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(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At the present time, the exploration of novel therapies for alleviating diabetic-neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect the sildenafil (phosphodiesterase-5 inhibitor)–metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats. (2) Methods: This study involved a cohort of 70 diabetic rats and 10 non-diabetic rats. Diabetic neuropathy was induced by a single dose of 130 mg/kg alloxan. The rats were submitted to thermal stimulus test using a hot–cold plate and to tactile stimulus test using von Frey filaments. Moreover, at the end of the experiment, the animals were sacrificed and their brains and livers were collected to investigate the impact of this combination on TNF-α, IL-6, nitrites and thiols levels. (3) Results: The results demonstrated that all sildenafil–metformin combinations decreased the pain sensitivity in the von Frey test, hot plate test and cold plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil–metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect on alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.

Phytocannabinoids, a diverse group of naturally occurring compounds extracted from the Cannabis plant, have attracted interest due to their potential pharmacological effects and medicinal uses. This comprehensive review presents the intricate pharmacological profiles of phytocannabinoids while exploring the diverse impacts these substances have on biological systems. From the more than one hundred cannabinoids which were identified in the Cannabis plant so far, cannabidiol (CBD) and tetrahydrocannabinol (THC) are two of the most extensively studied phytocannabinoids. CBD is a non-psychoactive compound, which exhibits potential anti-inflammatory, neuroprotective, and anxiolytic properties, making it a promising candidate for a wide array of medical conditions. THC, known for its psychoactive effects, possesses analgesic and antiemetic properties, contributing to its therapeutic potential. In addition to THC and CBD, a wide range of additional phytocannabinoids have shown intriguing pharmacological effects, including cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN). The endocannabinoid system, made up of the enzymes involved in the production and breakdown of endocannabinoids, cannabinoid receptors (CB1 and CB2), and endogenous ligands (endocannabinoids), is essential for preserving homeostasis in several physiological processes. Beyond their effects on the endocannabinoid system, phytocannabinoids are studied for their ability to modify ion channels, neurotransmitter receptors, and anti-oxidative pathways. The complex interaction between phytocannabinoids and biological systems offers hope for novel treatment approaches and lays the groundwork for further developments in the field of cannabinoid-based medicine. This review summarizes the state of the field, points out information gaps, and emphasizes the need for more studies to fully realize the therapeutic potential of phytocannabinoids.

Oncological diseases are the most common cause of death worldwide, it is estimated that 25% of the population will face the diagnosis of cancer during life. Phytochemicals such as cannabinoids (CBs) have been used in various branches of medicine for their properties, and the discovery of the anti-tumor, anti-emetic and anti-inflammatory effects of some of these substances has encouraged their use in oncology. Phytocannabinoids, cannabidiol (CBD) and Δ-9-tetra-hydrocannabinol (THC), have numerous anti-emetic, analgesic, orexigenic, anti-inflammatory / immunosuppressive pharmacodynamic effects. In recent years, studies have been aimed at evaluating their efficacy as antineoplastic agents. Much in vivo and in vitro research has demonstrated the efficacy of CBs on certain tumor cell lines, highlighting their potential role in the complementary treatment of cancer. This paper suggests that exploring the molecular mechanisms induced by CBs in cancer cells may contribute to the development of effective treatments in oncological diseases.

Cannabinoids, terpenophenolic chemicals found only in cannabis, are primarily responsible for cannabis pharmacologic effects; nearly 150 distinct cannabinoids have been identified thus far. Among these, the main psychoactive molecule, tetrahydrocannabinol (THC), and the non-psychoactive counterpart, cannabidiol (CBD) are distinguishable. In the past decade, a CBD-containing pharmaceutical preparation was approved by Food and Drug Administration (FDA) for the treatment of drug-resistant epileptic seizures in children, and research trials for a variety of additional medical conditions for which CBD has been suggested as a therapy are being conducted. Additionally, the number of “CBD-containing” dietary supplements, largely available online, is increasing rapidly. Consequently, the necessity for the development of qualitative and quantitative methodologies for the analysis of the bioactive components of Cannabis is rising because of the increase in the production of therapeutic cannabis products. One of the analytical methods with good potential in cannabinoids analysis is capillary electrophoresis (CE). It has advantages related to high separation efficiency, relatively short analysis time, and the small consumption of analytes and reagents which generates relatively lower operational costs than other methods. This review focuses on the use of CE techniques to examine biological matrices and plant materials for the presence of cannabinoids and other bioactive compounds found in cannabis. The advantages, drawbacks, and applicability of the various electromigration approaches are also assessed. The article provides an overview of the “state of the art” and the latest trends in CE-based methods for the determination of cannabinoids.

In recent years, hemp oils have become ubiquitous in health products on the European market. As the trend continues to grow and more cannabinoids are researched for their therapeutic benefits, more academic and industrial interests are drawn to this direction. Cannabidiol, Δ9-tetrahydrocannabinol, and their acidic forms remain the most examined cannabinoids in hemp and cannabis oils, in the case of cannabidiol due to its proven health implications in numerous articles, and in the case of Δ9-tetrahydrocannabinol, due to the legislation in the European area. These oils sold on the internet contain a wide range of cannabinoids that could demonstrate their effects and benefits. As a result of these claims, we developed a robust and rapid method that can identify and quantify 10 of the most common cannabinoids found in hemp oils: cannabivarin, cannabidiolic acid, cannabigerolic acid, cannabigerol, cannabidiol, cannabinol, Δ9-tetrahydrocannabinol, Δ8-tetrahydrocannabinol, cannabichromene, and tetrahydrocannabinolic acid in less than 11 min, with reverse-phase–high-performance liquid chromatography–photodiode matrix system (RP–UHPLC–PDA) equipped with C18 column, eluting in a gradient using water and acetonitrile with formic acid as mobile phases. The quantification of 9 sample products presented in different matrixes was performed using a calibration curve obtained by analyzing standard solutions from a 10-cannabinoid-mix-certified reference standard. The developed method demonstrated the ability to identify and quantify the main cannabinoids in hemp oil and is a useful tool for pharmaceutical professionals.