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Research ArticleInflammation, Immunopharmacology, and Asthma

Berberine Hydrochloride Prevents Postsurgery Intestinal Adhesion and Inflammation in Rats

Yong Zhang, Xiaoguang Li, Qingwei Zhang, Jiamin Li, Jiaming Ju, Ning Du, Xin Liu, Xiaohui Chen, Feiran Cheng, Lei Yang, Chaoqian Xu, Muhammad U. Bilal, Yunwei Wei, Yanjie Lu and Baofeng Yang
Journal of Pharmacology and Experimental Therapeutics June 2014, 349 (3) 417-426; DOI: https://doi.org/10.1124/jpet.114.212795
Yong Zhang
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
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Xiaoguang Li
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
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Qingwei Zhang
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
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Jiamin Li
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
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Jiaming Ju
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
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Ning Du
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
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Xin Liu
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
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Xiaohui Chen
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
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Feiran Cheng
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
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Lei Yang
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
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Chaoqian Xu
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
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Muhammad U. Bilal
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
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Yunwei Wei
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
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Yanjie Lu
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
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Baofeng Yang
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
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Abstract

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.

Footnotes

    • Received January 3, 2014.
    • Accepted March 26, 2014.
  • Y.Z. and X.Li contributed equally to this work.

  • This work was supported by the Funds for Creative Research Groups [Grant 81121003] and the Major Program [Grant 81130088] of National Natural Science Foundation of China; the National Nature Science Foundation of China [Grants 30901208 and 81270042]; and the Scientific Research Fund of Heilongjiang Provincial Education Department [Grant 11531216].

  • dx.doi.org/10.1124/jpet.114.212795.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 349 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 349, Issue 3
1 Jun 2014
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Research ArticleInflammation, Immunopharmacology, and Asthma

Berberine Prevents Intestinal Adhesion and Inflammation

Yong Zhang, Xiaoguang Li, Qingwei Zhang, Jiamin Li, Jiaming Ju, Ning Du, Xin Liu, Xiaohui Chen, Feiran Cheng, Lei Yang, Chaoqian Xu, Muhammad U. Bilal, Yunwei Wei, Yanjie Lu and Baofeng Yang
Journal of Pharmacology and Experimental Therapeutics June 1, 2014, 349 (3) 417-426; DOI: https://doi.org/10.1124/jpet.114.212795

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Research ArticleInflammation, Immunopharmacology, and Asthma

Berberine Prevents Intestinal Adhesion and Inflammation

Yong Zhang, Xiaoguang Li, Qingwei Zhang, Jiamin Li, Jiaming Ju, Ning Du, Xin Liu, Xiaohui Chen, Feiran Cheng, Lei Yang, Chaoqian Xu, Muhammad U. Bilal, Yunwei Wei, Yanjie Lu and Baofeng Yang
Journal of Pharmacology and Experimental Therapeutics June 1, 2014, 349 (3) 417-426; DOI: https://doi.org/10.1124/jpet.114.212795
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