title: 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.
authors.affiliation: Department of Biological Sciences, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University, UNESP, Rodovia Araraquara-Jaú Km 1, 14801-902 Araraquara, SP, Brazil.
authors.forename: Ana Paula Siqueira
authors.initials: AP
authors.lastname: de Oliveira
authors.forename: Juliana Ferreira
authors.initials: JF
authors.lastname: de Sousa
authors.forename: Marcelo Aparecido
authors.initials: MA
authors.lastname: da Silva
authors.forename: Felipe
authors.initials: F
authors.lastname: Hilário
authors.forename: Flávia Aparecida
authors.initials: FA
authors.lastname: Resende
authors.forename: Mariana Santoro
authors.initials: MS
authors.lastname: de Camargo
authors.forename: Wagner
authors.initials: W
authors.lastname: Vilegas
authors.forename: Lourdes Campaner
authors.initials: LC
authors.lastname: dos Santos
authors.forename: Eliana Aparecida
authors.initials: EA
authors.lastname: Varanda
mesh_terms: D016587:Antimutagenic Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D018890:Chemoprevention; D039262:Eriocaulaceae / Q000737:chemistry*; D004967:Estrogens / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D047309:Flavones / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D000432:Methanol / Q000737:chemistry; D009153:Mutagens / Q000633:toxicity; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D012475:Salmonella / Q000187:drug effects; D044004:Xanthones / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D016587:Antimutagenic Agents; D004967:Estrogens; D047309:Flavones; D009153:Mutagens; D010936:Plant Extracts; D044004:Xanthones; C009689:xanthone; D000432:Methanol
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