The Dual Faces of Oestrogen: The Impact of Exogenous Oestrogen on the Physiological and Pathophysiological Functions of Tissues and Organs.

Oestrogen plays a crucial physiological role in both women and men. It regulates reproductive functions and maintains various non-reproductive tissues through its receptors, such as oestrogen receptor 1/oestrogen receptor α (ESR1/Erα), oestrogen receptor 2/oestrogen receptor ß (ESR2/Erß), and G protein-coupled oestrogen receptor 1 (GPER). This hormone is essential for the proper functioning of women's ovaries and uterus. Oestrogen supports testicular function and spermatogenesis in men and contributes to bone density, cardiovascular health, and metabolic processes in both sexes. Nuclear receptors Er-α and Er-ß belong to the group of transcription activators that stimulate cell proliferation. In the environment, compounds similar in structure to the oestrogens compete with endogenous hormones for binding sites to receptors and to disrupt homeostasis. The lack of balance in oestrogen levels can lead to infertility, cancer, immunological disorders, and other conditions. Exogenous endocrine-active compounds, such as bisphenol A (BPA), phthalates, and organic phosphoric acid esters, can disrupt signalling pathways responsible for cell division and apoptosis processes. The metabolism of oestrogen and its structurally similar compounds can produce carcinogenic substances. It can also stimulate the growth of cancer cells by regulating genes crucial for cell proliferation and cell cycle progression, with long-term elevated levels linked to hormone-dependent cancers such as breast cancer. Oestrogens can also affect markers of immunological activation and contribute to the development of autoimmune diseases. Hormone replacement therapy, oral contraception, in vitro fertilisation stimulation, and hormonal stimulation of transgender people can increase the risk of breast cancer. Cortisol, similar in structure to oestrogen, can serve as a biomarker associated with the risk of developing breast cancer. The aim of this review is to analyse the sources of oestrogens and their effects on the endogenous and exogenous process of homeostasis.

Relationship between adipocytokines and angiotensin converting enzyme gene insertion/deletion polymorphism in lean women with and without polycystic ovary syndrome.

This study was designed to investigate the relationship between the levels of select adipocytokines (adiponectin, visfatin and apelin) and angiotensin in converting enzyme (ACE) gene insertion/deletion (ID) polymorphism in lean women with and without polycystic ovary syndrome (PCOS). The PCOS group (N = 94) was identified according to the Rotterdam criteria. The Control group (N = 68) included age- and body mass index (BMI)-matched healthy volunteers. Serum levels of adipocytokines were measured using enzyme immunoassays (EIA) and ACE genes were evaluated by polymerase chain reaction (PCR). The PCOS group, when compared to the Control group had lower adiponectin (p < .001) but higher visfatin (p < .001) and apelin (p = .003). There was no significant correlation of the levels of these adipocytokines with BMI, fasting glucose, fasting insulin or Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The PCOS and the Control groups also differed with regard to the ACE ID genotype distribution (p < .001). The ID, DD, and II genotype frequencies were, respectively, 34, 57 and 9% in the PCOS group and 49, 22 and 29% in the Control group. When stratified according to individual ID genotypes, the levels of adipocytokines in the PCOS and the Control groups remained significantly different. There was no statistically significant relationship between the levels of adipocytokines and ACE ID genotypes.

The Effect of Different Water Extracts from Platycodon grandiflorum on Selected Factors Associated with Pathogenesis of Chronic Bronchitis in Rats.

The aim of this study was to assess the activity of extracts from Platycodon grandiflorum A. DC (PG) in a model of chronic bronchitis in rats. The research was carried out on three water extracts: E1 - from roots of field cultivated PG; E2 - from biotransformed roots of PG; E3 - from callus of PG. The extracts differed in saponins and inulin levels-the highest was measured in E3 and the lowest in E1. Identification of secondary metabolites was performed using two complementary LC-MS systems. Chronic bronchitis was induced by sodium metabisulfite (a source of SO2). Animals were treated with extracts for three weeks (100 mg/kg, intragastrically) and endothelial growth factor (VEGF), transforming growth factors (TGF-ß1, -ß2, -ß3), and mucin 5AC (MUC5AC) levels were determined in bronchoalveolar lavage fluid, whereas C reactive protein (CRP) level was measured in serum. Moreover, mRNA expression were assessed in bronchi and lungs. In SO2-exposed rats, an elevation of the CRP, TGF-ß1, TGF-ß2, VEGF, and mucin was found, but the extracts' administration mostly reversed this phenomenon, leading to control values. The results showed a strong anti-inflammatory effect of the extracts from PG.

