Risk assessment of 2β,3β-19α-trihydroxyursolic acid from Rubus imperialis (Rosaceae) in HepG2/C3A cells via genotoxicity, metabolism, and cell growth

J Appl Toxicol. 2024 Dec;44(12):1886-1896. doi: 10.1002/jat.4684. Epub 2024 Aug 11.

Abstract

Rubus imperialis (Rosaceae) is a Brazilian medicinal plant that already exhibited therapeutical perspectives. However, previous studies revealed cellular and/or genetic toxicity of extracts from aerial parts of this plant, as well as other species of the Rubus genus. Being 2β,3β-19α-trihydroxyursolic acid (2B) one of the major compounds of this plant, with proven pharmacological effect, it is important to investigate the biosafety of this isolated compound. Therefore, in the present study, (2B) was tested by several cytogenotoxic endpoints up to 20 μg/ml in human hepatoma HepG2/C3A cells. The test compound did not produce any decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT-qPCR analysis revealed the downregulation of CYP3A4 (metabolism), M-TOR (cell death), and CDKN1A (cell cycle) genes. Under the experimental conditions used, the 2B compound did not show cytogenotoxic activity after a single exposure to HepG2/C3A human cells.

Keywords: 2β,3β‐19α‐trihydroxyursolic acid toxicity; apoptosis analysis; cell cycle analysis; comet assay; gene expression; micronucleus test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Proliferation* / drug effects
  • Cell Survival* / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism
  • DNA Damage* / drug effects
  • Hep G2 Cells
  • Humans
  • Plant Extracts / pharmacology
  • Plant Extracts / toxicity
  • Risk Assessment
  • Rubus* / chemistry
  • Triterpenes / pharmacology
  • Triterpenes / toxicity

Substances

  • Cytochrome P-450 CYP3A
  • Triterpenes
  • Plant Extracts
  • CYP3A4 protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • CDKN1A protein, human