Search Results (317)

Fatty acids (FAs) play a crucial role in human physiology, including energy production and serving as signaling molecules. However, a dysregulation in their balance can lead to multiple disorders, such as obesity and metabolic syndrome. These pathological conditions alter the balance between the heart’s energetic substrates, promoting an increased reliance on FAs and decreased cardiac efficiency. A therapeutic application of a non-psychotropic phytocannabinoid, cannabigerol (CBG), seems to be a promising target since it interacts with different receptors and ion channels, including cannabinoid receptors—CB₁ and CB₂, α2 adrenoceptor, or 5-hydroxytryptamine receptor. Therefore, in the current study, we evaluated a concentration-dependent effect of CBG (2.5 µM, 5 µM, and 10 µM) on H9c2 cardiomyocytes in lipid overload conditions. Gas–liquid chromatography and Western blotting techniques were used to determine the cellular lipid content and the level of selected proteins involved in FA metabolism, glucose transport, and the insulin signaling pathway. The glucose uptake assay was performed using a colorimetric method. Eighteen-hour CBG treatment in the highest concentration (10 µM) significantly diminished the accumulation of diacylglycerols (DAGs) and the saturation status of this lipid fraction. Moreover, the same concentration of CBG markedly decreased the level of FA transporters, namely fatty acid translocase (CD36) and plasma membrane fatty acid-binding protein (FABPpm), in the presence of palmitate (PA) in the culture medium. The results of our experiment suggest that CBG can significantly modulate lipid storage and composition in cardiomyocytes, thereby protecting against lipid-induced cellular dysfunction. Full article

Cannabidiol (CBD), a phytocannabinoid commonly isolated from chemotype III Cannabis sativa plants, is known for its therapeutic potential. However, comprehensive information on its bioavailability is still lacking. The key objective of this study was to investigate the impact of specific formulations on CBD delivery to the site of action and, in particular, the brain of experimental animals. As brain tissue is an extremely complex matrix, a highly sensitive method employing liquid chromatography–tandem mass spectrometry (LC-MS/MS) had to be implemented. To make it applicable for multiple analytes, the method was validated for 17 other phytocannabinoids and selected metabolites. Using this method, a pharmacokinetic study was conducted on 200 brain samples collected from rats that had been administered various CBD formulations (carriers) via oral gavage. The peak concentration in brain occurred within 1–2 h; notably, the highest was reached with carriers containing triacylglycerols with the shortest fatty acid chains (caprylic/capric). In addition to the parent compound, 7-hydroxy-cannabidiol and 7-carboxy-cannabidiol were detected, confirming rapid post-administration metabolism. Overall, this research enhances understanding of CBD distribution in the brain and underscores the impact of specific formulations on its bioavailability, offering insights into optimizing CBD-based therapies to be both effective and ‘patient-friendly’. Full article

The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a critical threat to global health, creating an urgent need for novel antimicrobial agents. In this study, we evaluated a small library of natural and semisynthetic phytocannabinoids against a broad panel of MDR Gram-positive bacterial strains, evidencing very good activity in the low µM range. We provide evidence of the antibacterial activity of the two separated enantiomers of cannabidiol, offering novel insights into the stereochemical aspects of their bioactivity. To investigate the possible molecular targets and clarify the mechanism of action, we employed Inverse Virtual Screening (IVS), a computational approach optimized for predicting potential protein–ligand interactions, on three selected MDR bacterial species. Interestingly, key targets belonging to important bacterial metabolic pathways and defense mechanisms were retrieved, and the results were used to rationalize the observed biological activities. To the best of our knowledge, this study marks the first application of IVS to microorganisms, offering a novel strategy for identifying bacterial protein targets. The results pave the way for future experimental validation, structure-based drug design, and the development of novel antibacterial agents. Full article

