Naringin and Naringenin: Their Mechanisms of Action and the Potential Anticancer Activities.

Naringin and naringenin are the main bioactive polyphenols in citrus fruits, the consumption of which is beneficial for human health and has been practiced since ancient times. Numerous studies have reported these substances' antioxidant and antiandrogenic properties, as well as their ability to protect from inflammation and cancer, in various in vitro and in vivo experimental models in animals and humans. Naringin and naringenin can suppress cancer development in various body parts, alleviating the conditions of cancer patients by acting as effective alternative supplementary remedies. Their anticancer activities are pleiotropic, and they can modulate different cellular signaling pathways, suppress cytokine and growth factor production and arrest the cell cycle. In this narrative review, we discuss the effects of naringin and naringenin on inflammation, apoptosis, proliferation, angiogenesis, metastasis and invasion processes and their potential to become innovative and safe anticancer drugs.

Influence of Technological Factors on the Quality of Chitosan Microcapsules with Boswellia serata L. Essential Oil.

Essential oils contain many volatile compounds that are not stable and lose their pharmacological effect when exposed to the environment. The aim of this study is to protect Boswellia serrata L. essential oil from environmental factors by encapsulation and determine the influence of chitosan concentration and types (2%, 4%; medium and high molecular weights), essential oil concentration, different emulsifiers (Tween and Span), and technological factors (stirring time, launch height, drip rate) on the physical parameters, morphology, texture, and other parameters of the generated gels, emulsions, and microcapsules. For the first time, Boswellia serrata L. essential oil microcapsules with chitosan were prepared by coacervation. Hardness, consistency, stickiness, viscosity, and pH of chitosan gels were tested. Freshly obtained microcapsules were examined for moisture, hardness, resistance to compression, size, and morphology. Results show that different molecular weights and concentrations of chitosan affected gel hardness, consistency, stickiness, viscosity, mobility, and adhesion. An increase in chitosan concentration from 2% to 4% significantly changed the appearance of the microcapsules. It was found that spherical microcapsules were formed when using MMW and HMW 80/1000 chitosan. Chitosan molecular weight, concentration, essential oil concentration, and stirring time all had an impact on the hardness of the microcapsules and their resistance to compression.

Cannabis sativa L. Bioactive Compounds and Their Protective Role in Oxidative Stress and Inflammation.

Cannabis (Cannabis sativa L.) plants from the family Cannabidaceae have been used since ancient times, to produce fibers, oil, and for medicinal purposes. Psychoactive delta-9-tetrahydrocannabinol (THC) and nonpsychoactive cannabidiol (CBD) are the main pharmacologically active compounds of Cannabis sativa. These compounds have, for a long time, been under extensive investigation, and their potent antioxidant and inflammatory properties have been reported, although the detailed mechanisms of their actions have not been fully clarified. CB1 receptors are suggested to be responsible for the analgesic effect of THC, while CB2 receptors may account for its immunomodulatory properties. Unlike THC, CBD has a very low affinity for both CB1 and CB2 receptors, and behaves as their negative allosteric modulator. CBD activity, as a CB2 receptor inverse agonist, could be important for CBD anti-inflammatory properties. In this review, we discuss the chemical properties and bioavailability of THC and CBD, their main mechanisms of action, and their role in oxidative stress and inflammation.

Natural Compounds Rosmarinic Acid and Carvacrol Counteract Aluminium-Induced Oxidative Stress.

