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Mechanism study of goldenseal-associated DNA damage

Journal Article · · Toxicology Letters
 [1];  [2];  [3];  [3];  [3];  [3];  [3];  [3]
  1. U.S. Food and Drug Administration (FDA), Jefferson, AR (United States). National Center for Toxicological Research; OSTI
  2. U.S. Food and Drug Administration (FDA), Jefferson, AR (United States). National Center for Toxicological Research; Shanghai Institute for Food and Drug Control (China)
  3. U.S. Food and Drug Administration (FDA), Jefferson, AR (United States). National Center for Toxicological Research
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Goldenseal has been used for the treatment of a wide variety of ailments including gastrointestinal disturbances, urinary tract disorders, and inflammation. The five major alkaloid constituents in goldenseal are berberine, palmatine, hydrastine, hydrastinine, and canadine. When goldenseal was evaluated by the National Toxicology Program (NTP) in the standard 2-year bioassay, goldenseal induced an increase in liver tumors in rats and mice; however, the mechanism of goldensealassociated liver carcinogenicity remains unknown. In this study, the toxicity of the five goldenseal alkaloid constituents was characterized, and their toxic potencies were compared. As measured by the Comet assay and the expression of γ-H2A.X, berberine, followed by palmatine, appeared to be the most potent DNA damage inducer in human hepatoma HepG2 cells. Berberine and palmatine suppressed the activities of both topoisomerase (Topo) I and II. In berberine-treated cells, DNA damage was shown to be directly associated with the inhibitory effect of Topo II, but not Topo I by silencing gene of Topo I or Topo II. In addition, DNA damage was also observed when cells were treated with commercially available goldenseal extracts and the extent of DNA damage was positively correlated to the berberine content. Our findings suggest that the Topo II inhibitory effect may contribute to berberine- and goldenseal-induced genotoxicity and tumorigenicity.

Research Organization:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC); U.S. Food and Drug Administration (FDA)
Grant/Contract Number:
SC0014664
OSTI ID:
1905029
Journal Information:
Toxicology Letters, Journal Name: Toxicology Letters Journal Issue: 1 Vol. 221; ISSN 0378-4274
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Berberine
Comet assay
DNA damage
Gamma-H2A.X
Goldenseal
Topoisomerase
Toxicology