THC-Reduced Cannabis sativa L.-How Does the Solvent Determine the Bioavailability of Cannabinoids Given Orally?

The bioavailability levels of cannabidiol (CBD) and tetrahydrocannabinol (THC) determine their pharmacological effects. Therefore, for medical purposes, it is essential to obtain extracts containing the lowest possible content of the psychogenic component THC. In our extract, the CBD/THC ratio was 16:1, which is a high level compared to available medical preparations, where it is, on average, 1:1. This study assessed the bioavailability and stability of CBD and THC derived from Cannabis sativa L. with reduced THC content. The extract was orally administered (30 mg/kg) in two solvents, Rapae oleum and Cremophor, to forty-eight Wistar rats. The whole-blood and brain concentrations of CBD and THC were measured using liquid chromatography coupled with mass spectrometry detection. Much higher concentrations of CBD than THC were observed for both solvents in the whole-blood and brain after oral administration of the Cannabis sativa extract with a decreased THC content. The total bioavailability of both CBD and THC was higher for Rapae oleum compared to Cremophor. Some of the CBD was converted into THC in the body, which should be considered when using Cannabis sativa for medical purposes. The THC-reduced hemp extract in this study is a promising candidate for medical applications.

The Dark Side of Iron: The Relationship between Iron, Inflammation and Gut Microbiota in Selected Diseases Associated with Iron Deficiency Anaemia-A Narrative Review.

Iron is an indispensable nutrient for life. A lack of it leads to iron deficiency anaemia (IDA), which currently affects about 1.2 billion people worldwide. The primary means of IDA treatment is oral or parenteral iron supplementation. This can be burdened with numerous side effects such as oxidative stress, systemic and local-intestinal inflammation, dysbiosis, carcinogenic processes and gastrointestinal adverse events. Therefore, this review aimed to provide insight into the physiological mechanisms of iron management and investigate the state of knowledge of the relationship between iron supplementation, inflammatory status and changes in gut microbiota milieu in diseases typically complicated with IDA and considered as having an inflammatory background such as in inflammatory bowel disease, colorectal cancer or obesity. Understanding the precise mechanisms critical to iron metabolism and the awareness of serious adverse effects associated with iron supplementation may lead to the provision of better IDA treatment. Well-planned research, specific to each patient category and disease, is needed to find measures and methods to optimise iron treatment and reduce adverse effects.

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.

Effect of Salvia miltiorrhiza root extract on brain acetylcholinesterase and butyrylcholinesterase activities, their mRNA levels and memory evaluation in rats.

Salvia miltiorrhiza (Lamiaceae), one of the most important and popular plants of traditional medicine of Asia, is used for the prevention and treatment of cardiovascular diseases and in central nervous system disturbances. The main aim of this study was to assess the influence of subchronic (28-fold) administration of Salvia miltiorrhiza root extract (SE, 200mg/kg, p.o.) on behavioural activity and memory of rats and to evaluate the activities of cholinesterases (AChE and BuChE) and gene expression levels of AChE and BuChE as well as of beta-secretase (BACE1) in the hippocampus and frontal cortex in vivo. Huperzine A (HU, 0.5mg/kg b.w., p.o.) served as a positive control substance, whereas scopolamine (0.5mg/kg, i.p.) injection was used as a well-known model of memory impairment. The results showed that subchronic administration of SE led to an improvement of long-term memory of rats. Strong inhibition of AChE and BuChE mRNA transcription in the frontal cortex of rats treated with SE or HU was observed. The BACE1 transcript level was significantly decreased. AChE activity was statistically significantly inhibited in the frontal cortex and the hippocampus by SE (47% and 55%, respectively). Similar effects were observed in the case of HU. In summary, activity of SE provides evidence that the plant can be a source of drugs used in the treatment of Alzheimer disease.

Influence of the Melissa officinalis Leaf Extract on Long-Term Memory in Scopolamine Animal Model with Assessment of Mechanism of Action.

Melissa officinalis (MO, English: lemon balm, Lamiaceae), one of the oldest and still most popular aromatic medicinal plants, is used in phytomedicine for the prevention and treatment of nervous disturbances. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 50% ethanol extract of MO leaves (200 mg/kg, p.o.) compared with rosmarinic acid (RA, 10 mg/kg, p.o.) and huperzine A (HU, 0.5 mg/kg, p.o.) on behavioral and cognitive responses in scopolamine-induced rats. The results were linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex of rats. In our study, MO and HU, but not RA, showed an improvement in long-term memory. The results were in line with mRNA levels, since MO produced a decrease of AChE mRNA level by 52% in the cortex and caused a strong significant inhibition of BACE1 mRNA transcription (64% in the frontal cortex; 50% in the hippocampus). However, the extract produced only an insignificant inhibition of AChE activity in the frontal cortex. The mechanisms of MO action are probably more complicated, since its role as a modulator of beta-secretase activity should be taken into consideration.

Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study.

Eryngium planum L. (EP) is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o.) on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU), scopolamine (SC) was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins) in the extract of EP roots.

The influence of standardized Valeriana officinalis extract on the CYP3A1 gene expression by nuclear receptors in in vivo model.

