Off-label use of drugs is widely known as unapproved use of approved drugs, and it can be perceived as a relatively simple concept. Even though it has been in existence for many years, prescribing and dispensing of drugs in an off-label regimen is still a current issue, triggered especially by unmet clinical needs. Several therapeutic areas require off-label approaches; therefore, this practice is challenging for prescribing physicians. Meanwhile, the regulatory agencies are making efforts in order to ensure a safe practice. The present paper defines the off-label concept, and it describes its regulation, together with several complex aspects associated with clinical practices regarding rare diseases, oncology, pediatrics, psychiatry therapeutic areas, and the safety issues that arise. A systematic research of the literature was performed, using terms, such as “off-label”, ”prevalence”, ”rare diseases”, ”oncology”, ”psychiatry”, ”pediatrics”, and ”drug repurposing”. There are several reasons for which off-label practice remains indispensable in the present; therefore, efforts are made worldwide, by the regulatory agencies and governmental bodies, to raise awareness and to ensure safe practice, while also encouraging further research.

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.

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.

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.

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.