Tetrandrine ameliorates dextran-sulfate-sodium-induced colitis in mice through inhibition of nuclear factor -kappaB activation

Int J Colorectal Dis. 2009 Jan;24(1):5-12. doi: 10.1007/s00384-008-0544-7. Epub 2008 Aug 7.

Abstract

Background: Activation of nuclear factor (NF)-kappaB has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC), and tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to be a potent inhibitor of NF-kappaB activation. The purpose of the study was to investigate effects of tetrandrine on experimental model of UC.

Materials and methods: Tetrandrine was administered in experimental colitis induced by dextran sulfate sodium (DSS). The disease activity index (DAI) and histological score were observed. NF-kappaB DNA binding activity was assessed by electrophoretic mobility shift assay. The expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.

Results: A significant improvement was observed in DAI and histological score in mice with tetrandrine, and the increase in NF-kappaB DNA binding activity, myeloperoxidase activity, IL-1beta, and TNF-alpha in mice with DSS-induced colitis was significantly reduced following administration of tetrandrine.

Conclusion: The administration of tetrandrine leads to an amelioration of DSS-induced colitis, suggesting administration of tetrandrine may provide a therapeutic approach for UC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylisoquinolines / pharmacology*
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / pathology*
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / antagonists & inhibitors*
  • Peroxidase / drug effects
  • Peroxidase / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Benzylisoquinolines
  • Immunosuppressive Agents
  • Interleukin-1beta
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • tetrandrine
  • Dextran Sulfate
  • Peroxidase