Open Access

Protection against ulcerative colitis and colorectal cancer by evodiamine via anti‑inflammatory effects

  • Authors:
    • Yongfeng Zhang
    • Yaqin Zhang
    • Yang Zhao
    • Wanyue Wu
    • Weiqi Meng
    • Yulin Zhou
    • Ye Qiu
    • Chenliang Li
  • View Affiliations

  • Published online on: March 29, 2022     https://doi.org/10.3892/mmr.2022.12704
  • Article Number: 188
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Evodiamine (Evo) is an alkaloid that can be extracted from the berry fruit Evodia rutaecarpa and has been reported to exert various pharmacological effects, such as antidiarrheal, antiemetic and antiulcer effects. In vivo, the potential effects of Evo were investigated in a mouse model of dextran sodium sulfate (DSS)‑induced ulcerative colitis (UC) and in adenomatous polyposis coli (Apc)MinC/Gpt C57BL/6 mice with colorectal cancer (CRC), where the latter harbours a point‑mutation in the Apc gene. Evo suppressed the degree of weight loss and colon shortening induced by DSS, decreased the disease activity index value and ameliorated the pathological alterations in the colon of mice with UC as examined via H&E staining of colon tissues. In addition, Evo decreased the number and size of colonic tumors in ApcMinC/Gpt mice. Proteomics (colon tissues), ELISA (colon tissues and serum) and western blotting (colon tissues) results revealed that Evo inhibited NF‑κB to mediate the levels of various cytokines, including, in the DSS‑induced UC model, IL‑1β, IL‑2, IL‑6, IL‑8, TNF‑α, IFN‑γ (ELISA of colon tissues and serum), NF‑κB, IKKα+β, IκBα, S100a9, TLR4 and MyD88 (western blotting of colon tissues), and, in the colorectal cancer model, IL‑1β, IL‑2, IL‑6, IL‑15, IL‑17, IL‑22, TNF‑α (ELISA of colon tissues and serum), NF‑κB, IKKα+β, IκBα and S100a9 (western blotting of colon tissues), to achieve its anti‑inflammatory and antitumor effects. In vitro, Evo also reduced the viability of the colon cancer cell line SW480, inhibited mitochondrial membrane potential (MMP detection), caused G2/M‑phase arrest (cell cycle detection) and suppressed the translocation of phosphorylated‑NF‑κB from the cytoplasm into the nucleus (immunofluorescence of p‑NF‑κB). Theoretical evidence (MD simulations) suggest that Evo may bind to the ordered domain (α‑helix) of NF‑κB to influence this protein. The protein secondary structure changes were analyzed by the cpptraj module in Amber. In addition, these data provide experimental evidence that Evo may be an effective agent for treating UC and CRC.
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May-2022
Volume 25 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Zhang Y, Zhang Y, Zhao Y, Wu W, Meng W, Zhou Y, Qiu Y and Li C: Protection against ulcerative colitis and colorectal cancer by evodiamine via anti‑inflammatory effects. Mol Med Rep 25: 188, 2022
APA
Zhang, Y., Zhang, Y., Zhao, Y., Wu, W., Meng, W., Zhou, Y. ... Li, C. (2022). Protection against ulcerative colitis and colorectal cancer by evodiamine via anti‑inflammatory effects. Molecular Medicine Reports, 25, 188. https://doi.org/10.3892/mmr.2022.12704
MLA
Zhang, Y., Zhang, Y., Zhao, Y., Wu, W., Meng, W., Zhou, Y., Qiu, Y., Li, C."Protection against ulcerative colitis and colorectal cancer by evodiamine via anti‑inflammatory effects". Molecular Medicine Reports 25.5 (2022): 188.
Chicago
Zhang, Y., Zhang, Y., Zhao, Y., Wu, W., Meng, W., Zhou, Y., Qiu, Y., Li, C."Protection against ulcerative colitis and colorectal cancer by evodiamine via anti‑inflammatory effects". Molecular Medicine Reports 25, no. 5 (2022): 188. https://doi.org/10.3892/mmr.2022.12704