Analysis of the effects of manool, a diterpene of Salvia officinalis, on cell and genomic integrity.

• Grant number: 16/24269-7
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2017
• End date: June 30, 2019
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Denise Crispim Tavares Barbosa
• Grantee: Denise Crispim Tavares Barbosa
• Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil

Abstract

The Salvia genus is the largest in the Lamiaceae family, with more than 900 species, and Salvia officinalis is a species that has many therapeutic activities, such as anti-inflammatory, antimicrobial, eupeptic and anti-depressive. In addition, it is used in cooking as a condiment. In extracts of S. officinalis, terpenoids and phenolic compounds were identified as the main classes of special metabolites, with diterpenes being their most characteristic micrometabolites. Among these, manool stands out in the scientific literature as one of the most abundant components of essential oils and extracts of S. officinalis. Previous studies performed by our research group have shown the genotoxic effect of manool on cultures of V79 (Chinese hamster lung fibroblasts) and HepG2 (human hepatocarcinoma) cells. On the other hand, smaller non-genotoxic concentrations of this diterpene were able to reduce the genotoxicity of the methyl methanesulfonate mutagen in HepG2 cells, but not in V79 cells. Additionally, manool showed cytotoxic effect in different tumor cell lines, exhibiting significant selectivity. The present study aims to broaden the genotoxic evaluation necessary for drug candidates for human use through in vivo toxicogenic study and dosage of liver enzymes as a parameter of liver toxicity. In addition, different analyzes will be conducted aiming at a better understanding of the action of manool as its influence on the cell cycle and the cell death pathways, by flow cytometry; its effect on genotoxicity induced by mutagens with different mechanisms of action, such as doxorubicin, hydrogen peroxide and etoposide, using the micronucleus test; and the analysis of the expression of genes related to anti-inflammatory pathways (NF-ºB, nuclear factor kappa B), antioxidant (Nrf-2, nuclear factor erythroid 2 [NF-E2] -related factor 2, factor 2) and pro-apoptotic nuclear (TP53, tumor suppressor gene) by Western blot, as possible mechanisms involved in its action. The results obtained from the different biological evaluations will allow a better understanding of the action of manool on the organism, contributing to the safe and effective use in future therapeutic applications. (AU)

Scientific publications

(11)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CRUZ, ROBERTA CRISTINA RIBEIRO; NETO, FRANCISCO RINALDI; FURTADO, RICARDO ANDRADE; SOUZA, LARISSA MENDES; DE SOUSA, FERNANDA DINIZ; OZELIN, SAULO DUARTE; BASTOS, JAIRO KENUPP; MAGALHAES, GEORGIA MODE; TAVARES, DENISE CRISPIM; DE OLIVEIRA, POLLYANNA FRANCIELLI. Watermelon Reduces the Toxicity of Cisplatin Treatment in C57BL/6 Mice with Induced Melanoma. NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, APR 2021. (16/24269-7)

GONCALVES DIAS, FERNANDA GOSUEN; PEREIRA, LUCAS DE FREITAS; TAME PARREIRA, RENATO LUIS; SOLA VENEZIANI, RODRIGO CASSIO; BIANCHI, THAMIRES CHIQUINI; NOGUEIRA DE PAULA FONTES, VITORIA FERREIRA; GALVANI, MARINA DE CARLOS; CERCE, DANIELLE DAL PICOLO; GOMES MARTINS, CARLOS HENRIQUE; RINALDI-NETO, FRANCISCO; et al. Evaluation of the antiseptic and wound healing potential of polyhexamethylene guanidine hydrochloride as well as its toxic effects. European Journal of Pharmaceutical Sciences, v. 160, MAY 1 2021. (16/24269-7)

NICOLELLA, HELOIZA D. D.; RIBEIRO, ARTHUR B. B.; MUNARI, CARLA CAROLINA; MELO, MATHEUS R. R.; OZELIN, SAULO D. D.; DA SILVA, LUCAS HENRIQUE D.; MARQUELE-OLIVEIRA, FRANCIANE; ORENHA, RENATO P. P.; VENEZIANI, RODRIGO CASSIO S.; PARREIRA, RENATO LUIS T.; et al. Antimelanoma effect of manool in 2D cell cultures and reconstructed human skin models. JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, v. N/A, p. 12-pg., 2022-12-21. (16/24269-7)

CARABAJAL, MONICA PATRICIA ANTONELLA; PILOTO-FERRER, JANET; NICOLLELA, HELOIZA DINIZ; SQUARISI, IARA SILVA; GUISSONE, ANA PAULA PRADO; ESPERANDIM, TABATA RODRIGUES; TAVARES, DENISE CRISPIM; ISLA, MARIA INES; ZAMPINI, IRIS CATIANA. Antigenotoxic, antiproliferative and antimetastatic properties of a combination of native medicinal plants from Argentina. Journal of Ethnopharmacology, v. 267, MAR 1 2021. (16/24269-7)