Cannabis sativa is a remarkable source of bioactive compounds, with over 150 distinct phytocannabinoids identified to date. Among these, cannabinoids are gaining attention as potential therapeutic agents for neurodegenerative diseases. Previous research showed that cannabinol (CBN), a minor cannabinoid derived from Δ⁹-tetrahydrocannabinol, exhibits antioxidant, anti-inflammatory, analgesic, and anti-bacterial effects. The objective of this study was to assess the protective potential of 24 h CBN pre-treatment, applied at different concentrations (5 µM, 10 µM, 20 µM, 50 µM, and 100 µM), in differentiated neuroblastoma × spinal cord (NSC-34) cells. Transcriptomic analysis was performed using next-generation sequencing techniques. Our results reveal that CBN had no negative impact on cell viability at the tested concentrations. Instead, it showed a significant effect on stress response and neuroplasticity-related processes. Specifically, based on the Reactome database, the biological pathways mainly perturbed by CBN pre-treatment were investigated. This analysis highlighted a significant enrichment in the Reactome pathway’s cellular response to stress, cellular response to stimuli, and axon guidance. Overall, our results suggest that CBN holds promise as an adjuvant agent for neurodegenerative diseases by modulating genes involved in neuronal cell survival and axon guidance. Full article

The endocannabinoid system (ECS) is a vital biological network essential for maintaining homeostasis and supporting various physiological functions. It comprises cannabinoid receptors, endogenous lipid-based ligands, known as endocannabinoids, as well as metabolic enzymes and associated proteins responsible for regulating their levels within tissues. The ECS plays a central role in modulating processes involving the central nervous system (CNS). Recent studies have highlighted its antioxidant, anti-inflammatory, and neuroprotective properties. The therapeutic potential of cannabinoids, particularly phytocannabinoids derived from plants, has attracted significant attention in medical and pharmaceutical research. This interest has grown in parallel with the increasing availability of cannabinoid-based food supplements on the pharmaceutical market. Given the complexity of the ECS and its broad range of interactions, the discovery of this system has spurred extensive investigations into the use of cannabinoids for various health conditions. In this review, we examine recent preclinical evidence supporting the use of phytocannabinoids in the context of neurodegenerative diseases, particularly in Alzheimer’s disease and Parkinson’s disease. Targeting the ECS through phytocannabinoid-based pharmacological modulation offers a promising therapeutic strategy for these neurological disorders. Among these compounds, cannabidiol has emerged as a key focus of research due to its multifaceted effects and favorable safety profile. Nonetheless, continued investigation is necessary to clarify its mechanisms of action, and to develop effective, evidence-based clinical applications. Full article

Background: Cannabidiol (CBD), a non-intoxicating phytocannabinoid, has garnered interest as a potential therapeutic agent for managing pain and inflammation associated with upper-quarter disorders, including temporomandibular disorders (TMDs), orofacial pain, myofascial dysfunction, and postoperative dental pain. Methods: This systematic review critically evaluated clinical, preclinical, and mechanistic studies on the efficacy and safety of CBD in the management of such conditions. A total of 10 studies, comprising randomized clinical trials and animal models, met the inclusion criteria and were assessed for methodological quality and risk of bias. Results: The findings suggest that CBD demonstrates analgesic, anti-inflammatory, and muscle-relaxant effects in chronic myofascial TMDs and bruxism, particularly when applied topically or intraorally. In contrast, studies on acute nociceptive pain (e.g., pulpitis, third molar surgery) yielded inconsistent results. Notably, CBD enhanced the effects of conventional analgesics such as opioids and NSAIDs in several preclinical models, indicating synergistic potential. However, substantial heterogeneity in CBD dosage, formulation, administration routes, and outcome measures limited comparability across studies. Adverse effects were minimal in clinical trials, yet underreported. Conclusions: While early evidence supports CBD’s potential as an adjunctive treatment for certain upper-quarter conditions, especially those involving chronic myofascial pain, further high-quality, condition-specific trials are required to establish standardized dosing, delivery methods, and long-term safety. Full article

