Browsing by Author "Wojtunik-Kulesza, Karolina"
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Item Advances in Sodium Channel Modulation in Epilepsy Therapy: Focus on Eslicarbazepine, Lacosamide and Cenobamate(MDPI, 2026-07-28) Rudkowska, Monika; Mołdoch, Jarosław; Wronikowska-Denysiuk, Olga; Agacka-Mołdoch, Monika; Pradiuch, Anna; Wojtunik-Kulesza, KarolinaBackground/Objectives: Voltage-gated sodium channels (VGSCs) are among the most important molecular targets in epilepsy therapy. Unlike classical antiseizure medications (ASMs), newer sodium channel modulators selectively affect slow inactivation or persistent sodium currents, potentially improving seizure control while preserving physiological neuronal activity. This review summarizes the pharmacology, mechanisms of action, clinical efficacy, and therapeutic potential of eslicarbazepine acetate, lacosamide, and cenobamate. Methods: A narrative review of published clinical trials, meta-analyses, and real-world evidence was conducted. The analysis focused on sodium channel modulation, pharmacokinetic properties, efficacy in monotherapy and adjunctive therapy, and safety profiles in focal epilepsy. Main findings of the review: Eslicarbazepine acetate and lacosamide primarily enhance slow inactivation of VGSCs, suppressing pathological repetitive neuronal firing with limited effects on normal neuronal signaling. Both agents demonstrated efficacy in monotherapy and add-on therapy, with favorable pharmacokinetic properties and a relatively low potential for drug–drug interactions. Cenobamate represents a novel therapeutic approach through preferential inhibition of persistent sodium currents combined with positive allosteric modulation of GABAA receptors. Clinical trials and real-world studies demonstrated high responder and seizure freedom rates, particularly in patients with drug-resistant focal epilepsy. The most common adverse effects across these agents included dizziness, somnolence, fatigue, and gastrointestinal symptoms, while notable safety concerns included hyponatremia with eslicarbazepine acetate and drug interactions or dose-dependent adverse effects with cenobamate. Conclusions: Recent advances in sodium channel modulation have expanded therapeutic options for focal epilepsy and support the development of more selective, mechanism-based ASM therapies. Eslicarbazepine acetate, lacosamide, and cenobamate demonstrate favorable efficacy and tolerability profiles and may improve seizure control in patients with drug-resistant epilepsy.Item Biological Activity of Monoterpene-Based Scaffolds: A Natural Toolbox for Drug Discovery(MDPI, 2025-03-27) Mołdoch, Jarosław; Agacka-Mołdoch, Monika; Jóźwiak, Grzegorz; Wojtunik-Kulesza, KarolinaOne of the most common strategies used in drug design is the molecular scaffold approach, which combines traditional medicine based on natural active compounds derived from plants with modern synthetic drug development. Designing new compounds based on natural skeletons enables extensive modifications of both bioavailability and biological activity. An excellent example of a natural molecular scaffold is the monoterpenes group, which serves as a core structure for building more complex molecules by attaching various chemical groups. Their ability to interact with biological targets, combined with structural versatility, makes them promising molecular scaffolds in pharmaceutical research and green chemistry applications. This review paper focuses on selected monoterpenes (carvacrol, carvone, citral, menthol, menthone, β-pinene, thymol, and verbenone), which are frequently used as molecular scaffolds. The newly designed derivatives exhibit various biological activities, including anticancer, antibacterial, antiviral, neuroprotective, and many others.Item Development of Gluten-Free Corn Snacks Enriched with White Mulberry Fruit: Polyphenolic Composition, Antioxidant Activity and In Vitro Gastrointestinal Stability of Phenolic Compounds(MDPI, 2026) Kasprzak-Drozd, Kamila; Ziółkiewicz, Agnieszka; Wojtunik-Kulesza, Karolina; Gancarz, Marek; Kowalska, Iwona; Misiurek, Justyna; Wójciak, Magdalena; Sowa, Ireneusz; Oniszczuk, Tomasz; Combrzyński, Maciej; Oniszczuk, AnnaThe aim of this study was to evaluate the effect of adding white mulberry (Morus alba L.) fruit to extruded corn snacks on their polyphenol profile, antioxidant properties, acetylcholinesterase (AChE) inhibitory activity and the preservation of phenolic compounds in an in vitro digestion model. Mixtures of corn grits with 0, 10, 15 and 20% dried mulberry fruit were extruded