Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education) (Y.Z., X.Li, Q.Z., J.L., J.J., N.D., X.Liu, X.C., F.C., C.X., M.U.B., Y.L., B.Y.), and Institute of Cardiovascular Research (Y.Z., Y.L., B.Y.), Harbin Medical University, Harbin, Heilongjiang, China; and Department of Bone Surgery (L.Y.) and Department of General Surgery (Y.W.), the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
J Pharmacol Exp Ther. 2014 Jun;349(3):417-26. doi: 10.1124/jpet.114.212795. Epub 2014 Mar 27.
Intestinal adhesion, characterized by connection of the loops of the intestine with other abdominal organs by fibrous tissue bands, remains an inevitable event of abdominal operations and can cause a number of complications. Berberine hydrochloride (berberine), a natural plant alkaloid derived from Chinese herbal medicine, is characterized by diverse pharmacological effects, such as anticancer and lower elevated blood glucose. This study is designed to investigate the effects of berberine on adhesion and inflammation after abdominal surgeries and the underlying molecular mechanisms. Adhesion severity grades and collagen deposition were assessed 14 days after surgery. We evaluated the levels of intercellular adhesion molecule-1 (ICAM-1) and inflammatory cytokines interleukin-1β (IL-1β), IL-6, transforming growth factor β (TGF-β), tumor necrosis factor-α (TNF-α), and examined transforming growth factor-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor κB (NF-κB) signaling. The surgery group experienced the most severe adhesions, and berberine strikingly reduced the density and severity of adhesion. Results showed significant lower expression of IL-1β, IL-6, TGF-β, TNF-α, and ICAM-1, in berberine groups compared with the operation group. Activities of phosphorylated JNK and phosphorylated NF-κB were inhibited in the berberine groups compared with the surgery group. Our novel findings identified berberine hydrochloride as a promising strategy to prevent adhesion by downregulating ICAM-1 and reduce inflammation by inhibiting the TAK1/JNK and TAK1/NF-κB signaling after abdominal surgery, which brought out a good therapeutic approach for the development of clinical application for postoperative abdominal adhesion and inflammation.
肠粘连是一种由纤维组织带将肠环与其他腹部器官连接的病症,它仍然是腹部手术不可避免的事件,并可能导致许多并发症。盐酸小檗碱(黄连素)是一种从中药中提取的天然植物生物碱,具有多种药理作用,如抗癌和降低血糖升高。本研究旨在探讨黄连素对腹部手术后粘连和炎症的影响及其潜在的分子机制。术后 14 天评估粘连严重程度和胶原沉积。我们评估了细胞间黏附分子-1(ICAM-1)和炎症细胞因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、转化生长因子-β(TGF-β)、肿瘤坏死因子-α(TNF-α)的水平,并检查了转化生长因子激活激酶 1(TAK1)/c-Jun N 末端激酶(JNK)和 TAK1/核因子 κB(NF-κB)信号通路。手术组的粘连最严重,而黄连素显著降低了粘连的密度和严重程度。结果表明,与手术组相比,黄连素组的 IL-1β、IL-6、TGF-β、TNF-α和 ICAM-1 的表达显著降低。与手术组相比,黄连素组的磷酸化 JNK 和磷酸化 NF-κB 活性受到抑制。我们的新发现表明,盐酸小檗碱通过下调 ICAM-1 并通过抑制 TAK1/JNK 和 TAK1/NF-κB 信号通路来预防腹部手术后的粘连和炎症,这为腹部手术后粘连和炎症的临床应用提供了一种有前途的治疗方法。