Bone-associated pathologies are major contributors to chronic pathology statistics. Current gold standard treatments present limitations such as the ability to act as scaffolds whilst effectively delivering medications to promote cellular proliferation. Recent advancements in biomaterials have suggested whey protein isolate (WPI) hydrogel as a potential candidate to act as a scaffold with the capacity for drug delivery for bone regeneration. In this study, we investigate whey protein isolate hydrogels enhanced with the phytocannabinoid cannabidiol (CBD). The use of CBD in WPI hydrogels for bone regeneration is original. The results suggest that CBD was successfully incorporated into the hydrogels bound potentially through hydrophobic interactions formed between hydrophobic patches of the protein and the hydrophobic cannabinoid. The incorporation of CBD into the WPI hydrogels improved the mechanical strength of the hydrogels. The Young’s modulus was improved from 2700 kPa ± 117 kPa to 7100 kPa ± 97 kPa when compared to the WPI control, without plant-derived cannabinoids, to the WPI with the maximum CBD concentration. Furthermore, statistically significant differences for both Young’s modulus and compressive strength were observable between the WPI control and CBD hydrogel variables. The release of CBD from the WPI hydrogels was confirmed with the results suggesting a maximum release of 20 μM over the 5-day period. Furthermore, the hydrogels supported the proliferation and synthesis of collagen and calcium, as well as the alkaline phosphatase activity of MC3T3-E1 pre-osteoblasts, which demonstrates the potential of WPI/CBD hydrogels as a biomaterial for osseous tissue regeneration. Full article

Mesenchymal stem cells isolated from human adipose tissue (hASCs) are a promising tool for tissue repair due to their ability to differentiate into specific cell lineages. The possibility of modulating the adipogenic differentiation of hASCs is crucial in improving their therapeutic potential. This study aimed to investigate the effects of cannabidiol (CBD), a phytocannabinoid isolated from Cannabis sativa L., on hASCs. Few studies have evaluated its role in stem cell (SC) properties and their differentiation potential. hASCs were first treated with different concentrations of CBD (ranging from 0.1 to 10 μM) to assess its effects on viability, demonstrating that this molecule is non-toxic, except at the concentration of 10 μM. Subsequently, the role of CBD in the proliferation, metabolism and adipogenic potential of hASCs was analyzed. CBD promoted adipogenesis in a dose-dependent manner, even in the absence of differentiation medium. This result was evidenced by the presence of lipid vacuoles, the expression of adipogenic markers, cytoskeletal actin rearrangement and modulation in the expression of osteogenic genes. Although the results indicated a role of CBD in promoting hASC adipogenesis, further research will be needed to explore the mechanism of action of CBD in SC differentiation and to deepen its utility in SC-based approaches. Full article

Since the 1990s, cannabis has experienced a gradual easing of access restrictions, accompanied by the expansion of its legalization and commercialization. This shift has led to the proliferation of cannabis-based products, available as cosmetics, food supplements, and pharmaceutical dosage forms. Consequently, there has been a growing demand for reliable and reproducible extraction techniques alongside precise analytical methods for detecting and quantifying cannabinoids, both of which are essential for ensuring consumer safety and product quality. Given the variability in extraction and quantification techniques across laboratories, significant attention has recently been directed toward method validation. Validated methods ensure precise cannabinoid measurement in cannabis-based products, supporting compliance with dosage guidelines and legal limits. Thus, this review highlights recent advancements in these areas, with a particular focus on High-Performance Liquid Chromatography (HPLC) coupled with Ultraviolet (UV) detection, as it is considered the gold standard for cannabinoid analysis included in cannabis monographs present in several pharmacopeias. The research focused on studies published between January 2022 and December 2024, sourced from PubMed, Scopus, and Web of Science, that employed an HPLC-UV analytical technique for the detection of phytocannabinoids. Additionally, the review examines cannabinoid extraction techniques and the validation methodologies used by the authors in the selected papers. Notably, ultrasound extraction has emerged as the most widely utilized technique across various matrices, with Deep Eutectic Solvents (DESs) offering a promising, efficient, and environmentally friendly extraction alternative. Analytical chromatographic separations continue to be predominantly conducted using C18 reversed-phase columns. Nevertheless, in recent years, researchers have explored various stationary phases, particularly to achieve the enantioseparation of cannabinoids. Full article