Aluminum accumulation, glutathione (GSH) and malondialdehyde (MDA) concentrations as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in erythrocytes and brain and liver homogenates of BALB/c mice treated with Al3+ (7.5 mg/kg/day (0.15 LD50) as AlCl3 (37.08 mg/kg/day), whereas HCl (30.41 mg/kg/day) was used as Cl- control, the treatments were performed for 21 days, i.p., in the presence and absence of rosmarinic acid (0.2805 mg/kg/day (0.05 LD50), 21 days, i.g.) or carvacrol (0.0405 mg/kg/day (0.05 LD50), 21 days, i.g.). The treatment with AlCl3 increased GSH concentration in erythrocytes only slightly and had no effect on brain and liver homogenates. Rosmarinic acid and carvacrol strongly increased GSH concentration in erythrocytes but decreased it in brain and liver homogenates. However, AlCl3 treatment led to Al accumulation in mice blood, brain, and liver and induced oxidative stress, assessed based on MDA concentration in the brain and liver. Both rosmarinic acid and carvacrol were able to counteract the negative Al effect by decreasing its accumulation and protecting tissues from lipid peroxidation. AlCl3 treatment increased CAT activity in mice brain and liver homogenates, whereas the administration of either rosmarinic acid or carvacrol alone or in combination with AlCl3 had no significant effect on CAT activity. SOD activity remained unchanged after all the treatments in our study. We propose that natural herbal phenolic compounds rosmarinic acid and carvacrol could be used to protect brain and liver against aluminum induced oxidative stress leading to lipid peroxidation.

Psyllium (Plantago Ovata Forsk) Husk Powder as a Natural Superdisintegrant for Orodispersible Formulations: A Study on Meloxicam Tablets.

(1) Background: In this work, we investigated the application of a natural superdisintegrant, psyllium (Plantago ovata Forsk) husk powder, for the manufacture of orodispersible meloxicam tablets. Meloxicam was chosen as a model compound for the study. (2) Methods: The tablets were prepared using different concentrations of psyllium husk by direct compression. Bulk density, tapped density, hardness, friability, in vitro disintegration, and dissolution time tests were used to assess the quality of the formulations. (3) Results: Psyllium husk powder significantly increased the dissolution rate of meloxicam. The formulation containing 16 mg of psyllium husk powder showed the lowest wetting time, the highest water absorption ratio, and the lowest disintegration time compared to the control and to the other formulations. These effects may be attributed to the rapid uptake of water due to the vigorous swelling ability of psyllium husk powder. (4) Conclusions: The powder could be recommended as an effective natural superdisintegrant for orodispersible formulations.

GC-MS Analysis of the Composition of the Extracts and Essential Oil from Myristica fragrans Seeds Using Magnesium Aluminometasilicate as Excipient.

Myristica fragrans (f. Myristicaceae) seeds are better known as a spice, but their chemical compounds may have a pharmacological effect. The yield of their composition of extracts and essential oils differs due to different methodologies. The aim of this study was to evaluate an excipient material-magnesium aluminometasilicate-and to determine its influence on the qualitative composition of nutmeg extracts and essential oils. Furthermore, we wanted to compare the yield of essential oil. The extracts were prepared by maceration (M) and ultrasound bath-assisted extraction (UAE), and the essential oil-by hydrodistillation (HD). Conventional methods (UAE, HD) were modified with magnesium aluminometasilicate. The samples were analyzed by gas chromatography-mass spectrometry (GC-MS) method. From 16 to 19 chemical compounds were obtained using UAE with magnesium aluminometasilicate, while only 8 to 13 compounds were obtained using UAE without an excipient. Using our conditions and plant material, for the first time eight new chemical compounds in nutmeg essential oil were identified. Two of these compounds (γ-amorphene and cis-α-bergamotene) were obtained with the use of excipient, the other six (ß-copaene, bergamotene, citronellyl decanoate, cubebol, cubenene, orthodene) by conventional hydrodistillation. Magnesium aluminometasilicate significantly increased the quantity of sabinene (from 6.53% to 61.42%) and limonene (from 0% to 5.62%) in essential oil. The yield of the essential oil from nutmeg seeds was significantly higher using magnesium aluminometasilicate; it increased from 5.25 ± 0.04% to 10.43 ± 0.09%.

The development of Eudragit® NM-based controlled-release matrix tablets.

