Articles

Abstract

Humulus lupulus L., commonly known as hops, has been cultivated for its role in brewery, but contemporary research reveals its much broader pharmacological and therapeutic potential. This review comprehensively examines the multifaceted biological activities of hops, emphasizing its rich phytochemical profile – including polyphenols, prenylflavonoids, essential oils, and bitter acids – that contribute to diverse health effects. This plant exhibits potent antioxidant, anti-inflammatory, antimicrobial, phytoestrogenic, sedative, neuroprotective, anticancer, and metabolic-regulating properties. Special attention is given to xanthohumol, a compound of growing interest due to its broad-spectrum bioactivity and therapeutic promise, despite its limited bioavailability. Advances in delivery systems including polymeric micelles, nanoemulsions, and encapsulation techniques, are explored as solutions to enhance its clinical applicability. By integrating botanical, biochemical, and pharmacological perspectives, this article provides a critical synthesis of current knowledge and outlines future directions for research and medical innovation. The multifunctional nature of H. lupulus positions it as a valuable natural source for the development of functional foods, nutraceuticals, and phytopharmaceuticals.

Sagan, B.; Stasiłowicz-Krzemień, A.; Kamiński, A.; Cielecka-Piontek, J.; Fan, P.; Czerny, B. Multiple Faces of Humulus lupulus. Herba Pol. 2025, 71(1), 39–62. https://doi.org/10.5604/01.3001.0055.0694. 

Abstract

Bacopa monnieri, also known as Brahmi or Waterhyssop, is a plant used in Ayurveda for its memory-enhancing properties and control of blood sugar levels. It contains active compounds such as alkaloids, saponins, and cucurbitacins, which have various biological activities. The plant has been studied for its potential in treating Alzheimer’s disease, Parkinson’s disease, attention deficit hyperactivity disorder (ADHD), and depression. Animal studies have shown promising results in reducing symptoms and protecting against neurodegeneration. Concerning safety, Bacopa monnieri has been found to be generally non-toxic, with no serious side effects reported. However, interactions with certain medications and contraindications in conditions like hyperthyroidism should be considered. Further research is needed to determine optimal dosages and ensure safety, especially for pregnant and breastfeeding women. 

Gościniak, A.; Stasiłowicz-Krzemień, A.; Szeląg, M.; Pawlak, J.; Skiera, I.; Kwiatkowska, H.; Nowak, N.; Bernady, K.; Trzaskoma, P.; Zimak-Krótkopad, O.; et al. Bacopa monnieri: Preclinical and Clinical Evidence of Neuroactive Effects, Safety of Use and the Search for Improved Bioavailability. Nutrients 2025, 17, 1939. https://doi.org/10.3390/nu17111939 

Abstract

Hops (Humulus lupulus L.) are widely recognized for their use in brewing, but they also possess significant pharmacological properties due to their rich bioactive compounds, with many varieties exhibiting diverse characteristics. This study investigates the chemical composition and biological activities of extracts from six hop varieties, focusing on quantifying xanthohumol and lupulone using High-Performance Liquid Chromatography (HPLC) and Total Phenolic Content (TPC) analysis. The hop varieties demonstrated significant variability in bioactive compound concentrations, with Aurora showing the highest xanthohumol (0.665 mg/g) and Zwiegniowski the highest lupulone (9.228 mg/g). TPC analysis revealed Aurora also had the highest phenolic content (22.47 mg GAE/g). Antioxidant activities were evaluated using DPPH, ABTS, CUPRAC, and FRAP assays, with Aurora and Oregon Fuggle displaying the most potent capacities. Aurora, in particular, showed the highest activity across multiple assays, including significant acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase inhibition, with IC50 values of 24.39 mg/mL, 20.38 mg/mL, and 9.37 mg/mL, respectively. The chelating activity was also assessed, with Apolon demonstrating the strongest metal ion binding capacity (IC50 = 1.04 mg/mL). Additionally, Aurora exhibited the most effective hyaluronidase inhibition (IC50 = 10.27 mg/mL), highlighting its potential for anti-inflammatory applications. The results underscore the influence of genetic and environmental factors on the bioactive compound profiles of hop varieties and their biological activity offering promising avenues for pharmaceutical and nutraceutical applications. However, further studies are needed to fully understand the potential interactions between hop cones components. 