Demographic factors determining folic acid supplementation in pregnant and childbearing age women.

OBJECTIVES: Adequate folate intake constitutes a significant problem in the periconceptional period and early pregnancy but can be achieved by folic acid (FA) supplementation. Low intake of folate may cause numerous negative effects on the pregnancy outcome, including recurrent miscarriage, preeclampsia, fetal hypotrophy, premature delivery, premature placental abruption, and intrauterine fetal death. The aim of the study was to evaluate factors determining FA supplementation in the population of Polish women before and during pregnancy. MATERIAL AND METHODS: The study group consisted of 257 women hospitalized postpartum at the Division of Perinatology and Women's Diseases, Poznan University of Medical Sciences, Poland. We evaluated folic acid intake considering selected demographic data. A structured questionnaire was used to evaluate folic acid intake before and during pregnancy of the investigated women. RESULTS: The vast majority of the investigated women (89.1%) took FA during pregnancy. During the pre-pregnancy period, a statistically significantly higher supplementation of folic acid was observed among women with the monthly income level of > 5000 PLN (p = 0.03), and among women who planned their pregnancy as compared to women who did not plan their pregnancy (p < 0.001). During pregnancy, these differences disappeared. A statistically significantly higher number of secundi- and multiparas did not take FA during pregnancy as compared to primiparas (p = 0.008). No correlation between cigarette smoking and FA intake was observed. CONCLUSIONS: Our analysis showed that FA intake increased (by 36.2%) during pregnancy as compared to the pre-pregnancy period, and depended on income, parity, and pregnancy planning.

The importance of polymorphic variants of collagen 1A2 gene (COL1A2) in the development of osteopenia and osteoporosis in postmenopausal women.

OBJECTIVES: Collagen type I plays an important role in the bone matrix and is encoded by COL1A2 (collagen type I alpha 2) gene that may be a potential candidate for osteoporotic fracture. The aim of this study is to determine whether EcoRI, Del38 and PvuII polymorphisms of COL1A2 are associated with the development of osteoporosis and osteopenia in post-menopausal Polish women. Moreover, analysis of relationship between frequency of COL1A2 gene polymorphic variants and clinical parameters of bone turnover and degree of osteoporosis was performed. MATERIAL AND METHODS: The study group comprised of women with osteoporosis (n = 90), osteopenia (n = 56) and healthy individuals (n = 56). The EcoRI, Del38 and PvuII polymorphisms in COL1A2 gene were detected by PCR-RFLP method. RESULTS: In women with osteoporosis the TT genotype of EcoRI polymorphism had the lowest Z-score value compared to other genotypes (p = 0.034). In case of Del28 polymorphism, there was a statistically significant correlation between lower BMI values and the DD genotype in women with osteopenia (p = 0.041). There was no statistically significant correlation between polymorphic variants of Del28 polymorphism and clinical parameters of women with osteoporosis. The analysis of PvuII polymorphism showed that in women with osteopenia the CC genotype had the lowest body weight compared to other genotypes (p = 0.039). PvuII polymorphism and clinical parameters in the group of women with osteoporosis had no statistically significant correlations. CONCLUSIONS: The analyzed COL1A2 polymorphisms seem to be related to osteoporosis development and their particular clinical parameters. Hence, the COL1A2 polymorphism may be a genetic risk factor related to the development of osteoporosis.

Is there an association between the development of metabolic syndrome in PCOS patients and the C677T MTHFR gene polymorphism?