RIBEIRO, ARTHUR B.; OZELIN, SAULO D.; DA SILVA, LUCAS H. D.; RINALDI-NETO, FRANCISCO; FREITAS, KAROLINE S.; NICOLELLA, HELOIZA D.; DE SOUZA, LARISSA D. R.; FURTADO, RICARDO A.; CUNHA, WILSON ROBERTO; TAVARES, DENISE C.. Influence of Asiatic acid on cell proliferation and DNA damage in vitro and in vivo systems. JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, v. 35, n. 4, JAN 2021. (16/24269-7, 16/21068-0)

CRUZ, ROBERTA CRISTINA RIBEIRO; NETO, FRANCISCO RINALDI; FURTADO, RICARDO ANDRADE; SOUZA, LARISSA MENDES; DE SOUSA, FERNANDA DINIZ; OZELIN, SAULO DUARTE; BASTOS, JAIRO KENUPP; MAGALHAES, GEORGIA MODE; TAVARES, DENISE CRISPIM; DE OLIVEIRA, POLLYANNA FRANCIELLI. Watermelon Reduces the Toxicity of Cisplatin Treatment in C57BL/6 Mice with Induced Melanoma. NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, v. 74, n. 3, p. 9-pg., 2021-04-20. (16/24269-7)

RINALDI-NETO, FRANCISCO; RIBEIRO, ARTHUR BARCELOS; FERREIRA, NATALIA HELEN; SQUARISI, IARA SILVA; OLIVEIRA, KATIA MARA; ORENHA, RENATO PEREIRA; TAME PARREIRA, RENATO LUIS; BATISTA, ALZIR AZEVEDO; TAVARES, DENISE CRISPIM. nti-melanoma effect of ruthenium(II)-diphosphine complexes containing naphthoquinone ligan. Journal of Inorganic Biochemistry, v. 222, SEP 2021. (16/24269-7, 18/19342-2)

ANDRADE, GABRIELA CARVALHO; PEREIRA BRANCINI, GUILHERME THOMAZ; ABE, FLAVIA RENATA; DE OLIVEIRA, DANIELLE PALMA; NICOLELLA, HELOIZA DINIZ; TAVARES, DENISE CRISPIM; DITONDO MICAS, ANDRE FERNANDO; SAVAZZI, EDUARDO ANGELINO; SILVA-JUNIOR, GERALDO JOSE; WAINWRIGHT, MARK; et al. henothiazinium dyes for photodynamic treatment present lower environmental risk compared to a formulation of trifloxystrobin and tebuconazol. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 226, JAN 2022. (16/24269-7, 18/24298-2, 18/06945-0, 16/11386-5, 14/50945-4)

FERREIRA, NATALIA HELEN; RIBEIRO, ARTHUR BARCELOS; RINALDI-NETO, FRANCISCO; FERNANDES, FERNANDA SANTOS; DO NASCIMENTO, SAMUEL; BRAZ, WILSON RODRIGUES; NASSAR, EDUARDO JOSE; TAVARES, DENISE CRISPIM. Anti-Melanoma Activity of Indomethacin Incorporated into Mesoporous Silica Nanoparticles. PHARMACEUTICAL RESEARCH, v. 37, n. 9, AUG 23 2020. (16/24269-7)

NICOLELLA, HELOIZA DINIZ; RIBEIRO, ARTHUR BARCELOS; SANTOS DE MELO, MATHEUS REIS; OZELIN, SAULO DUARTE; DOMINGOS DA SILVA, LUCAS HENRIQUE; SOLA VENEZIANI, RODRIGO CASSIO; TAVARES, DENISE CRISPIM. Antitumor Effect of Manool in a Murine Melanoma Model. Journal of Natural Products, v. 85, n. 2, p. 7-pg., 2022-02-25. (16/24269-7)

NICOLELLA, HELOIZA DINIZ; FERNANDES, GABRIELA; OZELIN, SAULO DUARTE; RINALDI-NETO, FRANCISCO; RIBEIRO, ARTHUR BARCELOS; FURTADO, RICARDO ANDRADE; SENEDESE, JULIANA MARQUES; ESPERANDIM, TABATA RODRIGUES; SOLA VENEZIANI, RODRIGO CASSIO; TAVARES, DENISE CRISPIM. anool, a diterpene from Salvia officinalis, exerts preventive effects on chromosomal damage and preneoplastic lesion. MUTAGENESIS, v. 36, n. 2, p. 177-185, MAR 2021. (16/24269-7)