Assessing ß-Sitosterol Levels in Dietary Supplements for Benign Prostatic Hyperplasia: Implications for Therapeutic Efficacy.

Introduction Benign prostatic hyperplasia (BPH) is a prevalent condition among aging men that affects their life quality due to urinary symptoms. Current pharmacologic treatments, often lead to sexual dysfunction, so dietary supplements (DS) containing plant-based compounds such as ß-sitosterol (SIT) are preferred. DS are highly accessible and widely used, but poorly regulated, so often patients are victims of fraud. The use of DS to treat BPH symptoms is questionable, and this may be due not to the efficacity of the active compound but to the quality of commonly available DS. Aim This study aimed to assess the concentration of SIT in DS available on the market and evaluate whether the concentration of the active compound at the recommended dosage is sufficient to elicit beneficial effects in BPH. Method An HPLC-UV method based on direct saponification and acid hydrolysis was developed for the quantification of free and conjugated SIT in DS. The concentration of SIT in various DS was determined and compared with the one declared on the label. Results The chromatographic analysis confirmed the presence of SIT in all the DS but also showed a considerable variability of SIT content among DS, with only one product meeting the necessary concentration to bring potential benefits in BPH. Conclusion The study highlights inconsistencies in SIT content among DS and the importance of DS containing a standardized extract of SIT. Quality control measures are imperative to ensure that consumers receive effective and safe SIT-based DS to manage BPH symptoms. Further research is needed to establish standardized dosages and to evaluate their long-term efficacy and safety.

Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review.

Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and the World Anti-Doping Agency (WADA) has classified TMZ on the S4 list of prohibited substances since 2014. The purpose of this narrative mini-review is to emphasize the biochemical aspects underlying the abusive use of TMZ among athletes as a metabolic modulator of cardiac energy metabolism. The myocardium's ability to adapt its energy substrate utilization between glucose and fatty acids is crucial for maintaining cardiac function under various conditions, such as rest, moderate exercise, and intense effort. TMZ acts as a partial inhibitor of fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase (KAT), shifting energy production from long-chain fatty acids to glucose, reducing oxygen consumption, improving cardiac function, and enhancing exercise capacity. Furthermore, TMZ modulates pyruvate dehydrogenase (PDH) activity, promoting glucose oxidation while lowering lactate production, and ultimately stabilizing myocardial function. TMZs role in reducing oxidative stress is notable, as it activates antioxidant enzymes like glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). In conclusion, TMZs biochemical mechanisms make it an attractive but controversial option for athletes seeking a competitive edge.

Fennel Essential Oil as a Complementary Therapy in the Management of Diabetes.

Diabetes is a serious pathology that affects a significant number of people worldwide. Its progression is rapid and leads to serious complications if glycemic control is missing. The micro and macrovascular complications of diabetes produce disabilities over time that affect the daily lives of patients. The major challenge of diabetes therapy is to reach a stable glycemic state and to delay the onset of specific complications. Aromatherapy is considered an alternative or complementary therapy, but in recent years, there has been a tendency to overuse essential oils. The present study was designed to evaluate and compare the effects produced by the topical and oral administration of fennel essential oil to diabetic rats. Eighteen compounds in fennel essential oil were identified by gas chromatography-mass spectrometry (GC-MS) analysis. The major compounds were trans-anethole (64.6%) and fenchone (24.5%). The in vivo study revealed that after a four-week treatment with fennel essential oil, the rats' glycemic levels were significantly reduced (p ≤ 0.05). Furthermore, there were no differences between the two routes of administration. In addition, an ex vivo study underlined the potential effect of this essential oil in the prevention of cataract formation.

LC-MS/MS assisted biomonitoring of ropivacaine and 3-OH-ropivacaine after plane block anesthesia for cardiac device implantation.