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is characterized by anovulation, polycystic ovaries, hyperandrogenism leading to infertility, dermatological and psychological problems, as well as the risk of developing Metabolic Syndrome (MetS) and cardiovascular disease (CVD). The exact cause of PCOS remains unclear. Various biochemical and genetic markers have been implicated in predisposition to PCOS, but no single variant has been associated with the syndrome. Some authors connect hyperhomocysteinemia (HHcy) with MetS and its components. The MTHFR gene C677T polymorphism is a common genetic abnormality leading to hyperhomocysteinemia. OBJECTIVES: The aim of the study was to confirm the existence of a possible correlation between metabolic disturbances in PCOS and the MTHFR C677T polymorphism. MATERIAL AND METHODS: A total of 98 patients diagnosed with PCOS according to the Rotterdam criteria and 101 age-matched healthy controls were included in the study. Genotyping of MTHFR C677T was performed by the real time PCR method. RESULTS: Statistically significant differences were observed between those two groups with regard to body mass index (BMI), waist circumference (WC), hip circumference (HC), fasting insulin, total cholesterol (TC), and triglycerides (TG). No significant differences in the prevalence of the genotypes of the MTHFR C677T gene polymorphism were found between the PCOS group and controls. Despite the lack of significant differences, we observed a tendency for a higher prevalence of the TT genotype in the PCOS group (p = 0.06). No statistically significant differences were observed between the PCOS group and the control group in terms of the presence of the MetS components and the predisposition to develop MetS. CONCLUSIONS: Our study did not confirm an association between the MTHFR C677T gene polymorphism and the development of MetS in PCOS. Further studies with larger sample size might be useful to determine this association.

The RANKL/RANK/OPG signal trail: significance of genetic polymorphisms in the etiology of postmenopausal osteoporosis.

OBJECTIVES: Recent studies have demonstrated that disorders of bone metabolism, which is regulated by RANK/RANKL/OPG signaling pathway, are the cause of osteoporosis. The aim of the study was to investigate the distribution of genotypes of the RANK 575C>T and RANKL -643C>T polymorphisms and to analyze their relationship with bone parameters in postmenopausal women. MATERIAL AND METHODS: A total of 310 postmenopausal Caucasian women (139 with osteoporosis, 107 with osteopenia, and 64 healthy postmenopausal controls) were included. Bone mineral density (BMD) at the lumbar region of the spine (L2-L4) was measured by dual energy X-ray absorptiometry (DXA). Genetic analysis was performed using the PCR-RFLP method. RESULTS: Analysis of the frequency of genotypes and alleles of the RANK 575C>T and RANKL -643C>T polymorphisms did not show any statistically significant differences between the study groups (osteoporosis and osteopenia) and postmenopausal women with normal t-score value (ns). Notably, a significant association between the RANKL -643C>T polymorphism and body mass, such as BMI values in osteoporotic women (p<0.05), was observed. CONCLUSIONS: Our results suggest lack of association between the 575C>T RANK polymorphism and the development of osteoporosis. The -643C>T RANKL polymorphism, through its significant influence on body weight and BMI value, may contribute to the development of osteoporosis in postmenopausal women.

Gender-specific implications for pharmacology in childbearing age and in postmenopausal women.

Women have three very important physiological functions that are not observed in men--menstruation, pregnancy and lactation. Each of these mechanisms influences pharmacokinetics and pharmacodynamics of many drugs. Individualization of pharmacotherapy is a major challenge of modern medicine. The differences in response to drug are responsible for the effectiveness of pharmacological treatment and the occurrence and severity of toxic effects and side effects. Therapeutic decision should be based not only on account of the dose-effect, but the consideration of gender, genetic and environmental differences affecting the final therapeutic effect. Many important differences between men and women like sex-based differences in normal physiology, or in the predisposition to a specific disease, can be due to genetic differences, the actions of the sex steroid hormones or an interaction between these factors. Women generally have a lower body mass, a reduced hepatic clearance, differences in activity of cytochrome P450 (CYP) enzymes (increase in CYP3A4, decrease in CYP2D6, CYP2C19 and CYP1A2) and different from men's rate of drug metabolism. Other important factors contributing to gender differences in the pharmacokinetics of drugs are conjugation, absorption, protein binding and urinary excretion. It still remains unexplained how gender differences affect the increased risk of side effects. This review is an attempt to assess the biological, physiological and hormonal basis of women differences in the pharmacokinetics and pharmacodynamics of many drugs.

