Molekularne mechanizmy działania genisteiny w świetle terapii chorób genetycznych i immunologicznych

Węgrzyn, Grzegorz; Pierzynowska, Karolina; Podlacha, Magdalena; Brokowska, Joanna; Gaffke, Lidia; Mantej, Jagoda; Cyske, Zuzanna; Rintz, Estera; Osiadły, Marta; Bartkowski, Michał; Puchalski, Michał; Grabski, Michał; Pierzynowski, Michał; Bedran, Dominika; Piotrowska, Ewa; Tukaj, Stefan

doi:10.18388/pb.2018_140

Cited by 5 publications

(3 citation statements)

References 94 publications

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“…Lee et al [ 44 ] showed that genistein supplementation of diethylnitrosamine (DEN)-treated mice results in decreased IL-6 and TNF gene expression (relative to control animals). The anti-inflammatory effects of genistein have been demonstrated in a number of studies [ 45 ]. Interestingly, it was found that animals supplemented with nano-, micro-, and macrogenistein had higher levels of metalloproteinase-9, MMP-9, compared to animals without supplementation.…”

Section: Discussionmentioning

confidence: 99%

Inflammation Factors and Genistein Supplementation in Cancer—Preliminary Research

Banyś,

Jelińska,

Wrzosek

et al. 2024

CIMB

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The purpose of this study was to evaluate the effect of genistein in nano, micro, and macro forms on the intensity of the DMBA-induced tumor process in rats and to understand the mechanisms of this action. The effect of genistein supplementation on the content of selected eicosanoids (HETEs, HODE, and HEPE) in the serum of rats was evaluated. The levels and expression of genes encoding various pro-inflammatory cytokines (IL-1, IL-6) and MMP-9 in the blood of rats were also investigated. The biological material for the study was blood obtained from female rats of the Sprague Dawley strain (n = 32). The animals were randomly divided into four groups: animals without supplementation, and animals supplemented at a dose of 0.2 mg/kg b.w. (0.1 mg/mL) with macro, micro (587 ± 83 nm), or nano (92 ± 41 nm) genistein. To induce mammary neoplasia (adenocarcinoma), rats were given 7,12-dimethyl-1,2-benz[a]anthracene (DMBA). The content of selected eicosanoids was determined by liquid chromatography with UV detection. An immunoenzymatic method was used to determine the content of cytokines and MMP-9. The expression of the IL-6, IL-1beta, and MMP-9 genes was determined with quantitative real-time PCR (qRT-PCR) using TaqMan probes. Based on the study, it was shown that supplementation of animals with genistein in macro, micro, and nano forms increased the intensity of the tumor process in rats. It was shown that the content of 12-HEPE, HODE, and 12-HETE in the serum of genistein-supplemented rats was statistically significantly lower with respect to the content of the aforementioned markers in the serum of rats receiving only a standard diet, devoid of supplementation. It was found that animals supplemented with nano-, micro-, and macrogenistein had higher levels of metalloproteinase-9, MMP-9, compared to animals without supplementation. There was a significant increase in MMP-9 gene expression in the blood of macrogenistein-supplemented animals, relative to the other groups of rats. On the basis of the study, it was shown that supplementation of animals with nano-, micro-, and macrogenistein had an effect on the development of the tumor process. Dietary supplementation with genistein significantly decreased the level of selected eicosanoids, which may have significant impacts on cancer development and progression.

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Section: Discussionmentioning

confidence: 99%

Inflammation Factors and Genistein Supplementation in Cancer—Preliminary Research

Banyś,

Jelińska,

Wrzosek

et al. 2024

CIMB

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“…It occurs in nature in both free (as an aglycone) and glycosidic form (as a genistin). Due to its pleiotropic action, genistein exhibits a broad spectrum of biological effects that contribute to its potentially beneficial effects on health [4][5]. Its primary function in the human body encompasses estrogenic, antioxidant and anti-inflammatory activity.…”

Section: Introductionmentioning

confidence: 99%

“…These include conditions related to old age, such as cancer, Alzheimer's disease, osteoporosis and inflammatory diseases [4]. In addition, genistein is reported to show positive effects in patients with type II diabetes, kidney diseases, cardiovascular diseases or genetic dysfunctions (Sanfilippo syndrome, Huntington's disease, cystic fibrosis, amyotrophic lateral sclerosis) [4][5].…”

Section: Introductionmentioning

confidence: 99%

Molecular Insights into Genistein-NSAID Hybrids – Synthesis, Characterisation and DFT Study