Introduction: Ropivacaine is a popular local anesthetic used for regional anesthesia or for pain management. Although designed as an enantiomerically pure drug, an aspect that reduces the adverse effects, its toxicological effects are still a risk. As such, biomonitoring to assure appropriate dosage and bioavailability are essential to avoid complications during or post-surgery. Methods: The study focused on developing a sensitive, selective, and accurate liquid chromatography-mass spectrometry (LCMS/MS) method which facilitates the biomonitoring of ropivacaine and its main metabolite in plasma after regional anesthesia using ropivacaine. Results and Discussion: The method was validated with regards to all relevant parameters, such as sensitivity, selectivity, accuracy, precision, and the effect of sample matrix. The method was successfully used in a pilot study, which included one patient undergoing plane block anesthesia for cardiac device implantation. The results showed the method is appropriate for its intended purpose and could even be used in other, similar applications.

Potential Defence Mechanisms Triggered by Monosodium Glutamate Sub-Chronic Consumption in Two-Year-Old Wistar Rats.

Monosodium glutamate (MSG) is the sodium salt of glutamic acid (GLA), used as a flavour enhancer. MSG is considered a controversial substance. It is incriminated in disturbing the antioxidant system, but also has beneficial effects, as GLA metabolism plays a crucial role in homeostasis. This study highlights which positive or negative aspects of MSG sub-chronic consumption are better reflected in subjects potentially affected by advanced age. Daily doses of MSG were administered to four groups of two-year-old Wistar rats for 90 days: (I) 185 mg/kg bw, (II) 1500 mg/kg bw, (III) 3000 mg/kg bw and (IV) 6000 mg/kg bw, compared to a MSG non-consumer group. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct and total bilirubin, total cholesterol, triglycerides, creatinine and urea levels were analysed; stomach, liver and kidney samples were subjected to histopathological analysis. Although, in most cases, there were no statistical differences, interesting aspects of the dose-effect relationship were observed. After MSG sub-chronic consumption, the positive aspects of GLA seem to be reflected better than the negative ones. The hormesis effect, with low-level reactive oxygen species' protective effects and GLA metabolism, may represent the hypothesis of a potential defence mechanism triggered by MSG sub-chronic consumption in ageing rats.

Benzydamine-An Affordable Over-the-Counter Drug with Psychoactive Properties-From Chemical Structure to Possible Pharmacological Properties.

Benzydamine is a non-steroidal anti-inflammatory drug with distinct pharmacological properties from other compounds in the same therapeutic class. The differences are structural and pharmacological in nature; the anti-inflammatory mechanism is not strictly explained by the ability to interfere with the synthesis of prostaglandins. The compound is used strictly in local inflammatory diseases (inflammation in the oral and vaginal mucosa). In addition to the therapeutic indications found in the summary of product characteristics (SPC), the compound is used, in high doses, as a psychotropic substance for oral administration, having similar properties to lysergic acid diethylamide (LSD). As an over-the-counter (OTC) compound, it is easy to obtain, and the consequences of using it for purposes other than those assumed by the manufacturer raise various concerns. The reasons are related to the pharmacodynamic and pharmaco-toxicological properties, since neither the mechanism of action nor the possible side effects that would result from systemic consumption, in high doses, even occasionally, have been fully elucidated. The present review aims to analyze the pharmacodynamic properties of benzydamine, starting from the chemical structure, by comparison with structurally similar compounds registered in therapy (as an anti-inflammatory or analgesic) or used for recreational purposes.

The Lack of Standardization and Pharmacological Effect Limits the Potential Clinical Usefulness of Phytosterols in Benign Prostatic Hyperplasia.

The prevalence of benign prostatic hyperplasia (BPH) markedly increases with age. Phytotherapeutic approaches have been developed over time owing to the adverse side effects of conventional medications such as 5-reductase inhibitors and α1-adrenergic receptor antagonists. Therefore, dietary supplements (DS) containing active compounds that benefit BPH are widely available. Phytosterols (PSs) are well recognized for their role in maintaining blood cholesterol levels; however, their potential in BPH treatment remains unexplored. This review aims to provide a general overview of the available data regarding the clinical evidence and a good understanding of the detailed pharmacological roles of PSs-induced activities at a molecular level in BPH. Furthermore, we will explore the authenticity of PSs content in DS used by patients with BPH compared to the current legislation and appropriate analytical methods for tracking DS containing PSs. The results showed that PSs might be a useful pharmacological treatment option for men with mild to moderate BPH, but the lack of standardized extracts linked with the regulation of DS containing PSs and experimental evidence to elucidate the mechanisms of action limit the use of PSs in BPH. Moreover, the results suggest multiple research directions in this field.