UNLABELLED: Eudragit® NM was investigated as a matrix former in combination with microcrystalline cellulose as an insoluble filler for preparing controlled-release tablets containing model drugs with different solubility. MATERIAL AND METHODS: Three sets of matrix tablets differing in the drug-to-filler ratio (1:1, 2:1, and 4:1) and polymer amount with diltiazem hydrochloride (freely soluble) or caffeine (sparingly soluble) were prepared. Samples were evaluated by the dissolution test at pH 6.8 corresponding to the upper part of the small intestine; the selected samples were tested at a changing pH level to better simulate in vivo conditions. RESULTS: The prepared matrix tablets fulfilled all the requirements of the European Pharmacopoeia. Tablets with Eudragit® NM showed excellent mechanical characteristics. In vitro studies showed that the set 1:1 was the most suitable for the sustained release of a freely soluble drug concerning the burst effect and the total drug amount released within 12 hours. The significant effect of the drug-to-filler ratio and polymer amount on the dissolution profile was confirmed by similarity factor analysis. A faster drug release was observed during the dissolution test within changing pH levels because of the pH-dependent solubility of diltiazem. A prolonged release of the sparingly soluble drug was not achieved, and a trend for fast disintegration was observed. CONCLUSIONS: The combination of Eudragit®NM with microcrystalline cellulose as an insoluble filler seems to be suitable only for freely soluble drugs, when the amount of the drug and the filler is similar.

Comparison of long-term stability of parenteral all-in-one admixtures containing new lipid emulsions prepared under hospital pharmacy conditions.

UNLABELLED: All-in-one (AIO) admixtures for parenteral nutrition are common in hospital pharmacy practices. They are extemporaneously prepared and should be stable during preparation, storage, and administration. Lipid emulsion is a clinically important and very susceptible component of instability. The objective of study was to evaluate the long-term stability of AIO admixtures containing modern lipid emulsions. MATERIAL AND METHODS: AIO admixtures with two different emulsions (SMOFlipid and Lipoplus) containing the same amount of glucose and complex amino acid solution, and variable amounts of ions were prepared. Samples were evaluated at 2, 5, 8 and 30 days after preparation. The main indicator of AIO system stability was the amount of lipid globules greater than 5 µm in diameter, which is limited by pharmacopoeia. Optical microscopy was used for particle size measurement. RESULTS: All prepared AIO admixtures remained stable during observation. The counts of overlimit lipid particles were within pharmacopeial limit nevertheless tended to increase in time. After 30-day storage, their value was influenced mainly by concentration of calcium ions, which at lower concentrations had a greater impact on SMOFlipid-based admixtures, whereas at the highest concentration on Lipoplus-based admixtures. The concentration of ions and osmolarity remained without changes; pH of admixtures slightly decreased. CONCLUSIONS: Both lipid emulsions were found to be suitable for preparation AIO admixtures with different concentrations of electrolytes. The formulations were stable even if contained high concentrations of divalent ions. The comparison of emulsions revealed the superiority of Lipoplus - electrolyte concentrations and duration of storage had a greater impact on admixtures with SMOFlipid.

The evaluation of formulations for the preparation of new formula pellets.

The aim of the study was to prepare pellets of maidenhair tree (Ginkgo biloba), motherwort (Leonurus cardiaca) and hawthorn (Crataegus monogyna) dry extracts by extrusion/spheronization method. The critical step of this process was the amount of added wetting liquid (water-ethanolic mixture) and the amount of extract in the formulation. The samples of pellets containing 30-50% of extracts were formulated: Pellets contained extracts of Ginkgo, Crataegi and Leonuri. The last sample was aimed at the formulation of pellets with the content of 30% of the mixture of Ginkgo, Leonuri and Crataegi extracts in a ratio of 1:5:6. The remainder of the solid compounds in all formulations was microcrystalline cellulose (Avicel® PH-101). It was not possible to find a way to adequately wet the formulations with the content of extracts higher than 30% because of the unsuitable properties of all three extracts used. On the basis of the experiments, pellets with mixtures of all three previously used extracts were prepared. These pellets showed perfect physico-mechanical properties: Hardness (10.00 ± 2.24 N), friability (0.06%), repose angle (20.99 ± 0.41°), flowability (6.97 ± 0.29 s/100g of pellets), sphericity (0.81 ± 0.05), compressibility index (4.65%), intraparticular porosity (0.09%) and interparticular porosity (45.11%), which predetermine them to other testing and usage (feeling into capsules, tableting, coating etc.).

[Muscle crush injury and crush syndrome]. / Raumenu sutraiskymas ir sutraiskymo sindromas.

