Investigating the potential for toxicity from long-term use of the herbal products, goldenseal and milk thistle

Toxicol Pathol. 2011 Feb;39(2):398-409. doi: 10.1177/0192623310394211. Epub 2011 Feb 7.

Abstract

Two-year toxicity studies were conducted on the widely used herbal products, goldenseal and milk thistle, in male and female F344/N rats and B6C3F1 mice. With goldenseal root powder, the primary finding was an increase in liver tumors in rats and mice, and with milk thistle extract, a decrease in spontaneous background tumors including mammary gland tumors in female rats and liver tumors in male mice. Increased tumorigenicity in rodents exposed to goldenseal root powder may be due in part to the topoisomerase inhibition properties of berberine, a major alkaloid constituent in goldenseal, or its metabolite, berberrubine. In the clinic, use of topoisomerase-inhibiting agents has been associated with secondary tumor formation and inhibition in DNA repair processes. In contrast, the radical-scavenging and antioxidant properties of silibinin and other flavonolignans in milk thistle extract may have contributed to the decrease in background tumors in rodents in the present studies. The fate of the active constituents of goldenseal and milk thistle is similar in humans and rodents; therefore, the modes of action may translate across species. Further studies are needed to extrapolate the findings to humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Berberine / analogs & derivatives
  • Berberine / pharmacokinetics
  • Berberine / toxicity
  • Body Weight
  • Carcinogens / toxicity*
  • Female
  • Flavonolignans / pharmacology
  • Hydrastis / chemistry
  • Hydrastis / toxicity*
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Milk Thistle / chemistry*
  • Plant Preparations / administration & dosage
  • Plant Preparations / chemistry
  • Plant Preparations / toxicity*
  • Plant Roots / chemistry
  • Rats
  • Rats, Inbred F344
  • Silybin
  • Silymarin / pharmacology
  • Topoisomerase Inhibitors / toxicity
  • Toxicity Tests, Chronic

Substances

  • Carcinogens
  • Flavonolignans
  • Plant Preparations
  • Silymarin
  • Topoisomerase Inhibitors
  • Berberine
  • berberrubine
  • Silybin