[Polymorphism of bone morphogenetic protein (BMP2) and osteoporosis etiology]. / Polimorfizm bialka morfogenzntycznego kosci (BMP2) a etiologia osteoporozy.

OBJECTIVES: Osteoporosis is a chronic, generalized bone disease conditioned by many factors among which the genetic background plays the significant role. Bone morphogenetic protein (BMP2), a growth factor belong to su- perfamily of TNF- proteins, is actively involved in bone tissue metabolism. BMP2 protein shows the osteoinduction potential and regulates growth of cartilage plate, and the same directly influences the process of osteogenesis. THE AIM: The aim of study was to examine the frequency of genotypes and alleles of 570A>T and 5375G>A of BMP2 gene polymorphisms in population of Polish postmenopausal women, as well as to analyze the relationship between investigated polymorphic variants and bone turnover parameters. MATERIAL AND METHODS: Into the study 117 postmenopausal women, Caucasian race (average age 55,1 years) living in Wielkopolska region were classified. The analysis of 570A>T and 5375G>A BMP2 polymorphisms was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) while bone mineral density (BMD) was measured by DEXA method. In the research the chosen clinical and bone turnover parameters were analysed. RESULTS: In both 570A>T and 5375G>A BMP2 polymorphisms the similar frequency of genotypes and alleles in investigated groups of postmenopausal women with osteoporosis, osteopenia and in the group with correct T-score were noted. The analysis do not show the relationship of clinical and bone turnover parameters with particular genotypes of BMP2 polymorphisms in women with osteoporosis, osteopenia and in the group with correct T-score. CONCLUSIONS: The research did not confirm directly relationship of 570A>T and 5375G>A BMP2 polymorphisms with osteoporosis development in population of Polish postmenopausal women. The investigation also shows lack of correlation of 570A>T and 5375G>A BMP2 polymorphisms polymorphisms with analysed clinical and bone turnover parameters.

Polymorphisms of collagen 1A1 (COL1A1) gene and their relation to bone mineral density in postmenopausal women.

OBJECTIVES: The goal of this study was to evaluate the frequency of Sp1 +1245G>T (rs 1800012) and -199 7G>T (rs 1107946) COL1A1 gene polymorphisms in postmenopausal women with osteoporosis and osteopenia as well as assessing their relations with the clinical parameters and parameters of bone turnover. STUDY DESIGN: The study included 538 (236 postmenopausal and 302 healthy reproductive) Polish women. The postmenopausal group included women with osteoporosis (n = 90), osteopenia (n = 90), as well as healthy individuals (n = 56). All women of reproductive age were healthy BMD was marked in the L2-L4 lumbar region of the spine using dual energy X-ray absorptiometry (DXA). Genomic DNA was isolated from peripheral blood, the genotype frequency of investigated polymorphisms was determined by PCR-RFLP technique. RESULTS: The frequency of Sp1 +1245G>T and -1997G>T polymorphisms of COL1A1 gene showed no statistically significant differences between group with osteoporosis, osteopenia and correct T-score and women of reproductive age. In postmenopausal women it was found that osteopenia and osteoporosis were correlated with age, birth weight, age of last menses occurrence, height, body weight and BMI value. Clinical parameters in all groups of women did not show any statistically significant correlation with frequency of Sp1 +1245G>T and -1997G>T COL1A1 polymorphisms. CONCLUSIONS: An evaluation of Sp1 +1245G>T (rs1800012) and -1997G>T(rs 1107946) COL1A1 polymorphisms showed any influence of these genetic variants on osteoporosis development in Polish postmenopausal women. The presented correlation between osteoporosis and age, birth weight, age of last menses occurrence, height, body weight and BMI value confirms the important role of environmental factors in disease etiology.

The importance of rs1021737 and rs482843 polymorphisms of cystathionine gamma-lyase in the etiology of preeclampsia in the Caucasian population.

