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  • Author: Przemyslaw M. Mrozikiewicz x
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Open access

Przemyslaw M. Mrozikiewicz, Anna Bogacz, Joanna Bartkowiak-Wieczorek, Radoslaw Kujawski, Przemyslaw L. Mikolajczak, Marcin Ozarowski, Boguslaw Czerny, Beata Mrozikiewicz-Rakowska and Edmund Grzeskowiak

Abstract

There are a number of compounds that can modify the activity of ABC (ATP-binding cassette) and SLC (solute carrier) transporters in the blood-brain barrier (BBB). The aim of this study was to investigate the effect of natural and synthetic substances on the expression level of genes encoding transporters present in the BBB (mdr1a, mdr1b, mrp1, mrp2, oatp1a4, oatp1a5 and oatp1c1). Our results showed that verapamil caused the greatest reduction in the mRNA level while other synthetic (piracetam, phenobarbital) and natural (codeine, cyclosporine A, quercetin) substances showed a selective inhibitory effect. Further, the extract from the roots of Panax ginseng C. A. Meyer exhibited a decrease of transcription against selected transporters whereas the extract from Ginkgo biloba L. leaves resulted in an increase of the expression level of tested genes, except for mrp2. Extract from the aerial parts of Hypericum perforatum L. was the only one to cause an increased mRNA level for mdr1 and oatp1c1. These findings suggest that herbs can play an important role in overcoming the BBB and multidrug resistance to pharmacotherapy of brain cancer and mental disorders, based on the activity of selected drug-metabolizing enzymes and transporters located in the BBB

Open access

Radosław Kujawski, Joanna Bartkowiak-Wieczorek, Anna Bogacz, Monika Karasiewicz, Przemysław Ł. Mikołajczak, Bogusław Czerny and Przemysław M. Mrozikiewicz

Abstract

The aim of this study was to investigate the influence of standardized crude aqueous Epilobium angustifolium L. extract [100 mg/kg/day, p.o.] on the expression level of SRC kinase mRNA - a representatives of non-genomics xenobiotics signaling pathway in prostate ventral lobes of testosterone-induced, castrated rats. We have shown that in all analyzed groups induced by testosterone an elevation of SRC kinase mRNA transcription was observed, in comparison to control animals (not receiving the testosterone), (p<0.05). Finasteride in rats induced by testosterone caused the strongest inhibition of SRC mRNA transcription (p<0.05). In rats receiving testosterone and the plant extract a ca. 90% decrease of mRNA level was observed vs. testosterone-induced animals (p<0.05), while in testosterone-induced animals receiving concomitantly E. angustifolium extract and finasteride the observed reduction reached 87.3% (p<0.05).

We did not observed, however, any positive feedback between studied plant extract and finasteride in the inhibitory activity (p<0.05). Further experimental studies should be performed in order to the understanding the molecular basis of interactions, the efficacy and safety of tested plant extract.

Open access

Radosław Kujawski, Joanna Bartkowiak-Wieczorek, Monika Karasiewicz, Anna Bogacz, Przemysław Ł. Mikołajczak, Bogusław Czerny and Przemysław M. Mrozikiewicz

Abstract

The aim of this study was to investigate the influence of standardized Epilobium angustifolium L. extract [100 mg/kg/day, p.o.] on the expression level of 5α-reductase type 2 (Srd5ar2) mRNA and Mapk3 mRNA a representative of non-genomic xenobiotics signaling pathway. It was shown that plant extract from the E. angustifolium showed a slight tendency to reduce prostate weight in hormonally induced animals (p>0.05) and in testosterone induced animals receiving both, extract and finasteride (p<0.05). Finasteride in rats induced by testosterone caused a smaller decrease in the level of mRNA 5α-steroid reductase 2 (SRd5ar2), than in rats treated with the hormone and studied plant extracts. In general, an increase in the amount of MAPK3 mRNAs in testosterone-induced groups of rats receiving tested plant extract with or without finasteride was observed, while the expression of type 2 5α-steroid reductase decreased (p<0.05). Further experimental studies should be performed in order to understand the molecular basis of interactions, the efficacy and safety of tested plant extracts.

Open access

Anna Bogacz, Monika Karasiewicz, Joanna Bartkowiak-Wieczorek, Marcin Ożarowski, Agnieszka Seremak-Mrozikiewicz, Radosław Kujawski, Przemysław Ł. Mikołajczak, Beata Mrozikiewicz-Rakowska, Teresa Bobkiewicz-Kozłowska, Bogusław Czerny, Edmund Grześkowiak and Przemysław M. Mrozikiewicz