The deoxynivalenol (DON) mycotoxin poses serious health risks, especially to swine, which are highly susceptible to intestinal damage. Existing strategies to counteract DON toxicity remain insufficient. This study aimed to evaluate the protective effects of cannabidiol (CBD), a phytocannabinoid with anti-inflammatory properties, against DON-induced intestinal toxicity in porcine intestinal epithelial cells. Using differentiated and proliferating porcine intestinal epithelial cells (IPEC-J2), we evaluated CBD (2.5–5 μM) against DON (0.5–50 μM) through viability assays, apoptosis markers (Bax/Bcl-2 ratio), inflammatory mediators (NFκB, IL-6, COX-2), oxidative stress indicators (TXNIP, SOD1, CAT), tight junction gene expression (Claudin-1, Occludin), and barrier permeability. DON exhibited dose- and time-dependent cytotoxicity (IC₅₀ = 2.60 μM at 24 h; 1.07 μM at 48 h). Pre-treatment with 5 μM CBD restored cell viability at low DON concentrations (0.5–2 μM) but failed at ≥8 μM. In differentiated cells, CBD suppressed apoptosis (reduced Bax/Bcl-2 ratio), oxidative stress (downregulated TXNIP; restored CAT expression), and inflammation (decreased IL-6 and COX-2) under high-dose DON (50 μM), while enhancing tight junction protein expression and barrier integrity at 5 μM DON. Conversely, in proliferating cells, CBD exacerbated apoptosis (elevated Bax/Bcl-2 ratio) and inflammatory responses (upregulated IL-6 and COX-2) at subtoxic levels of DON (2 μM). CBD alone induced cytotoxicity at ≥10 μM. Our findings demonstrate that CBD exhibits context-dependent efficacy, providing protection in differentiated epithelia under moderate DON exposure (≤5 μM) but exhibiting detrimental effects in proliferating cells. Its narrow therapeutic window and paradoxical actions necessitate cautious application. These findings position CBD as a potential adjunctive therapy for DON detoxification but highlight critical limitations for standalone use. Full article

Background/Objectives: Cannabigerol (CBG) is a non-psychoactive phytocannabinoid with significant therapeutic potential, showing emerging applications in drug delivery. This study aimed to develop and evaluate CBG-conjugated nanoparticles (NPs) incorporating tubulin-targeting drugs to enhance anticancer activity. Methods: CBG was conjugated with N-desacetylthiocolchicine, paclitaxel, and camptothecin using sebacic acid and 4,4′-dithiodibutyric acid as linkers, and nanoparticles were obtained. The NPs were characterized by their stability and size (hydrodynamic diameters < 90 nm). Their antiproliferative activity was assessed in three human tumor cell lines and non-tumorigenic cells. Their cellular uptake and mechanisms of action were investigated via confocal microscopy and cell cycle analysis. Results: The chemical composition of the linkers significantly influenced the antiproliferative effect, with the NPs containing 4,4′-dithiodibutyric acid demonstrating higher activity. Notably, NP3b, formulated with this linker, exhibited up to an 80-fold increase in antiproliferative potency compared to its sebacic acid counterpart (NP3a). In mesothelioma cells (MSTO-211H), NP3b displayed significantly higher cytotoxicity than in non-tumorigenic mesothelial cells (MeT-5A), indicating selectivity for cancer cells. Further analysis in glioblastoma cells confirmed that the NPs retained the microtubule-disrupting effects of their parent drugs. Conclusions: These findings highlight the potential of CBG-based NPs as versatile nanomedicine platforms for targeted cancer therapy. This study underscores the importance of linker chemistry in modulating therapeutic efficacy and supports the development of multifunctional drug delivery systems. Full article

Background: The gut–brain axis (GBA) is a complex bidirectional communication system that links the gastrointestinal tract and the central nervous system. Essential oils (EOs) have emerged as promising natural compounds capable of modulating this axis. Methods: A comprehensive analysis of the recent literature was conducted, focusing on studies investigating the effects of EOs on the GBA. Particular attention was given to the endocannabinoid system, the role of cannabis-derived EOs, and other plant-based EOs with potential neuroprotective and gut microbiota-modulating effects. Results: Among the EOs analyzed, cannabis essential oil (CEO) gained attention for its interaction with cannabinoid receptors (CBR1 and CBR2), modulating gut motility, immune responses, and neurotransmission. While acute administration of the CEO reduces inflammation and gut permeability, chronic use has been associated with alterations in gut microbiota composition, potentially impairing cognitive function. Other EOs, such as those from rosemary, lavender, eucalyptus, and oregano, demonstrated effects on neurotransmitter modulation, gut microbiota balance, and neuroinflammation, supporting their potential therapeutic applications in GBA-related disorders. Conclusions: EOs demonstrate promising potential in modulating the GBA through mechanisms including neurotransmitter regulation, gut microbiota modulation, and anti-inflammatory activity. At the same time, phytocannabinoids offer therapeutic value; their long-term use warrants caution due to potential impacts on microbiota. Future research should aim to identify EO-based interventions that can synergistically restore GBA homeostasis and mitigate neurodegenerative and gastrointestinal disorders. Full article