INTRODUCTION: Recently an increasing number of reports indicate the participation of genetic factors in the pathogenesis of preeclampsia (PE). The genes involved in the synthesis of nitric oxide that participates in the vasolidation, may play an important role in the development of this disorder. Hydrogen sulfide (H2S) which is produced by cystathionine gamma-lyase exhibits a similar effect to nitric oxide. It is suggested that certain polymorphisms of the CTH gene may participate in the development of chronic hypertension and preeclampsia. AIM OF THE STUDY: To evaluate the frequency of genotypes and alleles of rs1021737 and rs482843 polymorphisms of CTH gene in women with preeclampsia from Wielkopolska region. MATERIAL AND METHODS: The study group consisted of 60 patients with diagnosed preeclampsia, into the control group 120 healthy pregnant women were enrolled. The examined rs1021737 and rs482843 polymorphisms of CTH gene were determined using PCR-RFLP method. RESULTS: Analysis of rs482843 polymorphism in the CTH gene showed a statistically significant difference in the prevalence of mutated GG genotype (p<0.000001) and mutated G allele (p<0.000001) in the group of pregnant women with PE compared to the control group. There was no such correlation for the rs1021737 polymorphism. Furthermore, there are also no relationship between studied polymorphisms and selected clinical and biochemical parameters. CONCLUSIONS: The results of rs482843 polymorphism analysis suggest that mutated GG genotype predisposes to preeclampsia occurrence. There was no such relationship for the rs1021737 polymorphism of CTH gene. Hence, further studies based on the determination of CSE expression level in women with PE may confirm the observed relationship between the rs482843 polymorphism and the risk of preeclampsia.

Analysis of -11391G>A and +45>G polymorphisms of ADIPOQ gene in women with excessive weight gain during pregnancy.

OBJECTIVES: The aim of our study was to evaluate the frequency of genotypes and alleles of the -11391G>A and +45T>G polymorphisms of the ADIPOQ gene in Polish women with excessive weight gain during pregnancy. A possible correlation between these polymorphisms and selected clinical and anthropometric parameters has been analyzed. MATERIAL AND METHODS: A total of 153 pregnant Caucasian women of Polish origin with normal pre-pregnancy body mass were analyzed: 78 women with excessive weight gain (study group) and 75 women with normal weight gain during pregnancy (control group). The analysis of the polymorphisms was performed by PCR/RFLP. RESULTS: The influence of the -11391G>A polymorphism on body mass and BMI values at the end of pregnancy (p < 0.05) was observed. We also detected a correlation of the +45T>G polymorphism with body mass at the end of pregnancy and pre-pregnancy WHR values (p < 0.05). CONCLUSIONS: The observed effect of the -11391G>A polymorphism on the parameters assessed at the end of pregnancy (BMI and body mass), suggests a protective role of the -11391A genetic variant in excessive weight gain. It is claimed that the mutated +45G allele of the +45T>G ADIPOQ polymorphism shows a possible connection with higher pre-pregnancy WHR values and body mass at the end of pregnancy Our findings suggest a possible contribution of the -11391G>A and +45T>G polymorphisms of the ADIPOQ gene to the pathomechanism of excessive weight gain in pregnant women from the Polish population. This observation should be confirmed in a larger sample size study

Evaluation of anti-inflammatory and analgesic activities of extracts from herb of Chelidonium majus L.

The aim of the study was to evaluate analgesic activity ("hot plate" test), anti-inflammatory activity (carrageenan-induced paw edema) and locomotor activity in rats under the influence of three fractions of Chelidonium majus herb extract: full water extract (FWE), protein enriched fraction (PEF), and non-protein fraction (NPF). Effects of the fractions on the level of chosen cytokines and their mRNA levels were also assessed using lipopolysaccharide (LPS) administration as a proinflammatory cue. All fractions and diclofenac did not affect the locomotor activity of rats in comparison with the control group. FWE and PEF three hours after administration showed statistically significant analgesic activities comparable to morphine (p < 0.05). A slight reduction in rat paw edema was observed after three (comparable with diclofenac) and six hours in the NPF group. FWE revealed a statistically significant pro-inflammatory effect after three hours in comparison with the control group. Peripheral IL-1 and IL-4 cytokine concentrations were reduced under FWE and NPF, PEF fractions. The combination of FWE, PEF and NPF together with LPS showed only the effects of LPS. We suggest that protein enriched fraction (PEF) produced centrally mediated (morphine-like) analgesic action, whereas the anti-inflammatory potential was shown only after LPS-induced inflammation. The precise mechanisms involved in the production of anti-nociceptive and anti-inflammatory responses of studied fractions are not completely understood, but they may be caused rather by the presence of protein more than alkaloids-enriched fraction. This fraction of the extract could be used as an alternative therapy for the prevention of inflammatory-related diseases in the future, but further studies are needed.