Sagan, B.; Czerny, B.; Stasiłowicz-Krzemień, A.; Szulc, P.; Skomra, U.; Karpiński, T.M.; Lisiecka, J.; Kamiński, A.; Kryszak, A.; Zimak-Krótkopad, O.; et al. Anticholinesterase Activity and Bioactive Compound Profiling of Six Hop (Humulus lupulus L.) Varieties. Foods 2024, 13, 4155. https://doi.org/10.3390/foods13244155 

Abstract

Background: Curcuminoids, the bioactive compounds found in turmeric, exhibit potent antioxidant, anti-inflammatory, and neuroprotective properties. This study aims to enhance the extraction of curcuminoids from turmeric using environmentally friendly solvents supercritical CO2 (scCO2) combined with natural deep eutectic solvents (NADESs) in one process, and to evaluate the resulting biological activity. Methods: A Box–Behnken statistical design was applied to optimize scCO2 extraction conditions—pressure, CO2 volume, and temperature—to maximize curcuminoid yield. Next, the menthol and lactic acid NADESs were selected, and these two solvents were combined into a single turmeric extraction process. The biological activity of the resulting extract was evaluated using antioxidant assays (ferric reducing antioxidant power and 2,2-diphenyl-1-picrylhydrazyl) and enzyme inhibition assays (acetylcholinesterase, butyrylcholinesterase, and tyrosinase). Toxicity assessments were conducted on the aquatic invertebrates Daphnia pulex, Artemia sp., and Chironomus aprilinus. Results: The most effective extraction was achieved using a menthol–lactic acid NADES as a cosolvent, integrated at a 1:20 ratio of plant material to NADESs while in combination with scCO2. The optimized scCO2–NADES extraction resulted in a high curcuminoid yield (33.35 mg/g), outperforming scCO2 extraction (234.3 μg/g), NADESs ultrasound-assisted extraction (30.50 mg/g), and alcohol-based solvents (22.95–26.42 mg/g). In biological assays, the extract demonstrated significant antioxidant activity and effective inhibition of enzymes (acetylcholinesterase, butyrylcholinesterase, and tyrosinase). Toxicity studies showed a concentration-dependent response, with EC50 for Chironomus aprilinus at the level of 0.098 μL/mL and Daphnia pulex exhibiting high sensitivity to the extract. Conclusions: This study highlights the potential of combining NADESs and scCO2 extraction in one process, demonstrating the effectiveness of scCO2–NADES extraction in maximizing curcuminoid yield and enhancing bioactivity.

Stasiłowicz-Krzemień, A.; Wójcik, J.; Gościniak, A.; Szymański, M.; Szulc, P.; Górecki, K.; Cielecka-Piontek, J. Natural Deep Eutectic Solvents Combined with Supercritical Carbon Dioxide for the Extraction of Curcuminoids from Turmeric. Pharmaceuticals 2024, 17, 1596. https://doi.org/10.3390/ph17121596 