Type 2 diabetes mellites (T2DM) is the most common form of diabetes and affects a significant portion of the population. Obesity-related increases in free fatty acids and glucose in the diet contribute to β-cell dysfunction and loss, ultimately leading to the onset of T2DM. The endocannabinoid system, which is present throughout the body, plays a vital role in regulating various physiological processes, including those in the pancreas. This system has been implicated in metabolic disorders like obesity and diabetes, as it helps to regulate appetite, food intake, and fat production. Phytocannabinoids from Cannabis sativa have the potential to influence the endocannabinoid system, offering a promising therapeutic approach for diabetes and its complications. Using high-glucose–high-lipid (HGHL)-induced INS-1 β-cells, we investigated the protective effects of two major (THC and CBD) and three minor (THCV, CBC, and CBG) phytocannabinoids on high glucose–high lipid (HGHL)-induced apoptosis, cell cycle disruption, and impaired function of beta-cells. Our results showed that all five phytocannabinoids reduced HGHL-induced apoptosis, likely by decreasing TXNIP protein levels. Additionally, THC and all three minor phytocannabinoids provided protective effects against functional impairments caused by HGHL exposure. Full article

Cell-based therapy using mesenchymal stem cells (MSCs) shows promise for treating several diseases due to their anti-inflammatory and immunomodulatory properties. To enhance the therapeutic potential of MSCs, in vitro priming strategies have been explored. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, may influence MSC proliferation, differentiation, and immunomodulatory properties. This study evaluates the immunomodulatory potential of equine adipose tissue-derived MSCs (EqAT-MSCs) primed with a CBD-rich cannabis extract. EqAT-MSCs (P3) were primed with CBD concentrations of 5 µM and 7 µM for 24 h. Morphological analysis, MTT assay, β-galactosidase activity, apoptosis assays, and gene expression of interleukins IL-1β, IL-6, IL-10, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) were conducted. Additionally, cannabinoid receptor 1 (CB1) and 2 (CB2) expression were evaluated in naïve EqAT-MSCs (P2–P5). The naïve EqAT-MSCs expressed CB1 and CB2 receptors. Priming with 5 µM significantly increased the expression of IL-10, TNF-α, and IFN-γ, while 7 µM decreased IL-1β and IL-6 expression. No significant changes were observed in other cytokines, MTT, β-galactosidase activity, or apoptosis. These findings demonstrate that naïve EqAT-MSCs express CB1 and CB2 receptors and priming with the extract modulates the expression of pro- and anti-inflammatory cytokines, highlighting its potential immunomodulatory role in EqAT-MSC-based therapies. Full article

The endocannabinoid system (ECS) is a complex endocrine network involved in maintaining body homeostasis. It comprises endocannabinoids, their receptors (CB1 and CB2), and the enzymes and transporters responsible for their synthesis and degradation. While the ECS’s role in the nervous system is well established, its functions in other organs and peripheral tissues, including the cardiovascular, gastrointestinal, and reproductive systems, remain incompletely understood. With the increasing use of marijuana, particularly among individuals of reproductive age, concerns have emerged regarding its potential impact on male and female fertility. Phytocannabinoids (∆9tethrahydrocannabinol and cannabidiol), as well as synthetic cannabimimetic drugs, interact with the ECS, influencing sperm and oocyte physiology and reproductive outcomes. Recent research has identified ECS-related biomarkers with potential applications in infertility diagnosis, particularly in assessing male fertility with greater precision. Furthermore, emerging evidence suggests that ECS signaling pathways are involved in epigenetic modifications, which may influence health maintenance, disease susceptibility, and transgenerational inheritance patterns. These findings highlight the therapeutic potential of ECS modulation in reproductive disorders and broader medical applications. This narrative review aims to elucidate the role of the ECS in human reproduction, with a particular focus on the influence of endocannabinoids on gametogenesis. While current research underscores the critical role of the ECS in fertility, further investigations are needed to fully elucidate its underlying mechanisms and its broader implications for reproductive health and therapeutic interventions. Full article