at temperatures of 100, 120 and 140 ◦C, and then the total polyphenol content (TPC) and antioxidant activity (IC50 for DPPH) were determined. For selected samples (0%, 140—3E; 15% mulberry, 140—9E; mulberry—13E), further antioxidant tests (FRAP, CUPRAC, Fe2+ chelation) were performed, the phenolic compound profile (UHPLC) and AChE inhibition were assessed, and a two-step in vitro digestion was conducted. The addition of mulberry significantly increased TPC- and free-radical-scavenging capacity compared to the control sample, with snacks containing 15% mulberry extruded at 140 ◦C showing approximately a 3.5-fold higher TPC than the control, while dried mulberry fruit itself exhibited about a five-fold higher TPC than this enriched snack. Among the snacks, the most favorable DPPH-radical-scavenging effect was obtained for the variant with 20% mulberry at 120 ◦C (IC50 = 0.176 mg/mL), whereas the mulberry fruit extract reached an IC50 of 0.0926 mg/mL. In a two-step in vitro digestion model, the mulberry-enriched snack with 15% fruit retained 69.3% of its initial TPC after the gastric phase and 33.3% after the intestinal phase, compared with 55.0% and 20.0%, respectively, for the control snack, confirming a partial but meaningful preservation of phenolic compounds under simulated gastrointestinal conditions. UHPLC analysis confirmed that mulberry and the enriched snacks are a rich source of chlorogenic acids and their isomers, as well as quercetin and kaempferol glycosides, which largely survived the two-step in vitro digestion, despite an observed decrease in TPC after the gastric stage and a further reduction after the intestinal stage. At the same time, mulberry extract and mulberry-enriched snacks exhibited high antioxidant activity in all tests conducted and in vitro AChE inhibitory activity, suggesting that Morus alba L. fruit has the potential to be used as a natural functional ingredient in the production of gluten-free snacks with antioxidant and potentially neuroprotective properties.Item Expanding Knowledge about the Influence of Citral on Cognitive Functions—In Vitro, In Vivo and Ex Vivo Studies(MDPI, 2024-06-22) Wojtunik-Kulesza, Karolina; Rudkowska, Monika; Klimek, Katarzyna; Agacka-Mołdoch, Monika; Mołdoch, Jarosław; Michalak, AgnieszkaCitral, a common monoterpene found in numerous plants, is an interesting compound that has been shown to have various biological activities. Although it is widely distributed in nature and there are many studies presenting its biological activities, its anti-neurodegenerative activity, especially under in vivo conditions, is very poorly understood. Thus, this paper aimed to deepen knowledge about citral activity towards factors and symptoms of neurodegeneration. To accomplish this, several comprehensive tests were conducted, including the estimation of butyrylcholinesterase inhibition, the evaluation of hepatotoxicity and the detection of oxidative stress and lipid peroxidation in vitro, as well as an in vivo behavioral assessment using mice models. Additionally, ex vivo determination of level of the compound in the brain and blood of a tested animal was undertaken. The results obtained revealed that citral is able to inhibit butyrylcholinesterase activity and protect hepatic cells against oxidative stress and lipid peroxidation in vitro. Moreover, behavioral tests in vivo indicated that citral (50 mg/kg) improves memory processes associated with acquisition (passive avoidance test), both in acute and subchronic administration. Additionally, we found that the administration of citral at 25 mg/kg and 50 mg/kg did not significantly affect the locomotor activity. Beyond the aforementioned, gas chromatography-mass spectrometry analysis revealed the presence of the compound in the blood and brain after subchronic administration of citral. Taken together, the results obtained in vitro, in vivo and ex vivo clearly indicate that citral is a promising monoterpene that can potentially be used towards cognition improvement.Item Preliminary Assessment of the Neuroprotective Potential of the Above-Ground Parts of Two Carlina Species (Asteraceae)(MDPI, 2026-03-18) Mołdoch, Jarosław; Agacka-Mołdoch, Monika; Soluch, Agata; Rudkowska, Monika; Wojtunik-Kulesza, KarolinaThe aim of this study was to evaluate the phytochemical profile and neuroprotective potential of extracts from underground and aerial parts of two Carlina species: Carlina acaulis (CA) and Carlina vulgaris (CV). Metabolic profiling performed via UHPLC-UV-MS/MS revealed a distinct chemotaxonomic differentiation between the