Crush injury is defined as compression of extremities or other parts of the body that causes muscle breakdown (traumatic rhabdomyolysis). Systemic consequences of crush injuries are as follows: rhabdomyolysis, electrolyte and acid-base abnormalities, hypovolemia, and acute renal failure. Crush injuries are important injuries in disaster situations: earthquakes, hurricanes, mining and road traffic accidents, war, collapse of buildings, etc. In this review article, there are discussed about epidemiology of crush syndrome, risk factors, pathophysiology (mechanisms of muscle cell injury, release of substances from injured muscles, other consequences of reperfusion), clinical features, differential diagnosis, investigations, complications (acute renal failure, hypovolemic shock, hyperkalemia, infection, compartment syndrome), approach to treatment (adequate rehydration, a forced mannitol-alkaline diuresis, intravenous fluids, management of hyperkalemia, wound care, hyperbaric oxygen, etc.), prognosis, the mortality rate and prevention (timely support may reduce morbidity and mortality).

Anaphylaxis of small arteries: putative role of nitric oxide and prostanoids.

This study investigated possible implication of nitric oxide and prostanoids in anaphylactic reaction in small mesenteric and coronary arteries. MATERIAL AND METHODS. Isolated arteries from guinea pigs, sensitized with 0.5 mL of horse serum or sham-sensitized, were challenged with 1% of horse serum in vitro. Contractile responses of arteries (normalized diameter, 350-450 microm) were recorded by a small blood vessel wire myograph. For inhibition of the release of NO or prostanoids, vessels were pretreated with N(G)-nitro-L-arginine methyl ester (30 microM) or indomethacin (10 microM), respectively. RESULTS. Antigen challenge was followed by contraction of both coronary and mesenteric vessels. Two patterns of contraction were observed: 1) peak contraction - an immediate transient contraction of relatively high amplitude; this was the most common pattern; 2) biphasic: the initial peak contraction was followed by a slow growing contraction with low amplitude. Biphasic pattern was observed in 60% of the mesenteric vessels and 40% of the coronary vessels. Inhibition of NO synthase significantly increased the peak contraction in the coronary vessels and the second-phase contraction in the mesenteric vessels. Inhibition of cyclooxygenase caused a decrease in the peak and second-phase contraction of both the coronary and mesenteric vessels. CONCLUSIONS. Despite anaphylactic contraction, nitric oxide seems to be released from the endothelium following antigen challenge in the small coronary and mesenteric arteries. This may contribute to the development of hypotension during anaphylaxis. Prostanoids are playing a different role - the contracting products of cyclooxygenase pathway are important for the development of anaphylactic contraction of the small isolated arteries.

Effect of anoxia and Polyscias filicifolia Bailey biomass tincture on the activity of tRNA and aminoacyl-tRNA synthetases in isolated pig heart.

OBJECTIVE: The aim of this study was to investigate effect of anoxia and Polyscias filicifolia Bailey biomass tincture on the activities of different tRNA and aminoacyl-tRNA synthetases in isolated pig heart. MATERIAL AND METHODS: The isolated pig heart was perfused according to the modified method of Langendorf, using an artificial blood circulation apparatus. Anoxia 20 min in duration was performed by perfusion of isolated heart with Krebs-Henseleit bicarbonate buffer saturated with gas mixture (95% N(2) and 5% CO(2)). Control heart was perfused with the same buffer saturated with gas mixture (95% O(2) and 5% CO(2)). Effect of Polyscias filicifolia Bailey biomass tincture was evaluated by perfusion of isolated heart with a buffer containing tincture. Total tRNA and aminoacyl-tRNA synthetases were isolated from pig heart. Activities of tRNA and aminoacyl-tRNA synthetases were measured by the aminoacylation reaction using C(14)-amino acids. RESULTS: Anoxia 20 min in duration has caused a decrease in the acceptor activity of tRNA and increase in the activities of aminacyl-tRNA synthetases. Polyscias filicifolia Bailey tincture did not affect the acceptor activity of tRNA and activities aminacyl-tRNA synthetases. After 20-min anoxic perfusion with the buffer containing Polyscias filicifolia Bailey biomass tincture, the acceptor activities of tRNA increased to the control value and activities of aminacyl-tRNA synthetases reached the control value. CONCLUSIONS: The acceptor activity of tRNA from isolated pig heart decreased and activities of aminacyl-tRNA synthetases increased under anoxia. Perfusion with buffer containing tincture of Polyscias filicifolia Bailey biomass restored acceptor activities of tRNA and activities of aminacyl-tRNA synthetases.

