Toxicological and chemoprevention studies of Dalbergia ecastaphyllum (L.) Taub. stem, the botanical source of Brazilian red propolis

Author:

da Silva Lucas Henrique Domingos1ORCID,Squarisi Iara Silva1,de Freitas Karoline Soares1,Barcelos Ribeiro Arthur1,Ozelin Saulo Duarte1ORCID,Aldana-Mejía Jennyfer Andrea2,de Oliveira Lucas Teixeira Souza1,Rodrigues Tábata Esperandim1,de Melo Matheus Reis Santos1,Nicolella Heloiza Diniz1,Alves Bianca Silva1,de Andrade Melo Alex Luiz1,Ccana-Ccapatinta Gari Vidal2,Bastos Jairo Kenupp2,Tavares Denise Crispim1ORCID

Affiliation:

1. Postgraduate Program in Science, University of Franca, Franca, São Paulo, Brazil

2. School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil

Abstract

Abstract Objectives Dalbergia ecastaphyllum (L.) Taub. is a semi-prostrate species associated with estuaries, mangroves and dunes. This plant species has great ecological and economic importance, especially concerning apiculture pasture and Brazilian red propolis production. In this study, non-clinical toxicological evaluations of the hydroalcoholic extract of D. ecastaphyllum stems (DEHE), the resin production source, were conducted. In addition, the action of DEHE on genomic instability and colon carcinogenesis was investigated. Methods and results The extract’s chemical profile was analysed by HPLC, and medicarpin, vestitol and neovestitol were found as major compounds. DEHE showed an IC50 equivalent to 373.2 µg/ml and LC50 equal 24.4 mg/L, when evaluated using the XTT colorimetric test and the zebrafish acute toxicity assay, respectively. DEHE was neither genotoxic nor cytotoxic at the highest dose, 2000 mg/kg, by peripheral blood micronucleus test. The treatments DEHE (6 and 24 mg/kg) led to the reduction of micronuclei induced by doxorubicin (DXR) in mice. Furthermore, significantly higher serum levels of reduced glutathione were observed in animals treated with DEHE plus DXR, revealing an antioxidant effect. Treatments with DEHE (48 mg/kg) led to a significant reduction in pre-neoplastic lesions induced by the 1,2-dimethylhydrazine (DMH) carcinogen in the rat colon. Immunohistochemical analysis revealed significantly lower levels of expression of COX-2 (86%) and PCNA (83%) in the colon of rats treated with DEHE plus DMH, concerning those treated with the carcinogen. Conclusions These results indicate the involvement of anti-inflammatory and antiproliferative pathways in the protective effect of DEHE.

Funder

São Paulo Research Foundation

FAPESP

Coordination for the Improvement of Higher Education Personnel

CAPES

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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