Estrogenic and chemopreventive activities of xanthones and flavones of Syngonanthus (Eriocaulaceae)

Abstract

The possible benefits of some bioactive flavones and xanthones present in plants of the genus Syngonanthus prompted us to screen them for estrogenic activity. However, scientific research has shown that such substances may have undesirable properties, such as mutagenicity, carcinogenicity and toxicity, which restrict their use as therapeutic agents. Hence, the aim of this study was to assess the estrogenicity and mutagenic and antimutagenic properties. We used recombinant yeast assay (RYA), with the strain BY4741 of Saccharomyces cerevisiae, and Ames test, with strains TA100, TA98, TA97a and TA102 of Salmonella typhimirium, to evaluate estrogenicity, mutagenicity and antimutagenicity of methanolic extracts of Syngonanthus dealbatus (S.d.), Syngonanthus macrolepsis (S.m.), Syngonanthus nitens (S.n.) and Syngonanthus suberosus (S.s.), and of 9 compounds isolated from them (1=luteolin, 2=mix of A-1,3,6-trihydroxy-2-methoxyxanthone and B-1,3,6-trihydroxy-2,5-dimethoxyxanthone, 3=1,5,7-trihydroxy-3,6-dimethoxyxanthone, 4=1,3,6,8-tetrahydroxy-2,5-dimethoxyxanthone, 5=1,3,6,8-tetrahydroxy-5-methoxyxanthone, 6=7-methoxyluteolin-8-C-β-glucopyranoside, 7=7-methoxyluteolin-6-C-β-glucopyranoside, 8=7,3'-dimethoxyluteolin-6-C-β-glucopyranoside and 9=6-hydroxyluteolin). The results indicated the estrogenic potential of the S. nitens methanol extract and four of its isolated xanthones, which exhibited, respectively, 14.74±1.63 nM; 19.54±6.61; 7.20±0.37; 6.71±1.02 e 10.01±4.26 nM of estradiol-equivalents (EEQ). None of the extracts or isolated compounds showed mutagenicity in any of the test strains and all of them showed antimutagenic potential, in particular preventing mutations caused by aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P). The results show that the xanthones, only isolated from the methanol extract of S. nitens capitula, probably were the responsible for its estrogenic activity and could be useful as phytoestrogens, providing a new opportunity to develop hormonal agents. In addition, flavones and xanthones could also be used as a new antimutagenic agent. Since, the mutagens are involved in the initiation and promotion of several human diseases, including cancer, the significance of novel bioactive phytocompounds in counteracting these pro-mutagenic and carcinogenic effects is now gaining credence.

Keywords: +S9; 1; 1,3,6,8-tetrahydroxy-2,5-dimethoxyxanthone; 1,3,6,8-tetrahydroxy-5-methoxyxanthone; 1,5,7-trihydroxy-3,6-dimethoxyxanthone; 17β-estradiol; 2; 3; 4; 4-nitro-O-phenylenediamine, B[a]P, benzo[a]pyrene; 5; 6; 6-hydroxyluteolin; 7; 7,3′-dimethoxyluteolin-6-C-β-glucopyranoside; 7-methoxyluteolin-6-C-β-glucopyranoside; 7-methoxyluteolin-8-C-β-glucopyranoside; 8; 9; AFB(1); Antimutagenicity; BAW; CNPq; Conselho Nacional de Desenvolvimento Científico e Tecnológico; DES; DMSO; E(2); EEQ; ER; ER-RBA; Eriocaulaceae; Estrogenicity; Ex-DCM; Ex-Hex; Ex-MeOH; FAPESP; Fundação de Amparo à Pesquisa do Estado de São Paulo; HRT; HSCCC; I%; MI; Mutagenicity; NPD; Phytoestrogens; RYA; SA; SD; SERMs; Sd; Sm; Sn; Ss; Standard Deviation; UV; aflatoxin B(1); dimethylsulfoxide; estradiol equivalent; estrogen diethylstilbestrol; estrogen receptor; estrogen receptor relative binding affinity; hexane extract; high speed counter current chromatography; hormone replacement therapy; luteolin; methanol extract; methanolic extract of capitula of Syngonanthus dealbatus; methanolic extract of capitula of Syngonanthus macrolepsis; methanolic extract of capitula of Syngonanthus nitens; methanolic extract of capitula of Syngonanthus suberosus; methylene chloride extract; mix of A-1,3,6-trihydroxy-2-methoxyxanthone and B-1,3,6-trihydroxy-2,5-dimethoxyxanthone; mutagenic index; n-butanol, acetic acid and water solution; percent of inhibition of reversion in bacterial strains; recombinant yeast assay; selective estrogen receptor modulators; sodium azide, 2-AA, 2-anthramine, MMC, mitomycin C; ultraviolet light; with metabolization; without metabolization; −S9.