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 (MDR1) 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%, p0.05, respectively). Additionally, an inductive effect for CYP2D1 by 22% (p=0.008), Mdr1a by 267% (

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 testosteroneinduced 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 (

Influence of standardized extract of Epilobium angustifolium on estrogen receptor α and β expression in in vivo model

Abstract Objective: Evaluation of the influence of the standardized extract from the herb of Epilobium angustifolium on ERα and ERβ mRNA expression in rat ventral prostate tissue and free serum estradiol level. Materials and methods: Rats were divided into 6 groups with 10 animals. ERα and ERβ mRNA expression in rat ventral prostate tissue level was performed using real-time PCR method in Light Cycler system. Serum-free estradiol was evaluated using immunoenzymatic technique. Results: In our experimental model there was an increase of ERα mRNA level by 9% and decrease by 36% of ERβ mRNA level in ventral prostate tissue in rats administrated with testosterone and E. angustifolium extract, in comparison with testosterone alone administrated animals. Conclusions: E. angustifolium standardized extract influenced the expression of estrogen receptor α and β mRNAs in differential manner which may suggest its potentially therapeutic properties or causing of adverse effects in pharmacotherapy of estrogen-related disorders. More complex studies should be undertaken to evaluate safety and to improve the efficacy of using this herbal extract

The influence of interleukin-6 and tumor necrosis factor α gene polymorphisms on bone mineral density in postmenopausal women

Summary Proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), involved into osteoclastogenesis and responsible for bone resorption process, participate in the pathogenesis of the osteoporosis. In vitro studies have shown that single nucleotide polymorphisms of IL-6 and TNF-α genes could influence the transcription process of the genes and the cytokines level. Aim: Assessment of the influence of IL-6 and TNF-α gene polymorphisms on bone mineral density (BMD) and evaluation of their connection with osteoporosis prevalence in women from Wielkopolska region. Material and methods: In the group of 267 postmenopausal women (average age 58,5+/-5,9 years, average age of last period 49,8+/-3,9 years) bone mineral density in lumbar spine (L2-L4) was performed using dual energy X-ray absorptiometry (DXA). Genotypes frequencies were determined by polymerase chain reaction with restriction fragment length polymorphism (PCR/RFLP) using restriction enzymes Lwe I and Faq I, respectively. The connection between the polymorphisms of investigated genes and body mass index, age of menarche and menopause and length of reproductive age had been analyzed as well. Results: No statistically significant association was found between examined genetic factors and the value of bone mineral density in the investigated group of postmenopausal women. The frequencies of investigated genotypes were in compliance with Hardy-Weinberg equilibrium. The correspondence between evaluated clinical parameters and IL-6 i TNF-α genotypes frequencies has not been proven. Conclusions: The -174G/C polymorphism in the IL-6 and -308G/A polymorphism in TNF-α genes have no influence on bone mineral density value (BMD) in the investigated population of women from Wielkopolska region

Wpływ kanabinoidów na układ wydzielania wewnętrznego

Kanabinnoidy stanowią pochodne konopii, najbardziej aktywnym biologicznie wśród nich jest tetrahydrokannabinol (THC). Najczęściej stosowanymi narkotykami są marihuana, haszysz i olej haszyszowy. Te mieszaniny związków wywierają swój efekt poprzez interakcję z receptorami kannabinoidowymi CB1 i CB2. Receptory typu pierwszego (CB1) zlokalizowane są głównie w ośrodkowym układzie nerwowym oraz w tkance tłuszczowej oraz narządach, w tym większości gruczołów wydzielania wewnętrznego. Receptory typu drugiego (CB2) znajdują się głównie w obwodowym układzie nerwowym (obwodowe zakońćzenia nerwowe) oraz na powierzchni komórek ukłądu immunologicznego. Obecnie coraz większą wagę przywiązuje się do roli endogennych ligandów oddziałujących ze wspomnianymi receptorami, jak i roli samych receptorów. Dotychczas udowodniono udział endogennych kannabinoidów w regulacji ilości przyjmowanego pokarmu, homeostazy, mają także istotny wpływ na układ wydzielania wewnętrznego, w tym aktywność przysadki, kory nadnerczy, tarczycy, trzustki i gonad. Wzajemne powiązania pomiędzy układem endokannabinoidowym i aktywnością układu wydzielania wewnętrznego może stanowić punkt uchwytu dla licznych leków, któych skuteczność wykazano w przypadku leczenia niepłodności, otyłości, cukrzycy cz nawet zapobieganiu chorobom układu sercowo-naczyniowego.

