Hedyotis diffusa Suppresses Colitis-Associated Colorectal Cancer via Inhibition of the IL-17A-IL-17RA Axis and NF-κB

Yun-Jhu Hou1, Chien-Yun Hsiang2, Hsin-Yi Lo3

  • 1Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 106319, Taiwan.

Insights

Hedyotis diffusa extract and ferulic acid combat inflammation-driven colorectal cancer by suppressing key immune signals like interleukin-17A and NF-κB, reducing tumor growth and improving survival.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Chronic inflammation drives colorectal cancer (CRC) via interleukin-17A (IL-17A) and nuclear factor-κB (NF-κB) signaling.
  • These pathways promote immune cell infiltration and tumor progression in CRC.

Purpose of the Study:

  • To investigate the anti-tumor effects and molecular mechanisms of Hedyotis diffusa (HD) extract and ferulic acid (FA).
  • To evaluate their efficacy in a colitis-associated CRC mouse model.

Main Methods:

  • Utilized an azoxymethane/dextran sulfate sodium (AOM/DSS) induced colitis-associated CRC mouse model.
  • Administered standardized HD extract and ferulic acid.
  • Performed transcriptomic analysis and molecular docking.
  • Assessed tumor burden, survival, histopathology, immune cell infiltration, IL-17A production, and NF-κB activation.

Main Results:

  • HD and FA treatments significantly alleviated colitis, reduced tumor number/size, improved survival, and decreased tissue damage.
  • Transcriptomic analysis showed suppression of IL-17A and NF-κB signaling pathways.
  • Molecular docking suggested FA binds IL-17A, potentially disrupting IL-17A/IL-17RA interaction.
  • HD and FA reduced immune cell infiltration, IL-17A levels, and NF-κB activation in colonic tissues.

Conclusions:

  • Hedyotis diffusa extract and ferulic acid demonstrate significant anti-tumor efficacy against inflammation-associated CRC.
  • HD targets the IL-17A/IL-17RA axis and downstream NF-κB signaling for protective effects.
  • These findings provide mechanistic insights into IL-17A-centered immunomodulation in colorectal tumorigenesis.

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