Cannabidiol: Bridge between Antioxidant Effect, Cellular Protection, and Cognitive and Physical Performance.

The literature provides scientific evidence for the beneficial effects of cannabidiol (CBD), and these effects extend beyond epilepsy treatment (e.g., Lennox-Gastaut and Dravet syndromes), notably the influence on oxidative status, neurodegeneration, cellular protection, cognitive function, and physical performance. However, products containing CBD are not allowed to be marketed everywhere in the world, which may ultimately have a negative effect on health as a result of the uncontrolled CBD market. After the isolation of CBD follows the discovery of CB1 and CB2 receptors and the main enzymatic components (diacylglycerol lipase (DAG lipase), monoacyl glycerol lipase (MAGL), fatty acid amino hydrolase (FAAH)). At the same time, the antioxidant potential of CBD is due not only to the molecular structure but also to the fact that this compound increases the expression of the main endogenous antioxidant systems, superoxide dismutase (SOD), and glutathione peroxidase (GPx), through the nuclear complex erythroid 2-related factor (Nrf2)/Keep1. Regarding the role in the control of inflammation, this function is exercised by inhibiting (nuclear factor kappa B) NF-κB, and also the genes that encode the expression of molecules with a pro-inflammatory role (cytokines and metalloproteinases). The other effects of CBD on cognitive function and physical performance should not be excluded. In conclusion, the CBD market needs to be regulated more thoroughly, given the previously listed properties, with the mention that the safety profile is a very good one.

Caffeine and Its Antioxidant Properties-It Is All about Dose and Source.

Caffeine is the most frequently used substance with a central nervous system stimulant effect, but its consumption is most often due to the intake of foods and drinks that contain it (coffee, tea, chocolate, food supplements with plant extracts of Guarana, Mate herba, Cola nuts). Due to its innocuity, caffeine is a safe xanthine alkaloid for human consumption in a wide range of doses, being used for its central nervous stimulating effect, lipolytic and diuresis-enhancing properties, but also as a permitted ergogenic compound in athletes. In addition to the mechanisms that explain the effects of caffeine on the targeted organ, there are many proposed mechanisms by which this substance would have antioxidant effects. As such, its consumption prevents the occurrence/progression of certain neurodegenerative diseases as well as other medical conditions associated with increased levels of reactive oxygen or nitrogen species. However, most studies that have assessed the beneficial effects of caffeine have used pure caffeine. The question, therefore, arises whether the daily intake of caffeine from food or drink has similar benefits, considering that in foods or drinks with a high caffeine content, there are other substances that could interfere with this action, either by potentiating or decreasing its antioxidant capacity. Natural sources of caffeine often combine plant polyphenols (phenol-carboxylic acids, catechins) with known antioxidant effects; however, stimulant drinks and dietary supplements often contain sugars or artificial sweeteners that can significantly reduce the effects of caffeine on oxidative stress. The objective of this review is to clarify the effects of caffeine in modulating oxidative stress and assess these benefits, considering the source and the dose administered.

Positive Aspects of Oxidative Stress at Different Levels of the Human Body: A Review.

