment of pancreatitis.