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Tuesday, 21 April 2015

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

Steroids
Volume 78, Issue 11, November 2013, Pages 1053–1063

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


doi:10.1016/j.steroids.2013.07.002
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Highlights

•
Syngonanthus nitens extract and its isolated xanthones demonstrated estrogenic activity.
•
None of the extracts or isolated compounds showed mutagenic activity.
•
Flavones and xanthones could also be used as a new antimutagenic agent.

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.

Graphical abstract

Estrogenicity assay: Methanol extract of S. nitens (Sn) and xanthones 2, 5, 3 and 4 were significantly different (∗) from negative control (DMSO) (α = 0.05) and were considered estrogenic in the recombinant yeast assay (RYA). Antimutagenicity assay (Ames test): All the isolated compounds displayed more strong antimutagenic activity for TA100, reaching the inhibiting 62% (1); 55% (2); 51% (3); 89% (5); 69% (6); 75% (7); 85% (8) and 75% (9) of the mutagenic effect of aflatoxin B1. 4 showed more significantly results for TA98 and inhibited 54% of the mutagenicity caused by benzo[a]pyrene. ∗Concentrations that were significantly different from positive controls (TA100: Aflatoxin B1; TA98: benzo[a]pyrene) (α = 0.05).
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Abbreviations

  • RYA, recombinant yeast assay;
  • Sd, methanolic extract of capitula of Syngonanthus dealbatus;
  • Sm, methanolic extract of capitula of Syngonanthus macrolepsis;
  • Sn, methanolic extract of capitula of Syngonanthus nitens;
  • Ss, methanolic extract of capitula of Syngonanthus suberosus;
  • 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;
  • 9, 6-hydroxyluteolin;
  • EEQ, estradiol equivalent;
  • SERMs, selective estrogen receptor modulators;
  • ER, estrogen receptor;
  • HRT, hormone replacement therapy;
  • SA, sodium azide, 2-AA, 2-anthramine, MMC, mitomycin C;
  • NPD, 4-nitro-O-phenylenediamine, B[a]P, benzo[a]pyrene;
  • AFB1, aflatoxin B1;
  • Ex-Hex, hexane extract;
  • Ex-DCM, methylene chloride extract;
  • Ex-MeOH, methanol extract;
  • BAW, n-butanol, acetic acid and water solution;
  • UV, ultraviolet light;
  • HSCCC, high speed counter current chromatography;
  • DMSO, dimethylsulfoxide;
  • MI, mutagenic index;
  • +S9, with metabolization;
  • −S9, without metabolization;
  • DES, estrogen diethylstilbestrol;
  • E2, 17β-estradiol;
  • ER-RBA, estrogen receptor relative binding affinity;
  • FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo;
  • CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
  • SD, Standard Deviation;
  • I%, percent of inhibition of reversion in bacterial strains

Keywords

  • Eriocaulaceae;
  • Estrogenicity;
  • Mutagenicity;
  • Antimutagenicity;
  • Phytoestrogens

Corresponding author. Tel.: +55 16 3301 4672; fax: +55 16 3301 6940.
Copyright © 2013 Elsevier Inc. All rights reserved.
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