Oxidative stress is the subject of numerous studies, most of them focusing on the negative effects exerted at both molecular and cellular levels, ignoring the possible benefits of free radicals. More and more people admit to having heard of the term "oxidative stress", but few of them understand the meaning of it. We summarized and analyzed the published literature data in order to emphasize the importance and adaptation mechanisms of basal oxidative stress. This review aims to provide an overview of the mechanisms underlying the positive effects of oxidative stress, highlighting these effects, as well as the risks for the population consuming higher doses than the recommended daily intake of antioxidants. The biological dose-response curve in oxidative stress is unpredictable as reactive species are clearly responsible for cellular degradation, whereas antioxidant therapies can alleviate senescence by maintaining redox balance; nevertheless, excessive doses of the latter can modify the redox balance of the cell, leading to a negative outcome. It can be stated that the presence of oxidative status or oxidative stress is a physiological condition with well-defined roles, yet these have been insufficiently researched and explored. The involvement of reactive oxygen species in the pathophysiology of some associated diseases is well-known and the involvement of antioxidant therapies in the processes of senescence, apoptosis, autophagy, and the maintenance of cellular homeostasis cannot be denied. All data in this review support the idea that oxidative stress is an undesirable phenomenon in high and long-term concentrations, but regular exposure is consistent with the hormetic theory.

An Updated Systematic Review of Vaccinium myrtillus Leaves: Phytochemistry and Pharmacology.

Bilberry leaves are used in many countries in traditional medicine for treating a wide variety of diseases. Due to the high therapeutic potential of Vaccinium myrtillus (VM) leaves, this review aims to present the latest knowledge on the phytochemical profile, as well as the therapeutic effects of this herbal drug. The review was conducted according to the Prisma guidelines, and the scientific databases were searched using combinations of the following keywords: "Vaccinium myrtillus", "leaves", "bilberry". Recent research was focused on the influence of abiotic factors on the phytochemical composition, and it seems that there are significant differences between the herbal drugs collected from different countries. The phytochemical composition is correlated with the broad spectrum of pharmacological effects. The paper outlines the potent antimicrobial activity of VM extracts against multidrug-resistant bacterial strains, and also the pathways that are modulated by the unique "cocktail" of phytoconstituents in different metabolic alterations. Reviewing the research articles published in the last 10 years, it seems that bilberry leaves have been slightly forgotten, although their phytochemical and pharmacological characteristics are unique.

Profiling the Concentration of Reduced and Oxidized Glutathione in Rat Brain Using HPLC/DAD Chromatographic System.

This study aimed to develop a HPLC/DAD method in order to determine and quantify the reduced glutathione (GSH) and oxidized glutathione (GSSG) levels in rat brain. Due to the presence of the thiol group (-SH), GSH can interact with the Ellman's reagent (DTNB), with which it forms a reaction product through which the level of GSH can be quantified, using the DAD detection system. Chromatographic separation was achieved after a derivatization process by using a mobile phase acetonitrile (A) and phosphate buffer (20 mM, pH = 2.5) (B). The compounds of interest were detected at 330 nm using a chromatographic C8 column. The method of determination met the validation criteria, specified by the regulatory bodies. The applicability of the method was demonstrated in a chronic toxicology study of central nervous system (CNS), following different treatment regimens with haloperidol.

A Simple HPLC/DAD Method Validation for the Quantification of Malondialdehyde in Rodent's Brain.

In the present study, a HPLC/DAD method was set up to allow for the determination and quantification of malondialdehyde (MDA) in the brain of rodents (rats). Chromatographic separation was achieved on Supelcosil LC-18 (3 µm) SUPELCO Column 3.3 cm × 4.6 mm and Supelco Column Saver 0.5 µm filter by using a mobile phase acetonitrile (A) and phosphate buffer (20 mM, pH = 6) (B). Isocratic elution was 14% for (A) and 86% for (B). The injection volume (loop mode) was 100 µL with an analysis time of 1.5 min. Flow rate was set at 1 mL/min. The eluted compound was detected at 532 nm by a DAD detector by keeping the column oven at room temperature. The results indicated that the method has good linearity in the range of 0.2-20 µg/g. Both intra- and inter-day precision, expressed as RSD, were ≤15% and the accuracies ranged between ±15%. The lower limit of quantification (LLOQ), stability, and robustness were evaluated and satisfied the validation criteria. The method was successfully applied in a study of chronic toxicology following different treatment regimens with haloperidol and metformin.

Glutamate - A multifaceted molecule: Endogenous neurotransmitter, controversial food additive, design compound for anti-cancer drugs. A critical appraisal.