The importance of 8993C>T (Thr399Ile) TLR4 polymorphism in etiology of osteoporosis in postmenopausal women.

INTRODUCTION: Toll-like receptors (TLR) may play a key role in initiating cellular signaling pathways by increasing the levels of inflammatory cytokines which, cooperating with osteoclasts, influence bone turnover Numerous research articles focused on the genetic background of this condition, among others on polymorphic variants in TLR genes. The aim of the study was to examine the role of 20877G>A (Arg753GIn) in TLR2 gene and 8993C>T (Thr399lle) in TLR4 gene in the etiopathogenesis of postmenopausal osteoporosis in Polish women. MATERIAL AND METHODS: This study included 180 postmenopausal women (t-score < or = -2.5), 153 postmenopausal women with osteopenia (t-score between -2.5 and -1), and 91 postmenopausal healthy women with correct t-score (t-score >-1). The 20877G>A TLR2 and 8993C>T TLR4 polymorphisms were determined by PCR/RFLP analysis. RESULTS: The analysis did not reveal statistically significant differences in the distribution of genetic variants of 20877G>A TLR2 polymorphism between the investigated groups of women. The most interesting results were connected with 8993C>T TLR4 polymorphism. Comparison of the group with osteoporosis and controls revealed overrepresentation of heterozygous 8993CT genotype (13.3 vs. 5.5%, OR=2.65, p=0.03). Also, mutated 8993T allele was overrepresented in the group with osteoporosis (6.7 vs. 2.7%, OR=2.52, p=0.04). Higher frequency of heterozygous 8993CT genotype (13.3 vs. 4.6%, OR=3.21, p=0.004) and mutated 8993T allele (6.7 vs. 2.3%, OR=3.05, p=0. 005) was noted in osteoporotic women as compared to the group with osteopenia. Higher frequency of heterozygous 8993CT genotype (13.3% vs. 5.3%, OR=2.73, p=0.003) and mutated 8993T allele (6.7 vs. 2.7%, OR=2.67, p=0.004) was observed in the group with osteoporosis as compared to women with osteopenia and with correct t-score. CONCLUSIONS: Results of our study suggest an important role of mutated 8993T allele of 8993C>T TLR4 polymorphisms in the etiology of postmenopausal osteoporosis. Nevertheless, this observation requires further investigation with larger sample size comprised of Polish women.

Effect of Epilobium angustifolium and Serenoa repens extracts on regulation of non-genomic signaling pathway of kinases.

OBJECTIVES: Changes of kinase activity of non-genomic cellular signaling pathway may influence the effectiveness of pharmacotherapy in case of hormone-dependent tumors. Our study investigated a possible interaction at the molecular level between an aqueous herbal extract of Epilobium angustifolium as well as a lipid-sterolic fruit extract of Serenoa repens and synthetic drugs used in the treatment of hormone-dependent cancers. MATERIAL AND METHODS: E. angustifolium and Serenoa repens extracts were orally administered to testosterone-induced rats for 21 days. Changes of RafA/Mapk3/Mapk1 mRNA levels were analyzed by real-time quantitative PCR using target specific primers. RESULTS: The level of RafA mRNA slightly increased in rats receiving Epilobium angustifolium (p = 0.076) and Serenoa repens (p = 0.016) extracts. Administration of these extracts resulted in significantly elevated Mapk1 and Mapk3 transcripts in the investigated animals (p < 0.05 for each extract). The levels of Mapk1 and Mapk3 mRNA strongly increased (p < 0.05 for each extract) in animals receiving concomitantly testosterone and the extracts, while RafA transcription slightly decreased (p < 0.05), as compared to controls. CONCLUSIONS: The results of our study may indicate a potential effect of S. repens and E. angustifolium extracts on the functioning of non-genomic cellular signaling kinases pathway. We investigated safety of these extracts to detect possible drug interactions between synthetic drugs used in the treatment of proliferative changes in hormone-dependent reproductive organs and herbal preparations.