Abstract

Green tea (Camellia sinensis) is widely used as a popular beverage and dietary supplement that can significantly reduce the risk of many diseases. Despite the widespread use of green tea, the data regarding the safety as well as herb-drug interactions are limited. Therefore, the aim of our study was to assess the influence of standardized green tea extract (GTE) containing 61% catechins and 0.1% caffeine on the expression level of rat CYP genes and the corresponding transcription factors expression by realtime PCR. The findings showed that GTE resulted in a significant decrease of CYP2C6 expression level by 68% (p<0.001). In case of CYP3A1 and CYP3A2, the mRNA levels were also reduced by extract but in a lesser degree compared to CYP2C6. Simultaneously the significant increase in the mRNA level of CAR, RXR and GR factors was observed by 54% (p<0.05), 79% (p<0.001) and 23% (p<0.05), respectively after 10 days of green tea extract administration. In addition, there was noted a small increase of CYP1A1 expression level by 21% (p>0.05) was noted. No statistically significant differences were observed for CYP1A2 and CYP2D1/2. In the same study we observed an increase in amount of ARNT gene transcript by 27% (p<0.05) in the long-term use. However, green tea extract showed the ability to stimulate HNF-1α both after 3 and 10 days of treatment by 30% (p<0.05) and 80% (p<0.001), respectively. In contrast, no change was observed in the concentration of HNF-4α cDNA. These results suggest that GTE may change the expression of CYP enzymes, especially CYP2C6 (homologue to human CYP2C9) and may participate in clinically significant interactions with drugs metabolized by these enzymes.

Open access

Agnieszka Gryszczyńska, Bogna Opala, Zdzisław Łowicki, Anna Krajewska-Patan, Waldemar Buchwald, Bogusław Czerny, Sebastian Mielcarek, Dariusz Boroń, Anna Bogacz and Przemysław M. Mrozikiewicz

Summary

The aim of our study were qualitative and quantitative analyses of two polyphenolic acids: chlorogenic and gallic acids. These compounds were determined in two species of Rhodiola: R. kirilowii and R. rosea. After collecting plants, aqueous and hydroalcoholic extracts were prepared. In order to identify analysed polyphenolic compounds ultra performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS, Waters) was used. Gallic acid is commonly found in the roots of these plants. Aqueous extract in both species is a rich source of gallic acid. The UPLC-MS/MS studies allow to use this analytical method for determination of polyphenolic acids accordance with the requirements of ICH. Chromatographic method developed by our team is more precise then previously published.

Open access

Agnieszka Gryszczyńska, Zdzisław Łowicki, Bogna Opala, Anna Krajewska-Patan, Waldemar Buchwald, Bogusław Czerny, Sebastian Mielcarek and Przemysław M. Mrozikiewicz

Summary

In our research, the concentration of lotaustralin in the roots of two species Rhodiola kirilowii and Rhodiola rosea were compared. Aqueous and hydroalcoholic extracts from those plants were analyzed too. To determine the content of this compound the ultra performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS, Waters) was used. The obtained results showed that the content of measured lotaustralin depends on the species of Rhodiola. R. rosea roots are the richer source of lotaustralin then R. kirilowii. The same situation was observed in the extracts. A hydroalcoholic extract from R. rosea contains up to 135.276 mg of lotaustralin in 100 g of dry powdered material. In the case of R. kirilowii extracts, an aqueous extract contained more lotaustralin (74.791 mg/100 g of dry powdered material) then a hydroalcoholic extract.

Open access

Agnieszka Gryszczyńska, Bogna Opala, Anna Krajewska-Patan, Zdzisław Łowicki, Waldemar Buchwald, Sebastian Mielcarek, Anna Bogacz, Monika Karasiewicz, Dariusz Boroń, Bogusław Czerny and Przemysław M. Mrozikiewicz

Summary

The aim of the study was the identification and quantitative analysis of phenylpropanoid compounds in the roots of Rhodiola species. Rosavin, rosarin and rosin were determined in the roots of R. kirilowii and R. rosea from the field cultivation, Institute of Natural Fibres and Medicinal Plants. For the quantitative analysis, the ultra performance liquid chromatography - tandem mass spectrometry (UPLC-ESI MS/MS, Waters) was used. The results showed differences in the quantitative and qualitative assessments of these two species. In the root of R. kirilowii the presence of phenylpropanoids was not confirmed. In R. rosea the most common phenylpropanoid was rosavin (0.022%). The UPLC-MS/MS studies allowed to use this analytical method for determination of phenylpropanoids in the accordance with the requirements of ICH.

Open access

Anna Bogacz, Donata Deka-Pawlik, Joanna Bartkowiak-Wieczorek, Monika Karasiewicz, Radosław Kujawski, Aleksandra Kowalska, Aleksandra Chałas, Bogusław Czerny, Edmund Grześkowiak and Przemysław M. Mrozikiewicz

Abstract

P-glycoprotein (P-gp) encoded by the MDR1 (multidrug resistance 1) gene is ATP-dependent transporting protein which is localizated in the cell membrane. P-gp is expressed mainly in organs with the secretory functions and its physiological role concerns tissue protection against xenobiotics. P-glycoprotein is involved in the permeability barriers of the blood-brain, blood-placenta directly protecting these organs. It participates in the transport of many drugs and other xenobiotics affecting their absorption, distribution, metabolism and excretion. The high P-gp activity in the cell membranes of cancer tissue is a major cause of lack of effectiveness of chemotherapy. Hence, the methods which could increase the sensibility of these pathological cells to cytostatics are still being searched. In the experimental studies it was shown that natural plant substances may have an effect on the expression level and activity of P-glycoprotein. Hypericum perforatum, Ginkgo biloba and Camellia sinensis increase P-gp activity while curcumin from Curcuma longa, piperine and silymarin inhibit this protein. Taking into account a wide substrate spectrum of P-gp, application of our knowledge on interactions of herbals and synthetic drugs should be considered in order to improve drug impact on different tissues.