[Methadone treatment and its dangers]. / Metadonas ir gydymo juo pavojai.

Methadone is a long-acting synthetic opioid with high affinity for various opioid receptors, especially for m-opioid receptors. Methadone has been used as a successful pharmacologic intervention for the treatment of heroin dependence and acute and chronic pain. This treatment is effective for opiate addiction, reducing morbidity and mortality associated with heroin use. However, overdosing with methadone has become a growing phenomenon because of the increased availability of this drug. Patients enrolled in a methadone maintenance treatment program may become physically dependent and may experience methadone withdrawal symptoms. In this review article, there are discussed about pharmacokinetic and pharmacodynamic properties of methadone, clinical symptoms of its overdose, dosage problems, detection of methadone in biological samples, treatment, and causes of methadone overdose-related deaths.

Nutritional habits of middle-aged schoolchildren from Kaunas town and Raseiniai district.

OBJECTIVE: To evaluate nutritional habits of middle-aged schoolchildren living in a town and district of Lithuania. MATERIAL AND METHODS: The 8th-9th-grade schoolchildren were questioned by an anonymous questionnaire. A total of 329 students, 169 from Kaunas and 160 from Raseiniai district, participated in the study. RESULTS: Only half of students reported that they had breakfast (61.3% of schoolboys and 47.6% of schoolgirls). More students from the district had dinner in the school canteen as compared to Kaunas students. Only 14.0% of schoolchildren followed nutrition regimen (14.8% of students from Kaunas and 13.1% of students from Raseiniai always had their meal at the same time). Every second schoolboy and schoolgirl consumed vegetables and fruits every day. Whole grain bread was consumed every day similarly frequently by students from Kaunas and Raseiniai, 25.4% and 18.8%, respectively; the students from Kaunas consumed skim milk more frequently, 26.0% and 11.9%, respectively (P<0.05). Confectionery was consumed more frequently by schoolchildren from Kaunas as compared to schoolchildren from Raseiniai district (63.9% vs. 55.0%); however, it was consumed more frequently by boys than girls. Less than one-fourth of Kaunas students (20.7%) consumed potato chips every day, whereas the percentage of the students from Raseiniai district was only 10.0% (P<0.05). Pizzas, kebabs, and hamburgers were consumed more frequently by schoolboys than schoolgirls. Knowledge of healthy nutrition was obtained mainly from media by 48.6% of students; every eighth student got this information from parents, every tenth from physicians, and 7.0% from teachers. CONCLUSIONS: Middle-aged students from both Kaunas town and Raseiniai district did not follow nutrition regimen; half of them did not have their breakfast before going to school. Fruits and vegetables as recommended foods were consumed by half of the participants; every fourth student consumed skim milk, and every fifth student consumed whole grain bread. The students more frequently consumed such foods as confectionery and smoked meat, which are not recommended (every second student); every fourth had an intake of carbonated drinks (the students from Kaunas more frequently) and potato chips (the students from Kaunas more frequently), and every tenth consumed pizzas and fried potatoes. More than half of students obtained knowledge of healthy nutrition from media, and every tenth--from the physicians.

[Use of recombinant activated factor VII]. / Rekombinantinio aktyvinto VII kresejimo faktoriaus vartojimas.