Abstract

The therapeutic potential of Cannabis sativa L. extract has gained significant attention due to its diverse medical applications. Sublingual administration remains a common delivery method of cannabinoids; however, challenges often arise due to the inconvenient form of the extract and its taste. To address these issues, a novel bigel formulation was developed, combining water and oil phases to enhance stability and bioavailability. This formulation incorporates a cannabidiol-rich hemp extract, hyaluronic acid for its moisturizing properties, and a taste-masking agent to improve patient compliance and comfort. Using a standardized hemp extract rich in cannabinoids and a well-characterized terpene profile, the printability of the bigels was evaluated through 3D printing technology. A printout with known cannabidiol (CBD) and cannabidiolic acid (CBDA) content of 11.613 mg ± 0.192 of CBD and 4.732 mg ± 0.280 of CBDA in the printout was obtained. In addition, the release profile of CBD and CBDA was evaluated to determine the delivery efficiency of the active ingredient—dissolved active ingredient levels ranged from 74.84% ± 0.50 to 80.87% ± 3.20 for CBD and from 80.84 ± 1.33 to 98.31 ± 1.70 for CBDA depending on the formulation. Rheological studies were conducted to evaluate the viscosity of the bigels under varying temperature conditions, ensuring their stability and usability. Findings suggest that this 3D-printed bigel formulation could significantly enhance the delivery of cannabis extracts, offering a more convenient and effective therapeutic option for patients. This research underscores the importance of innovation in cannabinoid therapies and paves the way for further advancements in personalized medicine. 

Gościniak, A.; Kocaj, F.; Stasiłowicz-Krzemień, A.; Szymański, M.; Karpiński, T.M.; Cielecka-Piontek, J. 3D Printed Bigel: A Novel Delivery System for Cannabidiol-Rich Hemp Extract. Gels 2024, 10, 770. https://doi.org/10.3390/gels10120770 

Abstract

This study delves into the transformative effects of supercritical carbon dioxide (scCO2) cannabis extracts and prebiotic substances (dextran, inulin, trehalose) on gut bacteria, coupled with a focus on neuroprotection. Extracts derived from the Białobrzeska variety of Cannabis sativa, utilising supercritical fluid extraction (SFE), resulted in notable cannabinoid concentrations (cannabidiol (CBD): 6.675 ± 0.166; tetrahydrocannabinol (THC): 0.180 ± 0.006; cannabigerol (CBG): 0.434 ± 0.014; cannabichromene (CBC): 0.490 ± 0.017; cannabinol (CBN): 1.696 ± 0.047 mg/gD). The assessment encompassed antioxidant activity via four in vitro assays and neuroprotective effects against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The extract boasting the highest cannabinoid content exhibited remarkable antioxidant potential and significant inhibitory activity against both enzymes. Further investigation into prebiotic deliveries revealed their proficiency in fostering the growth of beneficial gut bacteria while maintaining antioxidant and neuroprotective functionalities. This study sheds light on the active compounds present in the Białobrzeska variety, showcasing their therapeutic potential within prebiotic systems. Notably, the antioxidant, neuroprotective, and prebiotic properties observed underscore the promising therapeutic applications of these extracts. The results offer valuable insights for potential interventions in antioxidant, neuroprotective, and prebiotic domains. In addition, subsequent analyses of cannabinoid concentrations post-cultivation revealed nuanced changes, emphasising the need for further exploration into the dynamic interactions between cannabinoids and the gut microbiota. 

Sip, S.; Stasiłowicz-Krzemień, A.; Sip, A.; Szulc, P.; Neumann, M.; Kryszak, A.; Cielecka-Piontek, J. Development of Delivery Systems with Prebiotic and Neuroprotective Potential of Industrial-Grade Cannabis sativa L. Molecules 2024, 29, 3574. https://doi.org/10.3390/molecules29153574 

