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

• Published in: Journal of applied toxicology 2024-12, Vol.44 (12), p.1886-1896
• Main Authors: Oshiiwa, Bruna, Silva, Aline Pereira, Alves, Greice Rafaele, Filho, Valdir Cechinel, Niero, Rivaldo, O'Neill de Mascarenhas Gaivão, Isabel, Oliveira, Liana Martins, Lima, Luan Vitor Alves, Mantovani, Mário Sérgio, Maistro, Edson Luis
• Format: Article
• Language: English
• Subjects: 2β,3β‐19α‐trihydroxyursolic acid toxicity; Apoptosis; Apoptosis - drug effects; apoptosis analysis; Biosafety; Cell cycle; Cell Cycle - drug effects; cell cycle analysis; Cell death; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; comet assay; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; DNA damage; DNA Damage - drug effects; gene expression; Genotoxicity; Hep G2 Cells; Hepatoma; Herbal medicine; Humans; Medicinal plants; micronucleus test; Plant extracts; Plant Extracts - pharmacology; Plant Extracts - toxicity; Risk Assessment; Rosaceae; Rubus; Rubus - chemistry; Triterpenes - pharmacology; Triterpenes - toxicity
• ISSN: 0260-437X; 1099-1263; 1099-1263
• DOI: 10.1002/jat.4684

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. Rubus imperialis (Rosaceae) is a medicinal plant. However, it revealed cellular/genetic toxicity. Being 2β,3β‐19α‐trihydroxyursolic acid (2B) is a major compound of this plant, but its biosafety was not investigated. Therefore, (2B) was tested by cytogenotoxic endpoints in HepG2/C3A cells. The compound did not produce any of decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT‐qPCR analysis revealed downregulation of CYP3A4 (metabolism), M‐TOR (cell death), and CDKN1A (cell cycle) genes.