Open Access

Artesunate exerts protective effects against ulcerative colitis via suppressing Toll‑like receptor 4 and its downstream nuclear factor‑κB signaling pathways

  • Authors:
    • Yu‑Xuan Chen
    • Xiao‑Qi Zhang
    • Cheng‑Gong Yu
    • Shu‑Ling Huang
    • Ying Xie
    • Xiao‑Tan Dou
    • Wen‑Jia Liu
    • Xiao‑Ping Zou
  • View Affiliations

  • Published online on: June 5, 2019     https://doi.org/10.3892/mmr.2019.10345
  • Pages: 1321-1332
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Artesunate (ART) is a semi‑synthetic derivative of artemisinin used in the treatment of patients with malaria, which has also been reported to have immunoregulatory, anticancer and anti‑inflammatory properties. The aim of the present study was to investigate the possible beneficial effects of ART on ulcerative colitis (UC) rats and to detect the possible mechanisms underlying these effects. A UC rat model was established using dextran sulfate sodium (DSS). Rats were randomly divided into the following groups: Normal control, UC model group, UC rats treated with a low, medium or high dose of ART (10, 30 and 50 mg/kg/day, respectively), and the positive control group (50 mg/kg/day 5‑aminosalicylic acid). The damage status of colonic mucosal epithelial tissue was investigated by hematoxylin and eosin staining, and then the weight, colon length and disease activity index (DAI) were measured. Western blotting and reverse transcription‑quantitative polymerase chain reaction analysis were used to detect the levels of cytokines associated with UC and proteins associated with Toll‑like receptor 4 (TLR4)‑nuclear factor (NF)‑κB pathway. ELISA was also performed to measure the levels of inflammatory cytokines. In addition, the viability and infiltration of RAW264.7 cells were examined using Cell Counting Kit‑8 and Transwell assays. The results demonstrated that treatment with ART significantly alleviated the UC symptoms induced by DSS in the rat model, lowered the DAI, ameliorated pathological changes, attenuated colon shortening, inhibited the levels of pro‑inflammatory mediators and myeloperoxidase activity, and increased hemoglobin expression. Additionally, inflammatory and apoptotic markers were found to be significantly downregulated following treatment with ART in UC rats and RAW264.7 cells. To the best of our knowledge, the present study is the first to demonstrate that ART exerts anti‑inflammatory effects via regulating the TLR4‑NF‑κB signaling pathway in UC.
View Figures
View References

Related Articles

Journal Cover

August-2019
Volume 20 Issue 2

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Chen YX, Zhang XQ, Yu CG, Huang SL, Xie Y, Dou XT, Liu WJ and Zou XP: Artesunate exerts protective effects against ulcerative colitis via suppressing Toll‑like receptor 4 and its downstream nuclear factor‑κB signaling pathways. Mol Med Rep 20: 1321-1332, 2019.
APA
Chen, Y., Zhang, X., Yu, C., Huang, S., Xie, Y., Dou, X. ... Zou, X. (2019). Artesunate exerts protective effects against ulcerative colitis via suppressing Toll‑like receptor 4 and its downstream nuclear factor‑κB signaling pathways. Molecular Medicine Reports, 20, 1321-1332. https://doi.org/10.3892/mmr.2019.10345
MLA
Chen, Y., Zhang, X., Yu, C., Huang, S., Xie, Y., Dou, X., Liu, W., Zou, X."Artesunate exerts protective effects against ulcerative colitis via suppressing Toll‑like receptor 4 and its downstream nuclear factor‑κB signaling pathways". Molecular Medicine Reports 20.2 (2019): 1321-1332.
Chicago
Chen, Y., Zhang, X., Yu, C., Huang, S., Xie, Y., Dou, X., Liu, W., Zou, X."Artesunate exerts protective effects against ulcerative colitis via suppressing Toll‑like receptor 4 and its downstream nuclear factor‑κB signaling pathways". Molecular Medicine Reports 20, no. 2 (2019): 1321-1332. https://doi.org/10.3892/mmr.2019.10345