Abstract

The compounds present in hemp show multidirectional biological activity. It is related to the presence of secondary metabolites, mainly cannabinoids, terpenes, and flavonoids, and the synergy of their biological activity. The aim of this study was to assess the activity of the Henola Cannabis sativae extract and its combinations with selected carriers (polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer, magnesium aluminometasilicate, and hydroxypropyl-β-cyclodextrin) in terms of antimicrobial, probiotic, and immunobiological effects. As a result of the conducted research, the antimicrobial activity of the extract was confirmed in relation to the following microorganisms: Clostridium difficile, Listeria monocytogenes, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus pyrogenes, Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, Pseudomonas aereuginosa, and Candida albicans (microorganism count was reduced from ~102 CFU mL−1 to <10 CFU mL−1 in most cases). Additionally, for the system with hydroxypropyl-β-cyclodextrin, a significant probiotic potential against bacterial strains was established for strains Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus rhamnosus, Lactobacillus reuteri, Pediococcus pentosaceus, Lactococcus lactis, Lactobacillus fermentum, and Streptococcus thermophilus (microorganism count was increased from ~102 to 104–107). In terms of immunomodulatory properties, it was determined that the tested extract and the systems caused changes in IL-6, IL-8, and TNF-α levels. 

Stasiłowicz-Krzemień, A.; Szymanowska, D.; Szulc, P.; Cielecka-Piontek, J. Antimicrobial, Probiotic, and Immunomodulatory Potential of Cannabis sativa Extract and Delivery Systems. Antibiotics 2024, 13, 369. https://doi.org/10.3390/antibiotics13040369 

Abstract

Neurological disorders present a wide range of symptoms and challenges in diagnosis and treatment. Cannabis sativa, with its diverse chemical composition, offers potential therapeutic benefits due to its anticonvulsive, analgesic, anti-inflammatory, and neuroprotective properties. Beyond cannabinoids, cannabis contains terpenes and polyphenols, which synergistically enhance its pharmacological effects. Various administration routes, including vaporization, oral ingestion, sublingual, and rectal, provide flexibility in treatment delivery. This review shows the therapeutic efficacy of cannabis in managing neurological disorders such as epilepsy, neurodegenerative diseases, neurodevelopmental disorders, psychiatric disorders, and painful pathologies. Drawing from surveys, patient studies, and clinical trials, it highlights the potential of cannabis in alleviating symptoms, slowing disease progression, and improving overall quality of life for patients. Understanding the diverse therapeutic mechanisms of cannabis can open up possibilities for using this plant for individual patient needs. 

Stasiłowicz-Krzemień, A.; Nogalska, W.; Maszewska, Z.; Maleszka, M.; Dobroń, M.; Szary, A.; Kępa, A.; Żarowski, M.; Hojan, K.; Lukowicz, M.; et al. The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders. Int. J. Mol. Sci. 2024, 25, 5749. https://doi.org/10.3390/ijms25115749 

Abstract

Cannabinoids: cannabidiol (CBD), cannabidiolic acid (CBDA), and cannabichromene (CBC) are lipophilic compounds with limited water solubility, resulting in challenges related to their bioavailability and therapeutic efficacy upon oral administration. To overcome these limitations, we developed co-dispersion cannabinoid delivery systems with the biopolymer polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) and magnesium aluminometasilicate (Neusilin US2) to improve solubility and permeability. Recognizing the potential therapeutic benefits arising from the entourage effect, we decided to work with an extract instead of isolated cannabinoids. Cannabis sativa inflorescences (Henola variety) with a confirming neuroprotective activity were subjected to dynamic supercritical CO2 (scCO2) extraction and next they were combined with carriers (1:1 mass ratio) to prepare the co-dispersion cannabinoid delivery systems (HiE). In vitro dissolution studies were conducted to evaluate the solubility of CBD, CBDA, and CBC in various media (pH 1.2, 6.8, fasted, and fed state simulated intestinal fluid). The HiE-Soluplus delivery systems consistently demonstrated the highest dissolution rate of cannabinoids. Additionally, HiE-Soluplus exhibited the highest permeability coefficients for cannabinoids in gastrointestinal tract conditions than it was during the permeability studies using model PAMPA GIT. All three cannabinoids exhibited promising blood-brain barrier (BBB) permeability (Papp higher than 4.0 × 10−6 cm/s), suggesting their potential to effectively cross into the central nervous system. The improved solubility and permeability of cannabinoids from the HiE-Soluplus delivery system hold promise for enhancement in their bioavailability.