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Abstract Title:

Manool, a diterpene from Salvia officinalis, exerts preventive effects on chromosomal damage and pre-neoplastic lesions.

Abstract Source:

Mutagenesis. 2021 Jan 29. Epub 2021 Jan 29. PMID: 33512444

Abstract Author(s):

Heloiza Diniz Nicolella, Gabriela Fernandes, Saulo Duarte Ozelin, Francisco Rinaldi-Neto, Arthur Barcelos Ribeiro, Ricardo Andrade Furtado, Juliana Marques Senedese, Tábata Rodrigues Esperandim, Rodrigo Cassio Sola Veneziani, Denise Crispim Tavares

Article Affiliation:

Heloiza Diniz Nicolella

Abstract:

The present study aimed to evaluate the effect of the manool diterpene on genomic integrity. For this purpose, we evaluated the influence of manool on genotoxicity induced by mutagens with different mechanisms of action, as well as on colon carcinogenesis. The results showed that manool (0.5 and 1.0µg/mL) significantly reduced the frequency of micronuclei induced by doxorubicin (DXR) and hydrogen peroxide in V79 cells but did not influence genotoxicity induced by etoposide. Mice receiving manool (1.25 mg/kg) exhibited a significant reduction (79.5%) in DXR-induced chromosomal damage. The higher doses of manool (5.0 and 20 mg/kg) did not influence the genotoxicity induced by DXR. The anticarcinogenic effect of manool (0.3125, 1.25 and 5.0 mg/kg) was also observed against pre-neoplastic lesions chemically induced in rat colon. A gradual increase in manool doses did not cause a proportional reduction of pre-neoplastic lesions, thus demonstrating the absence of a dose-response relationship. The analysis of serum biochemical indicators revealed the absence of hepatotoxicity and nephrotoxicity of treatments. To explore the chemopreventive mechanisms of manool via anti-inflammatory pathways, we evaluated its effect on nitric oxide (NO) production and on the expression of the NF-kB gene. At the highest concentration tested (4 μg/mL), manool significantly increased NO production when compared to the negative control. On the other hand, in the prophylactic treatment model, manool(0.5 and 1.0 μg/mL) was able to significantly reduce NO levels produced by macrophages stimulated with lipopolysaccharide. Analysis of NF-kB in hepatic and renal tissues of mice treated with manool and DXR revealed that the mutagen was unable to stimulate expression of the gene. In conclusion, manool possesses antigenotoxic and anticarcinogenic effects and its anti-inflammatory potential might be related, at least in part, to its chemopreventive activity.

Study Type : Animal Study

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