One of the most widely used flavour enhancers in the food industry is monosodium glutamate (MSG). MSG consumption has been on an upward trend, worrying in terms of potential toxic effects. This review is focused on the long-term toxicity of MSG and the experimental evidence that supports it. The article's primary purpose was to survey recently published data regarding the consumption of MSG within safe limits. The administered doses in animal models are very varied and have given rise to controversy. Also, the paper comprises pathways to lower MSG toxicity and highlight other underexploited biological effects, as anti-cancer potential. The administration of MSG, combined with various compounds, has been shown benefit against toxic effects. Several recent studies have identified a possible mechanism that recommends MSG and some derivatives as potential anti-cancer agents. New anti-cancer compounds based on the glutamic acid structure must be studied and further exploited. International regulations require harmonization of safe doses of MSG based on current scientific studies. Replacing MSG with other umami flavour enhancers may be a safer alternative for human health in the future. The biological consequences of MSG consumption or therapeutical administration have not been fully deciphered yet.

Psychoactive Drugs-From Chemical Structure to Oxidative Stress Related to Dopaminergic Neurotransmission. A Review.

Nowadays, more and more young people want to experience illegal, psychoactive substances, without knowing the risks of exposure. Besides affecting social life, psychoactive substances also have an important effect on consumer health. We summarized and analyzed the published literature data with reference to the mechanism of free radical generation and the link between chemical structure and oxidative stress related to dopaminergic neurotransmission. This review presents data on the physicochemical properties, on the ability to cross the blood brain barrier, the chemical structure activity relationship (SAR), and possible mechanisms by which neuronal injuries occur due to oxidative stress as a result of drug abuse such as "bath salts", amphetamines, or cocaine. The mechanisms of action of ingested compounds or their metabolites involve intermediate steps in which free radicals are generated. The brain is strongly affected by the consumption of such substances, facilitating the induction of neurodegenerative diseases. It can be concluded that neurotoxicity is associated with drug abuse. Dependence and oxidative stress are linked to inhibition of neurogenesis and the onset of neuronal death. Understanding the pathological mechanisms following oxidative attack can be a starting point in the development of new therapeutic targets.

Medical Knowledge, Religious Beliefs, and Free Will: Attitudes and Opinions of Various Undergraduate Female Respondents Regarding Oral Contraception. A Questionnaire-Based Study.

The decision to use oral contraception varies and is based on several considerations: Personal reasons, the evaluation of the benefit/ risk ratio, and religious beliefs. In this research, a questionnaire was distributed to 422 female students from the George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mures, Romania (UMPhST Târgu Mureș, Romania), aged between 19 and 24 years old. The first endpoint of the study was to evaluate the use of hormonal contraception by the sexually active female population. The second endpoint was to assess the degree of awareness of the benefit/risk ratio of oral contraceptive use. The third endpoint was to evaluate the influence of religious beliefs regarding the decision to use this type of pharmaceutical product. Our results show that only a small percentage of students chose to use oral contraceptive pills (OCP). Fortunately, most of the respondents were well-informed and used a particular contraceptive drug based on a healthcare professional's recommendation. Another aspect that emphasizes the choice of contraceptive method is the religious affiliation, which could influence the decision to use OCP. For the students with medical knowledge, the advice of a healthcare professional seems to be quite important, because they are aware of the risks of improper use of OCP. Although religious doctrines affect the decision to use oral contraception, this is not always taken into account, as the use of OCP is a personal decision.

Tribulus terrestris Efficacy and Safety Concerns in Diabetes and Erectile Dysfunction, Assessed in an Experimental Model.

The present project aims to evaluate Tribulus terrestris (TT) extracts by addressing various possible mechanisms of action in order to see whether the use of TT supplements in diabetes and diabetes complications is justified. Diabetic rats were divided into three groups: diabetic control group, TT extract with low protodioscin content group (TT-LPC) and TT extract with high protodioscin content group (TT-HPC). After twelve weeks of treatment, fasting blood glucose, insulin, LH, FSH and testosterone levels were measured. Both TT preparations reduced elevated blood glucose level. Insulin and luteinizing hormone levels were not significantly different compared with the control group; however, the FSH and testosterone levels were significantly higher in the TT-HPC group compared with the diabetic control group. The testosterone level is correlated in part with the protodioscin concentration in extracts and is probably mediated through an FSH-linked pathway.