Association of Low Placental Growth Factor Gene Expression with Maternal and Neonatal Outcomes in Type 1 Diabetes: A Single Center, Cross-Sectional Study

Objective: The placental growth factor (PlGF) plays a crucial role in early and late pregnancy placental development. Pregestational type 1 diabetes (T1D) is a pregnancy complication that may lead to serious fetomaternal complications. Our study analyzed the association between placental PlGF mRNA expression and metabolic control, fetal weight and development in women with T1D. Materials and methods: A cross-sectional study on 65 pregnant women with T1D in singleton pregnancies admitted to the tertiary-level perinatal care unit. The study examined associations between the placental mRNA-PlGF gene expression measured with quantitative real-time PC and markers of maternal metabolism in the third trimester. The expression was also compared across maternal subgroups stratified according to the birth weight (small- vs. appropriate- vs. large-for-gestational age; SGA, AGA, LGA, respectively) and the following neonatal outcomes: mode of delivery, Apgar score and pH in the umbilical vessels. Results: Placental PlGF mRNA expression was significantly lower in SGA than in AGA and LGA patients (0.60 ± 0.34 vs. 0.63 ± 0.54 vs. 1.02 ± 0.15, respectively, p < 0.05). In the SGA group, the expression of the PlGF-mRNA correlated positively with maternal 3rd trimester BMI (r = 0.49, p = 0.04), pH and BE cord blood values, and maternal 3rd trimester mean BP. There was no correlation between 3rd-trimester glycated hemoglobin and mean blood glucose levels (MBG) and PlGF expression. Conclusions: Our data suggest that lower PlGF mRNA expression may predict neonatal outcomes in women with T1D giving birth to SGA newborns

A critical look at the new possibilities of therapeutic use of statins – a summary of the current state of knowledge

Hypercholesterolemia is a condition characterized by total cholesterol levels exceeding 200 mg/dl. A breakthrough in its treatment was the introduction of the first representative of the status - lovastatin. The mechanism of their action relies on inhibition of the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme responsible for converting HMG-CoA to mevalonic acid, the main substrate in the synthesis of endogenous cholesterol. The progress of experimental and clinical studies on action statins indicates a number of other biological properties of this group of compounds, and thus their pharmacological potential. The possibility of their use in the pharmacotherapy of cardiovascular diseases, hyperandrogenism in women with polycystic ovary syndrome (PCOS), osteoporosis, type 2 diabetes, neurodegenerative diseases, or cancer has been so far highlighted. The aim of this paper was to systematize the knowledge of statin drugs in terms of the progress of studies on their biological activity indicating the possibility of their potential use in the treatment of diseases other than those related to the cardiovascular system, along with verification of their safety profile and demonstrated adverse effects (DN) as a result of their intake. The literature review was conducted by a screening of the following scientific databases - PubMed and Google Scholar (the analysis lasted from March 2022 to February 2023). The keywords used for searching were disease-related and DN-related. Statins have shown potential to alleviate symptoms of androgen excess in women suffering from polycystic ovary syndrome (PCOS). Studies relating to their effect on the treatment of Alzheimer's disease and dementia indicate a reduction in progressive neurodegenerative changes, and thus suggest their potential use in the prevention and treatment of comorbid cardiovascular disease. Moreover, statins tend to reduce morbidity, increase survival, and alleviate the progression of cancer. The results of studies of the effects of these drugs on the possibility or development of Parkinson's disease, osteoporosis and the etiology of muscle symptoms appear to be inconsistent in the relationship of their benefits to DN. Unfortunately, it seems that they have also led to disturbances in carbohydrate metabolism and increased the risk of type II diabetes mellitus (NODM). Studies on the effect of the nocebo effect during statin therapy on the frequency with which patients experience DN have confirmed the presence of this effect. Analysis of the collected studies shows considerable potential for expanding the current therapeutic indications of the drugs in question. However, further randomized controlled trials are required to determine the precise effective dose, duration of therapy for a specific statin

CANNABINOIDS AS ANTIEMETICS: A SHORT REVIEW

Chemotherapy Induced Nausea and Vomiting (CINV) remains one of the most frequent adverse effects of cancer chemotherapy, often leading to patient non-adherence to the prescribed chemotherapeutic regime, as well as several associated complications. Current antiemetic therapy has been reported to provide relief of CINV in 75%-80% of patients, still leaving margin for improvement. This makes the development and study of novel antiemetics, especially those providing relief of both early and late phases of CINV, a matter of prime importance. The purpose of this review is to illustrate the mechanism of action of cannabinoid substances and provide a general view into their current use as antiemetic drugs in clinical practice. Several research articles pertaining the subject were compiled and studied. This review presents the information thereby obtained. It is concluded that cannabinoids possess value as antiemetic drugs, along with certain properties that set them apart from other classes of antiemetic substances

REVIEW ARTICLES Borage (Borago officinalis L.) -a valuable medicinal plant used in herbal medicine

S u m m a r y In Europe, the use of herbs in the treatment of various ailments had been natural for centuries. Nowadays, phytotherapy is a way to support typical pharmacotherapy of many diseases. Borage (Borago officinalis L.) is one out of more than 20 000 plants of therapeutic properties. The results of some studies indicate that Borago officinalis L. is commonly used adjunctively in disorders of the respiratory system, urinary tract, arthritis and skin problems. Biologically active compounds found in borage oil are used as additives in the treatment of atherosclerosis, as well as in the regulation of certain metabolic processes