Recombinant activated factor VII (rFVIIa) has been used in the treatment of various congenital and acquired hemostatic disorders for more than 10 years. Hemostasis is initiated by the FVIIa bound to tissue factor (TF), which constitutes only approximately 1% of total amount of the FVII protein existing in the blood. rFVII becomes activated only after the binding to the TF, released at the site of tissue injury. The efficiency of rFVIIa in the treatment of such life-threatening hemorrhagic states like hemophilia reaches up to 76-84%. rFVIIa is successfully used in the treatment of congenital deficiency of factor VII. It normalizes prothrombin time in the patients with the liver diseases and in cases of overdose of indirect anticoagulants. It is also useful for patients suffering from thrombocytopenia, thrombocyte function disorders, hemophilia A and B with development of inhibitors. rFVIIa allows overcoming uncontrollable hemorrhages, etc. It is supposed that rFVIIa is becoming a universal hemostatic drug.

Inotropic and lusitropic effects of Perilla frutescens (L.) Britton extract on the rabbit myocardium.

BACKGROUND: Common perilla (Perilla frutescens (L.) Britton) is a plant cultivated in many countries around the world. Although its immunomodulating and antioxidative properties are well known, there is a lack of data about the cardiotropic activity of the plant. The objective of this study was to determine the influence of Perilla frutescens extract on the myocardial contractility in vitro and as a food supplement in vivo. MATERIAL AND METHODS: Rabbits of the experimental group were fed with a supplement of 100 mg/kg of Perilla frutescens extract for 14 days. Rabbits of control group were fed with ordinary food. The maximal mechanical activity of isolated myocardial preparations, obtained from the rabbits of both groups, was tested during the perfusion with Ringer's solution containing 5 microM of adrenaline and 4.5 mM of CaCl2. For the assessment of the direct influence of Perilla frutescens extract on the myocardial contractility in vitro isolated heart preparations were perfused with 0.01, 0.1, and 1.0 mg/ml of Perilla frutescens extract. RESULTS: The maximum force of isometric contraction, maximum velocity of force development, and maximum velocity of relaxation were higher among the atrial and ventricular preparations from the experimental group, as compared with the control group. Perfusion of the myocardial preparations with different concentrations of Perilla frutescens extract revealed slight dose-dependent increase in the parameters of contraction and relaxation. CONCLUSIONS: The consumption of Perilla frutescens extract as a food supplement leads to an increase in the contractility of the rabbit myocardium. Perilla frutescens extract in vitro had a dose-dependent positive inotropic and lusitropic effect on the rabbit myocardium.

[Acute salicylate poisoning]. / Apsinuodijimas salicilatais.

Although aspirin (acetylsalicylic acid) has become widely available without prescription, cases of self-poisoning due to overdose of salicylates are quite uncommon, with a low reported mortality. However, severe poisoning with these preparations is life threatening. Besides the aspirin, there are other sources of salicylate poisoning, such as an excessive application of topical agents, ingestion of salicylate containing ointments, use of keratolytic agents or agents containing methyl salicylate (e.g. oil of wintergreen). Most of these preparations are liquid, highly concentrated and lipid soluble, and, therefore, they are able to provoke a severe, rapid salicylate poisoning. On the basis of clinical and metabolic features or salicylate concentration in plasma it is very important to diagnose severe poisoning with salicylates in time and prescribe an adequate treatment. In the present review article various aspects of salicylate poisoning and its treatment are discussed: epidemiology, pharmacokinetics and pharmacodynamics of salicylates, clinical manifestations of their toxicity, management, enhanced elimination and prognosis.

[Hallucinogenic mushrooms]. / Haliucinogeniniai grybai.

The group of hallucinogenic mushrooms (species of the genera Conocybe, Gymnopilus, Panaeolus, Pluteus, Psilocybe, and Stropharia) is psilocybin-containing mushrooms. These "magic", psychoactive fungi have the serotonergic hallucinogen psilocybin. Toxicity of these mushrooms is substantial because of the popularity of hallucinogens. Psilocybin and its active metabolite psilocin are similar to lysergic acid diethylamide. These hallucinogens affect the central nervous system rapidly (within 0.5-1 hour after ingestion), producing ataxia, hyperkinesis, and hallucinations. In this review article there are discussed about history of use of hallucinogenic mushrooms and epidemiology; pharmacology, pharmacodynamics, somatic effects and pharmacokinetics of psilocybin, the clinical effects of psilocybin and psilocin, signs and symptoms of ingestion of hallucinogenic mushrooms, treatment and prognosis.