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  • Author: Przemyslaw L. Mikolajczak x
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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

Michał Szulc, Piotr Mularczyk, Patryk Grządzielski, Przemysław Zakowicz, Radosław Kujawski, Agnieszka Gryszczyńska, Waldemar Buchwald, Artur Teżyk, Anna Krajewska-Patan, Ewa Kamińska and Przemysław Ł. Mikołajczak

Summary

Introduction: Rhodiola rosea (RR) and Rhodiola kirilowii (RK) are well known for their influence on central nervous system, however their impact on the development of alcohol tolerance has not yet been proven.

Objective: The aim of this study was to determine the ability of RR and RK roots extracts to inhibit the development of alcohol tolerance in vivo, both, peripheral (metabolic) and central ones.

Methods: Male Wistar rats were treated with RR and RK extracts (p.o.) and ethanol (i.p.) for ten consecutive days. On the first, third, fifth and eighth days the hypothermic action of ethanol was measured, while on the ninth day the loss of righting reflex was examined. On the tenth day rats were treated with assigned extract and sacrificed 1 h after the ethanol injection.

Results: Both extracts inhibited development of tolerance to the hypothermic action of ethanol. The observed effect seems to be specific since none of the extracts affected body temperature in water-treated animals. RK extract also prolonged the hypnotic action of ethanol. RR-treated rats had higher blood-ethanol concentrations, in contrast to RK ones.

Conclusions: RR and RK extracts inhibited the development of tolerance to the hypothermic action of ethanol. Prolongation of the hypnotic action of ethanol by RK extract may be associated with influence on the central nervous system, while the RR one also inhibited the development of metabolic tolerance.

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

Anna Bogacz, Monika Karasiewicz, Karolina Dziekan, Danuta Procyk, Małgorzata Górska-Paukszta, Aleksandra Kowalska, Przemysław Ł. Mikołajczak, Marcin Ożarowski and Bogusław Czerny

Summary

Introduction: Despite widespread use of Panax ginseng and Ginkgo biloba, the data on the safety as well as herb-drug interactions are very limited. Therefore, we postulate that P. ginseng and G. biloba may modulate the activity and content of cytochrome P450 isozymes involved in the biotransformation of diverse xenobiotic substances. Objective: The aim of our study was to determine the influence of herbal remedies on the expression level of CYP enzymes and transcriptional factors. Methods: Male Wistar rats were given standardized Panax ginseng (30 mg/kg p.o.) or standardized Ginkgo biloba (200 mg/kg p.o.) for 3 and 10 days. The expression in liver tissue was analyzed by realtime PCR method. Results: Our results showed a decrease of CYP3A1 (homologue to human CYP3A4) mRNA level after P. ginseng extract treatment. The CYP2C6 (homologue to human CYP2C9) expression was also reduced. Additionally, after 10 days of the treatment with P. ginseng an increase of CYP1A1 (homologue to human CYP1A1) and CYP1A2 (homologue to human CYP1A2) expression was observed. Moreover, G. biloba extract also caused an increase of expression level for CYP1A1, CYP2C6, CYP3A1 and CYP3A2. Conclusion: Our findings suggest that herbal extracts can modulate the expression of transcriptional factors and CYP enzymes involved in xenobiotic metabolism and chemical carcinogenesis.

Open access

Radosław Kujawski, Justyna Baraniak, Małgorzata Kania, Joanna Bartkowiak-Wieczorek, Anna Bogacz, Marcin Ożarowski, Michał Cichocki, Ewa Spoz and Przemysław Ł. Mikołajczak

Summary

In last centuries, human diet has been modified due to changes in the technological, economic, and cultural mode of the social life. The rapid development of the technology and advances in food production and processing of plants resulted in changes in the structure of consumption. The consequence is an growing interest among researchers, but also among consumers in searching for new alternatives to classical pharmacology, preventive solutions, and therapeutic strategies of age related, chronic diseases and cancer. In this paper, the authors have attempted to assess the benefits of usage in diet cold-pressed oils extracted from the seeds of Brassica napus (oilseed rape) with particular emphasis on the evidence of possible use of B. napus oil, and other bio-active substances contained therein, in the prevention and symptomatic treatment of prostate diseases, including benign prostatic hyperplasia (BPH). The authors postulate that the information presented in this paper may be important and helpful in the development of new, effective and safe forms of prevention and treatment of progressive age-related disorders (phytotherapeutics) and nutritional strategies (dietary supplements) based on seeds oil of Brassicace family representatives, especially Brassica napus (pollen).

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

Michał Szulc, Piotr Mularczyk, Radosław Kujawski, Agnieszka Gryszczyńska, Ewa Kamińska, Bogna Geppert, Justyna Baraniak, Małgorzata Kania-Dobrowolska, Marcin Ożarowski, Anna Krajewska-Patan and Przemysław Ł. Mikołajczak

Summary

Introduction: In recent years, the search for potential neuroprotective properties of salidroside and its ability to influence the activity of nervous system become the subject of intense studies of many research groups. None of these studies, however, include an attempt to determine the effect of salidroside on the course of alcohol tolerance in vivo.

Objective: The aim of this study was to investigate the ability of salidroside to inhibit the development of alcohol tolerance in rats, determining whether the effect of its action may occur in a dose-dependent manner, reducing both metabolic and central tolerance without affecting body temperature in control rats.

Methods: Male Wistar rats were injected daily with ethanol at a dose of 3 g/kg for 9 consecutive days to produce ethanol tolerance. Salidroside in two doses (4.5 mg/kg and 45 mg/kg b.w.) or vehiculum was administered orally. On the 1st, 3rd, 5th and 8th day a hypothermic effect of ethanol was measured, while the loss of righting reflex procedure was performed on the 2nd, 4th, 6th and 7th day. On the 9th day rats were treated with salidroside, sacrificed 1 h after ethanol injections and blood was collected for blood-ethanol concentration measurement.

Results: Salidroside at a dose of 45 mg/kg inhibited the development of tolerance to hypothermic and sedative effects of ethanol, whereas insignificant elevation of blood-ethanol concentration was observed. The dose of 4.5 mg/kg b.w. had minimal effect, only small inhibition of tolerance to hypothermic action was observed. Salidroside affected neither body mass growth nor body temperature in non-alcoholic (control) rats.

Conclusions: Results of the study indicate that salidroside at a dose of 45 mg/kg inhibited the development of tolerance to the hypothermic effect of ethanol. Observed inhibition of tolerance to the sedative effect of ethanol seems to be associated with salidroside influence on the central nervous system. A comprehensive explanation of the abovementioned observations requires further pharmacological and pharmacodynamic studies.