The influence of soybean extract on the expression level of selected drug transporters, transcription factors and cytochrome P450 genes encoding phase I drug-metabolizing enzymes.

OBJECTIVE: Soybean phytoestrogens, such as genistein and daidzein, reduce climacteric symptoms and the risk of certain chronic diseases such as cancer and cardiovascular diseases. Despite their widespread use in functional foods and dietary supplements, there is very little data available on their safety and herb-drug interactions, especially with antineoplastic agents. Hence, the aim of our study was to assess the effects of soybean extracts on the expression level of CYP genes and their transcriptional factors. We also investigated the effect of soybean on the mRNA level of transporters, such as P-glycoprotein (MDRI) and multidrug resistance-associated proteins (MRP1, MRP2). MATERIALS AND METHODS: Wistar rats were fed a standardized soybean extract (100 mg/kg, p.o.). cDNA was synthesized from total RNA isolated from different tissues (liver and intestinal epithelium) using reverse transcription. Gene expression level was analyzed by RT-PCR method. RESULTS: We demonstrated a significant increase of CYP1A1 mRNA level (by 89%, p = 0.002 and 125%, p = 0.004) as compared with the control group. An increase of AHR and CAR expression after 10 days was also observed (by 60%, p < 0.001 and 52%, p > 0.05, respectively). Additionally an inductive effect for CYP2D1 by 22% (p = 0.008), Mdr1a by 267% (p < 0.0001), Mdr2b by 86% (p < 0.00001), Mrp1 by 9-fold (p < 0.0001), Mrp2 by 83% (p < 0.0001) in the liver and for Mrp2 by 35% (p < 0.001) in the intestinal epithelium, was evaluated. A significant decrease of mRNA level was observed for CYP3A1 (human CYP3A4) in the liver and Mdr1b in the intestinal epithelium. Moreove, we also showed a slight decrease in the amount of mRNA for CAR, PXR and ARNT after 3 days. CONCLUSIONS: Our results suggest that Glycine max may change the expression level of CYPs, especially CYP3A4 and CYP1A 7, involved in biotransformation of xenobiotics (drugs, procarcinogens) and may participate in clinically significant interactions with drugs metabolized by these enzymes. Moreover an increase of CYP1A1 (homologue to human CYPIA 1) mRNA level may not only reduce the carcinogenicity of foreign compounds, but may also activate some compounds to their carcinogenicity In case of transporters, it is considered that an increase of their expression in the body may lead to increased fetoprotection. Also, it may reduce both, the exposure of sensitive tissues (e.g. brain, placenta) to xenobiotics and treatment effectiveness of certain diseases. Hence, the search for a safe substance that could effectively modulate transporter activity especially in the treatment of certain hormone -dependent disorders, e.g. osteoporosis and breast cancer occurring mainly in postmenopausal period, continues.

Natural Products and Health.

A natural product is an organic compound from a living organism that can be isolated from natural sources or synthesized [...].

Methylsulfinyl Hexyl Isothiocyanate (6-MSITC) from Wasabi Is a Promising Candidate for the Treatment of Cancer, Alzheimer's Disease, and Obesity.