taxa. C. acaulis was defined as a “phenolic-acid” chemotype dominated by 5-O-caffeoylquinic acid (up to 32.11 mg/g in leaves), whereas C. vulgaris was characterized as a “flavonoid” chemotype, distinguished by a unique C-glycoside signature, including carlinoside and schaftoside. A significant aspect of scientific novelty is the first-ever identification of flavonolignans (e.g., salcolin A/B and tricin derivatives) in the roots of both species. In biological assays, the extracts demonstrated a multidirectional neuroprotective mechanism. Good antioxidant properties (DPPH, FRAP assays) were confirmed, particularly in CA leaves and CV inflorescences which revealed 61% of DPPH scavenging, along with the capacity to chelate Fe(II) ions (above 60% for CA inflorescence, CV leaves and CV root), a crucial mechanism in ferroptosis prevention. Furthermore, leaf extracts of both species exhibited effective inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) exceeding 50%, showing kinetic selectivity towards BChE inhibition. These results position Carlina species as a promising source of metabolites supporting the therapy of neurodegenerative diseases.Item S-(+)-Carvone, a Monoterpene with Potential Anti-Neurodegenerative Activity—In Vitro, In Vivo and Ex Vivo Studies(MDPI, 2024) Wojtunik-Kulesza, Karolina; Rudkowska, Monika; Klimek, Katarzyna; Mołdoch, Jarosław; Agacka-Mołdoch, Monika; Budzyńska, Barbara; Oniszczuk, AnnaCarvone, a natural monoterpene, has been identified in various plants, giving them a characteristic scent. Enantiomers (R-(–) and S-(+)) reveal specific biological activities that are successfully used in traditional medicine for their antifungal, antibacterial, antiparasitic, and anti-influenza properties. The presented paper is based on S-(+)-carvone, characterized by a specific caraway scent, which revealed rich biological activities both in vitro and in vivo. Thus, the aim of the study was to evaluate the potential anti-neurodegenerative activity of S-(+)-carvone, including in vitro experiments (butyrylcholinesterase inhibitory, neuro- and hepatotoxicity as well as neuro- and hepatoprotective activity), in vivo (memory acquisition, locomotor activity), and ex vivo (determination of S-(+)-carvone’s level in tissues collected from mice). Results revealed the multidirectional character of S-(+)-carvone. It has been shown that S-(+)-carvone is capable of butyrylcholinesterase inhibition (40% for 0.025 mg applied onto the plate), and neuroprotection and hepatoprotection at selective concentrations against reactive oxygen species generation and lipid peroxidation along with nonhepatotoxicity character. Additionally, multiple-dose administration of the monoterpene at a dose of 100 mg/kg had a positive influence on memory acquisition. Gas chromatography–mass spectrometry analysis of the plasma and the brain showed that S-(+)-carvone can cross the blood–brain barrier and accumulate in the hippocampus (0.217 μg/mg of tissue), a crucial part of the brain associated with cognition and mental functions.Item The Impact of Fresh Blueberry Addition on the Extrusion-Cooking Process, Physical Properties and Antioxidant Potential of Potato-Based Snack Pellets(MDPI, 2025-05) Combrzyński, Maciej; Soja, Jakub; Oniszczuk, Tomasz; Wojtunik-Kulesza, Karolina; Kręcisz, Magdalena; Mołdoch, Jarosław; Biernacka, BeataThe aim of the study was to develop a new generation of potato-based snack granules enriched with fresh blueberries and evaluate the extrusion-cooking process along with selected physical properties. Blueberries were added in varying amounts (10%, 20%, and 30%) as an ingredient for the semi-finished product. The analysis focused on the impact of moisture content, screw speed, and blueberry concentration on extrusion efficiency and product properties. The results showed significant effects of blueberry addition on extrusion-cooking efficiency (14.40 to 37.12 kg/h) and energy consumption (0.003 to 0.021 kWh/kg). Durability, bulk density, water absorption index (WAI) and water solubility index (WSI) were evaluated with values ranging from 95.46 to 97.61%, 345.07 to 547.37 kg/m3, 2.90 to 3.88 g/g and 8.23 to 18.52%. The incorporation of blueberries also eliminated the need for drying, reducing water consumption and energy demand. Additionally, the antioxidant potential of the blueberry-enriched samples was assessed, indicating improved health benefits (DPPH from 22.71 to 94.22%). Based on the results, the incorporation of up to 30% blueberries is recommended for optimal physical properties and enhanced antioxidant activity.