Berberine inhibits inflammatory mediators and attenuates acute pancreatitis through deactivation of JNK signaling pathways
Berberine inhibits inflammatory mediators and attenuates acute pancreatitis through deactivation of JNK signaling pathways
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DOI：
10.1016/j.molimm.2016.04.011
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发表时间：
2016-06-01
影响因子：
3.6
通讯作者：
Park, Sung-Joo
中科院分区：
文献类型：
--
作者：
Choi, Sun-Bok;Bae, Gi-Sang;Park, Sung-Joo
急性胰腺炎（AP）是一种危及生命的疾病。小檗碱 (BBR) 是一种著名的植物生物碱，据报道在许多疾病中具有抗炎活性。然而，BBR对AP的影响尚未明确阐明。因此，本研究旨在探讨BBR对雨蛙素诱导的小鼠AP的影响。 AP 由雨蛙蛋白或 L-精氨酸诱导。在BBR治疗组中，在第一次注射雨蛙素或L-精氨酸前1小时腹腔内施用BBR。获取血样以确定血清淀粉酶和脂肪酶活性以及一氧化氮的产生。快速切除胰腺和肺以检查组织学变化、髓过氧化物酶（MPO）活性和实时逆转录聚合酶链反应。此外，还评估了BBR的调节机制。用 BBR 治疗小鼠可减少胰腺损伤以及淀粉酶、脂肪酶的活性和胰腺炎相关的肺损伤，并抑制多种炎症参数，例如促炎细胞因子和诱导型一氧化氮合成 (iNOS) 的表达。此外，BBR 给药显着抑制了雨蛙蛋白诱导的 AP 中的 c-Jun N 末端激酶 UNK) 激活。 JNK 失活可改善胰腺炎并抑制炎症介质。这些结果表明，BBR 通过 JNK 失活对轻度和重度急性胰腺炎模型发挥抗炎作用，并且可能成为治疗 AP 的有益靶点。 (C) 2016 Elsevier Ltd. 保留所有权利。
Acute pancreatitis (AP) is a life-threatening disease. Berberine (BBR), a well-known plant alkaloid, is reported to have anti-inflammatory activity in many diseases. However, the effects of BBR on AP have not been clearly elucidated. Therefore, the present study aimed to investigate the effects of BBR on ceruleininduced AP in mice. AP was induced by either cerulein or L-arginine. In the BBR treated group, BBR was administered intraperitoneally 1 h before the first cerulein or L-arginine injection. Blood samples were obtained to determine serum amylase and lipase activities and nitric oxide production. The pancreas and lung were rapidly removed for examination of histologic changes, myeloperoxidase (MPO) activity, and real-time reverse transcription-polymerase chain reaction. Furthermore, the regulating mechanisms of BBR were evaluated. Treatment of mice with BBR reduced pancreatic injury and activities of amylase, lipase, and pancreatitis-associated lung injury, as well as inhibited several inflammatory parameters such as the expression of pro-inflammatory cytokines and inducible nitric oxide synthesis (iNOS). Furthermore, BBR administration significantly inhibited c-Jun N-terminal kinase UNK) activation in the cerulein-induced AP. Deactivation of JNK resulted in amelioration of pancreatitis and the inhibition of inflammatory mediators. These results suggest that BBR exerts anti-inflammatory effects on AP via JNK deactivation on mild and severe acute pancreatitis model, and could be a beneficial target in the management of AP. (C) 2016 Elsevier Ltd. All rights reserved.