Methylsulfinyl hexyl isothiocyanate (6-MSITC) isolated from Eutrema japonicum is a promising candidate for the treatment of breast cancer, colorectal and stomach cancer, metabolic syndrome, heart diseases, diabetes, and obesity due to its anti-inflammatory and antioxidant properties. Also, its neuroprotective properties, improving cognitive function and protecting dopaminergic neurons, make it an excellent candidate for treating neurodegenerative diseases like dementia, Alzheimer's, and Parkinson's disease. 6-MSITC acts on many signaling pathways, such as PPAR, AMPK, PI3K/AKT/mTOR, Nrf2/Keap1-ARE, ERK1/2-ELK1/CHOP/DR5, and MAPK. However, despite the very promising results of in vitro and in vivo animal studies and a few human studies, the molecule has not yet been thoroughly tested in the human population. Nonetheless, wasabi should be classified as a "superfood" for the primary and secondary prevention of human diseases. This article reviews the current state-of-the-art research on 6-MSITC and its potential clinical uses, discussing in detail the signaling pathways activated by the molecule and their interactions.

Cannabis sativa L. Extract Alleviates Neuropathic Pain and Modulates CB1 and CB2 Receptor Expression in Rat.

INTRODUCTION: Cannabis sativa L. (CSL) extract has pain-relieving potential due to its cannabinoid content, so the effects of two CSL extracts on alleviating neuropathic pain were investigated in vivo. Methods and groups: Male Wistar rats (n = 130) were divided into groups and received vincristine (0.1 mg/kg) and gabapentin (60 mg/kg) to induce and relieve neuropathic pain or CSL extracts (D and B). The mRNA and protein expression of the cannabinoid receptors type 1 and 2 (CB1R, CB2R) were evaluated in the cerebral cortex, hippocampus, and lymphocytes. Behavioural tests (Tail-Flick and von Frey) were performed on all animals. RESULTS: VK-induced neuropathic pain was accompanied by decreased CB1R protein level and CB2R mRNA expression in the cortex. Gabapentin relieved pain and increased CB1R protein levels in the hippocampus compared to the vincristine group. Hippocampus CB1R protein expression increased with the administration of extract D (10 mg/kg, 40 mg/kg) and extract B (7.5 mg/kg, 10 mg/kg) compared to VK group. In the cerebral cortex CSL decreased CB1R protein expression (10 mg/kg, 20 mg/kg, 40 mg/kg of extract B) and mRNA level (5 mg/kg, 7.5 mg/kg of extract B; 20 mg/kg of extract D) compared to the VK-group.CB2R protein expression increased in the hippocampus after treatment with extract B (7.5 mg/kg) compared to the VK-group. In the cerebral cortex extract B (10 mg/kg, 20 mg/kg) increased CB2R protein expression compared to VK-group. CONCLUSION: Alterations in cannabinoid receptor expression do not fully account for the observed behavioural changes in rats. Therefore, additional signalling pathways may contribute to the initiation and transmission of neuropathic pain. The Cannabis extracts tested demonstrated antinociceptive effects comparable to gabapentin, highlighting the antinociceptive properties of Cannabis extracts for human use.

Frequency of G2677T/A and C3435T polymorphisms of MDR1 gene in preeclamptic women.

OBJECTIVE: Preeclampsia (PE) belongs to main causes of mortality rates of mothers, fetuses and new born children. Polymorphism of MDR1 gene is connected with reduction of P-glycoprotein expression in placenta and increased fetal exposure to xenobiotics. The aim of the study was to determine the frequency of C3435T and G2677T/A polymorphisms of MDR1 gene in pregnant women with preeclampsia. MATERIALS AND METHODS: The study consisted of 180 Polish women including 60 women with PE and 120 healthy pregnant women. Determination of C3435T and G2677T/A polymorphisms of MDR1 gene was performed using PCR-RFLP method. RESULTS: No significant association between genotypes of the examined polymorphisms and the clinical parameters of pregnant women with PE was observed However the interesting tendency to higher prevalence of mutated 2677A allele of G2677T/A MDR1 polymorphism in PE group has been shown (2,50 vs. 0,83% in controls, OR=3,05, ns). CONCLUSIONS: The results of this study suggest no significant effect of examined C3435T and G2677T/A MDR1 polymorphisms in PE pathogenesis. However given the noteworthy results related to mutated 2677A allele of G2677T/A MDR1 polymorphism in preeclamptic women further studies seem to be needed. Nevertheless, the frequency of investigated polymorphisms was consistent with the distribution in other Caucasian populations.