St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling

Soumen K Manna1, Srujana Golla1, Jaya Prakash Golla1

  • 1Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.

Insights

St. John's wort extract shows promise in preventing colorectal cancer. Supplementing mice diets with SJW reduced tumor development and improved survival rates by calming inflammatory pathways.

Area of Science:

  • Pharmacology
  • Gastroenterology
  • Oncology

Background:

  • Colorectal cancer (CRC) remains a significant health concern with limited preventative options.
  • St. John's wort (SJW), a popular herbal remedy, has demonstrated anti-inflammatory properties but its role in CRC prevention is unexplored.
  • Azoxymethane (AOM) is a widely used chemical inducer for modeling CRC in preclinical studies.

Purpose of the Study:

  • To investigate the chemopreventive effects of dietary St. John's wort (SJW) extract on azoxymethane-induced colorectal carcinogenesis in a mouse model.
  • To evaluate the impact of SJW supplementation on survival, tumor development, and key molecular pathways involved in CRC.

Main Methods:

  • Mice were fed either a control diet or a diet supplemented with SJW extract before and during azoxymethane treatment.
  • Tumor multiplicity, incidence, volume, and host physiological parameters were assessed.
  • Expression and activity of Nuclear Factor kappa B (NF-κB) and Extracellular Signal-Regulated Kinase (ERK1/2) pathways were analyzed in colon tissues.

Main Results:

  • SJW supplementation significantly improved survival and mitigated adverse physiological effects (weight loss, hypoalbuminemia, hypocholesterolemia) in AOM-treated mice.
  • A dose-dependent reduction in tumor multiplicity, incidence of large tumors, and total tumor volume was observed in SJW-fed mice.
  • SJW administration led to early and sustained attenuation of NF-κB and ERK1/2 signaling pathways in the colon epithelium.

Conclusions:

  • Dietary SJW extract exhibits significant chemopreventive potential against colorectal cancer.
  • SJW exerts its protective effects by attenuating pro-inflammatory signaling pathways, specifically NF-κB and ERK1/2.
  • These findings support further investigation of SJW as a natural agent for colorectal cancer prevention.

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