Kossakowski,

Żwawiak,

Cherniienko

et al. 2024

Preprint

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Genistein (GEN) is one of the pharmaceutically valuable phenolic compounds, which belongs to the isoflavone group of flavonoids and is a natural phytohormone found mainly in soybeans and red clover. It affects estrogen receptors, functioning as a selective estrogen receptor modulator (SERM) with anti-inflammatory and antioxidant activity. The presence of reactive phenolic groups in genistein provides an opportunity to expand its structure by introducing components responsible for anti-inflammatory properties. Such an innovative combination of a compound with anticancer and antioxidant potential with an anti-inflammatory compound (NSAID) may lead to interesting new derivatives with dual mechanisms of biological action. The synthesis and characterisation of genistein-NSAID hybrid compounds (ibuprofen, ketoprofen, naproxen, flurbiprofen) was conducted, together with a comprehensive structural and quantum chemistry DFT (Density Functional Theory) computational analysis allowing the description of 1H-NMR and 13C-NMR spectroscopic properties of the starting compounds and the resulting hybrids. The study resulted in the formation of seven hybrid GEN-NSAID derivatives. In the case of ibuprofen, ketoprofen and flurbiprofen, a mixture of isomeric hybrid GEN-4’-NSAID and GEN-7-NSAID derivatives was obtained, whereas, for naproxen, only GEN-4’-NSAID was formed. The structural characteristics of the resulting compounds were determined using MS, IR, 1H-NMR and 13C-NMR spectroscopic methods. The most accurate DFT computational methods for predicting 1H-NMR and 13C-NMR spectra were also established with statistical parameters to assess their accuracy.

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The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

Teixeira

Sousa

Gomes

et al. 2021

Preprint

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BackgroundThe Trypanosoma cruzi infection renders the transfer of the mitochondrion kinetoplast DNA minicircle sequences into the host’s genome. The Aves are refractory to the infection, but chicks hatched from the T. cruzi inoculated eggs integrate the DNA minicircle sequences into the germ line cells. Rabbits, mice and chickens with the minicircle sequences mutations develop the Chagas cardiomyopathy and the DNA transfer underpins the heart disease.MethodologyThe PCR with the specific primer sets revealed the Protist nuclear DNA and the kinetoplast DNA in the agarose gels bands probed with the radiolabel specific sequences from tissues of the T. cruzi-infected rabbits and of the mice. A target- primer TAIL-PCR amplification employing primer sets from the chickens, rabbits and mice, in combination with primer sets from the the T. cruzi kinetoplast minicircle sequences was used. This approach led us to disclose the integration sites of the kinetoplast DNA biomarker, then, used to monitor the effect of multidrug treatment of the T. cruzi infected mice.Principal findingsThe Southern hybridization, clone and sequence of the amplification products revealed the DNA minicircle sequences integrations sites in the LINE transposable elements. An array of inhibitors of eukaryote cells division was used to arrest the DNA transfer. It was shown that nine out of 12 inhibitors prevented the kinetoplast DNA integration into the macrophage genome. The multidrug treatment of the acutely T. cruzi-infected mice with Benznidazole, Azidothymidine and Ofloxacin lessened circa 2.5-fold the rate of the minicircle sequences integrations in the mouse genome and inhibited the rejection of the target heart cells.Conclusion and significanceThe T. cruzi mitochondrion kinetoplast minicircle sequences transfer driven pathogenesis of Chagas disease is an ancient Cross-Kingdom DNA phenomenon of evolution and, therefore, paradigm research with effective purposing inhibitors is needed.Authors summaryChagas disease is considered the main cause of human heart failure in the Western Hemisphere. The treatment of the clinically manifested Chagas heart disease is considered unsatisfactory. Perhaps the most important problem in the field of Chagas disease is determination of the pathogenesis of the target heart cells lysis. We showed the transfer of the T. cruzi kDNA minicircle sequences into the genome of rabbits and mice, and to Bird refractory to the infections. The inoculation of a few T. cruzi in the fertile chicken eggs renders the kDNA sequences integration in the stem cells. Interestingly, the chicks that hatched retain the kDNA and develop the Chagas-like cardiomyopathy indistinguishable to that in the rabbits and mice. This result prompted the multidrug treatment of the Chagas heart disease with inhibitors of the eukaryotic cells division. We showed that nine out of 12 inhibitors prevented the transfer of the kDNA mutations into the macrophage genome, and that the treatment of the acutely T. cruzi-infected mice with Benznidazole + Ofloxacin + Azidothymidine lowered circa 2.5-fold the rate of the mutations in the chromosomes. These findings translated to the pathology showing inhibition of the heart lesions in the treated T. cruzi-infected mice. We suggest purposing new inhibitors should be tested to overturning the Chagas heart disease.

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Molekularne mechanizmy działania genisteiny w świetle terapii chorób genetycznych i immunologicznych

Cited by 5 publications

References 94 publications

Inflammation Factors and Genistein Supplementation in Cancer—Preliminary Research

Inflammation Factors and Genistein Supplementation in Cancer—Preliminary Research

Molecular Insights into Genistein-NSAID Hybrids – Synthesis, Characterisation and DFT Study

The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

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