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

Author:

Oshiiwa Bruna1,da Silva Aline Pereira2,Alves Greice Rafaele3,Filho Valdir Cechinel3,Niero Rivaldo3,O'Neill de Mascarenhas Gaivão Isabel4,de Oliveira Liana Martins5,de Lima Luan Vitor Alves5,Mantovani Mário Sérgio5ORCID,Maistro Edson Luis12

Affiliation:

1. Faculty of Philosophy and Sciences, Speech and Hearing Therapy Department São Paulo State University (UNESP) Marília São Paulo State Brazil

2. Postgraduate Program in Health and Aging Marilia Medical School (FAMEMA) Marilia São Paulo State Brazil

3. Programa de Pós‐Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico‐Farmacêuticas (NIQFAR) Vale do Itajaí University (UNIVALI) Itajaí Santa Catarina State Brazil

4. CECAV and Department of Genetics and Biotechnology University of Trás‐os‐Montes and Alto Douro Vila Real Portugal

5. Department of General Biology Londrina State University (UEL) Londrina Paraná State Brazil

Abstract

AbstractRubus 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.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Fundação de Amparo à Pesquisa do Estado de São Paulo

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Wiley

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