A Comprehensive Review of the Phytochemical, Pharmacological, and Toxicological Properties of Tribulus terrestris L.

The general spread of Tribulus terrestris L. (South Africa, Australia, Europe, and India), the high content of active ingredients (in particular sterol saponins, as well as flavonoids, tannins, terpenoids, phenol carboxylic acids, and alkaloids), and its frequent uses in folk medicine, and as food supplements highlight the importance of evaluating its phytopharmacological properties. There are miscellaneous hypotheses that the species could have a high potential for the prevention and improvement of various human conditions such as infertility, low sexual desire, diabetes, and inflammatory diseases. Worldwide, numerous herbal supplements are commercialized with indications mostly to improve libido, sexual performance in both sexes, and athletic performance. Phytochemical studies have shown great disparities in the content of active substances (in particular the concentration of furostanol and spirostanol saponoside, considered to be the predominant active ingredients related to the therapeutic action). Thus, studies of experimental pharmacology (in vitro studies and animal models in vivo) and clinical pharmacology (efficacy and safety clinical trials) have sometimes led to divergent results; moreover, the presumed pharmacodynamic mechanisms have yet to be confirmed by molecular biology studies. Given the differences observed in the composition, the plant organ used to obtain the extract, the need for selective extraction methods which are targeted at the class of phytocompounds, and the standardization of T. terrestris extracts is an absolute necessity. This review aims to highlight the phytochemical, pharmacological, and toxicological properties of T. terrestris, with a focus on the contradictory results obtained by the studies conducted worldwide.

With or Without Internal Standard in HPLC Bioanalysis. A Case Study.

The mandatory strategy of using internal standard in HPLC is still controversial. Despite that the introduction of internal standard methodology in the early stage of development of HPLC technology was used to improve method accuracy and precision, there are still practical situations in which a simple external standard quantification is adequate. The aim of the study is to compare the determination of meloxicam (MXC) in human plasma by HPLC with or without using an internal standard according to some key points related to the reason of introducing the internal standardization such as the reducing of sample preparation errors or variability for low injection volumes. The HPLC analysis was performed on reversed phase with UV detection after protein precipitation. Piroxicam (PXC) was used as an internal standard. The two methods are compared in terms of accuracy and precision over the same concentration range. The stability of the analyte has been proved. According to the results, the quantitative determination of MXC in human plasma after simple protein precipitation by using PXC as an internal standard does not bring any significant improvement of accuracy and precision of the experimental measurements.

Vaccinium Extracts as Modulators in Experimental Type 1 Diabetes.

Antihyperglycemic effects of four extracts obtained from leaves and fruits of Vaccinium myrtillus and Vaccinium corymbosum were assessed in diabetic rats. In addition, the effects of extracts on diabetic-related complications such as the development of diabetic cataract and oxidative stress were evaluated. Type 1 diabetes was induced with a single dose of streptozotocin in Wistar rats. The rats were randomly divided into seven equal groups: NC-normal control, DC-diabetic control, PC-positive control treated with metformin, VML-received V. myrtillus leaf extract, VMLF-received VML and fruit extract, VCL-received V. corymbosum leaf extract, and VCLF-received VCL and fruit extract. Body weight and glucose levels were monitored every second week. After 8 weeks of treatment, serum glucose, insulin, and malondialdehyde were measured. Lenses were removed after sacrifice and eight lenses from each group were randomly selected for evaluation of cataract development. A decrease in body weight was observed in all diabetic groups in the first weeks. In the VML group, no significant decrease was observed. Glucose levels during the experiment were high in DC, PC, and VCL groups, with no improvement during the 8 weeks. In VML, VMLF, and VCLF groups, a decrease in blood glucose levels was observed. Similar results regarding serum insulin and glucose levels at the end of the experiment were observed within groups. V. myrtillus extracts prevented the development of cataract compared with the DC group (P < .05).