Valeriana officinalis is one of the most popular medicinal plants commonly used as a sedative and sleep aid. It is suggested that its pharmacologically active compounds derived from the root may modulate the CYP3A4 gene expression by activation of pregnane X receptor (PXR) or constitutive androstane receptor (CAR) and lead to pharmacokinetic herb-drug interactions. The aim of the study was to determine the influence of valerian on the expression level of CYP3A1 (homologue to human CYP3A4) as well as nuclear receptors PXR, CAR, RXR, GR, and HNF-4α. Male Wistar rats were given standardized valerian extract (300 mg/kg/day, p.o.) for 3 and 10 days. The expression in liver tissue was analyzed by using real-time PCR. Our result showed a decrease of CYP3A1 expression level by 35% (P = 0.248) and 37% (P < 0.001), respectively. Moreover, Valeriana exhibited statistically significant reduction in RXR (approximately 28%) only after 3-day treatment. We also demonstrated a decrease in the amount HNF-4α by 22% (P = 0.005) and 32% (P = 0.012), respectively. In case of CAR, the increase of expression level by 46% (P = 0.023) was noted. These findings suggest that Valeriana officinalis extract can decrease the CYP3A4 expression and therefore may lead to interactions with synthetic drugs metabolized by this enzyme.

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.

Screening for impact of popular herbs improving mental abilities on the transcriptional level of brain transporters.

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.

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.

Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain.

Rosmarinus officinalis L. leaf as part of a diet and medication can be a valuable proposal for the prevention and treatment of dementia. The aim of the study was to assess the effects of subchronic (28-fold) administration of a plant extract (RE) (200 mg/kg, p.o.) on behavioral and cognitive responses of rats linked with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity and their mRNA expression level in the hippocampus and frontal cortex. The passive avoidance test results showed that RE improved long-term memory in scopolamine-induced rats. The extract inhibited the AChE activity and showed a stimulatory effect on BuChE in both parts of rat brain. Moreover, RE produced a lower mRNA BuChE expression in the cortex and simultaneously an increase in the hippocampus. The study suggests that RE led to improved long-term memory in rats, which can be partially explained by its inhibition of AChE activity in rat brain.

[The influence of a standardized soybean extract (Glycine max) on the expression level of CYP3A enzymes and pregnane X receptor in in vivo model]. / Wplyw standaryzowanego ekstraktu sojoweg (Glycine max) na poziom ekspresji enzymów CYP3A i receptora pregnanu X w modelu in vivo.

OBJECTIVE: Soybean phytoestrogens, such as genistein and daidzein, have become a popular alternative for women undergoing the treatment of menopause symptoms. These isoflavones are also commonly used in traditional medicine in the prevention and treatment of osteoporosis, cardiovascular diseases and cancer Despite the widespread use of soybean preparations as functional foods and dietary supplements, data regarding the safety as well as interactions between herbal medicines and synthetic drugs, especially with antineoplastic agents, remain scarce. Therefore, the aim of the present study was to determine the influence of soybean extract on the expression levels of CYP3A and PXR genes using real-time PCR (RT-PCR). MATERIALS AND METHODS: Male Wistar rats were given a standardized soybean extract (100 mg/kg p.o.) for 3 and 10 days. Total RNA isolated from the liver tissue was transcribed into cDNA. The level of CYP3A 1/2 and PXR mRNAs expression was analyzed by real-time quantitative PCR using SYBR Green I dye. RESULTS: Our findings showed that soybean extract containing 37% isoflavones resulted in a significant decrease of CYP3A1 expression level by almost 35% (p<0.05), both after 3 and 10 days, when compared with the control group. No statistically significant differences were noted for CYP3A2 enzyme and the PXR nuclear factor. CONCLUSIONS: These results suggest that soybean extract can decrease the CYP3A1 (homolog to human CYP3A4) expression and may participate in clinically significant interactions with drugs metabolized by CYP3A4 enzyme. Moreover it is postulated that gene expression of CYP3A1 and CYP3A2 (homolog to human CYP3A5) can be regulated indirectly by the PXR transcription factor.

[Low back pain in pregnant women]. / Dolegliwosci bólowe dolnego odcinka kregoslupa u kobiet w ciazy.

Pain of lumbosacral segment of the vertebral column and the pelvis concerns about 45% of all pregnant women. The change of the body posture during pregnancy is the result of gravity centre relocation, which affects the musculosceletal system. Development of the joint, ligament and myofascial dysfunctions, as well as the pain in the lumbosacral segment and the pelvis, are the most common reasons of spine pain. The aim of this review is to present the current state of knowledge about lumbar spine pain in pregnant women with special focus on the pain connected with muscular, joint and ligament disorders. Pregnancy is a serious burden for the female osteo-skeletal system. Lumbar pain with different location and intensification is the negative consequence of the position changes during pregnancy. Pharmacotherapy could be useful only in cases of intensive low back pain, with possible application of small spectrum of drugs that are safe during pregnancy. Physical therapy including manual therapy exercises, massage and techniques of local anesthesia are alternative methods in case of low back pain in pregnant women.

[The role of phytoestrogen therapy in relieving postmenopausal symptoms]. / Rola terapii fitoestrogenowej w lagodzeniu dolegliwosci u kobiet po menopauzie.

Side effects and contraindications connected with hormonal replacement therapy in climacterium resulted in search for new methods of softening menopausal symptoms. The aim of the following study was to evaluate, based on literature analysis, the effectiveness of phytohormonal therapy as an alternative method of relieving the symptoms of menopausal period and preventing the diseases connected with deficiency of estrogens after menopause. Phytoestrogens therapy reduces the number and strength of the vasomotor symptoms and improves serum lipid profile. Moreover phytoestrogens show beneficial effects on bone tissue metabolism, skin and mucous membranes condition and are applicable in chemoprevention. This therapy is an effective method, allowing to avoid further changes in blood and urogenital systems, which result from estrogen stimulation deficiency. Phytoestrogens administration is an efficient method of relieving postmenopausal symptoms, facilitating the difficult menopausal period and keeping good health condition.