Pharmaceuticals

17 pages, 2122 KiB

Open AccessArticle

Antibacterial Activity and Molecular Docking of Lignans Isolated from Artemisia cina Against Multidrug-Resistant Bacteria

by Leslie Cynthia García Hernández, Rosa Isabel Higuera-Piedrahita, Nallely Rivero-Perez, Ana Lizet Morales-Ubaldo, Benjamín Valladares-Carranza, Héctor Alejandro de la Cruz-Cruz, Jorge Alfredo Cuéllar-Ordaz, Cynthia González-Ruiz, María Inés Nicolás-Vázquez and Adrian Zaragoza-Bastida

Pharmaceuticals 2025, 18(6), 781; https://doi.org/10.3390/ph18060781 - 23 May 2025

Abstract

The World Health Organization notes that some bacteria have been demonstrated to possess significant public health risks; they have antibiotic resistance, and there are fewer alternatives for control. The n-hexane extract and cinaguaiacin obtained from Artemisia cina show promising antibacterial activity, including [...] Read more.

The World Health Organization notes that some bacteria have been demonstrated to possess significant public health risks; they have antibiotic resistance, and there are fewer alternatives for control. The n-hexane extract and cinaguaiacin obtained from Artemisia cina show promising antibacterial activity, including against multidrug-resistant bacteria that affect animal and human health. Objective: The aim of this study was to determine the antibacterial activity of the n-hexane extract of A. cina and cinaguaiacin against multidrug-resistant bacteria. Methods:A. cina was collected in the pre-flowering period, the n-hexane extract was obtained, and chromatographic techniques and structure were used to separate the lignans, which were elucidated with nuclear magnetic resonance techniques. Four ATCC strains were used, and four strains were isolated from clinical cases with different resistance profiles. The antibacterial activity was determined by calculating the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), the time-kill kinetics assay, and the cell membrane integrity and DNA release assay. Molecular docking studies of lignans demonstrated the binding mode involved in the active site of DNA gyrase B. Results: The n-hexane extract inhibited growth against 87.5% of the strains tested (MIC 5.31 to 42.5 mg/mL) and showed bactericidal activity against 25% of the strains tested (MBC 0.62 to 85 mg/mL). Cinaguaiacin inhibited growth against 100% of the strains tested (MIC, 0.56 to 2.25 mg/mL) and exhibited bactericidal activity against 25% of the strains tested (MBC, 0.62 to 85 mg/mL). Conclusions: The mechanism of cinaguaiacin’s action may be associated with damage to the plasma membrane, as the protein and DNA levels were higher than those of the positive control. The n-hexane extract and cinaguaiacin obtained from A. cina showed a bacteriostatic or bactericidal effect, depending on the strain evaluated. Full article

(This article belongs to the Special Issue Biomedical Properties, Developments and Therapeutic Potential of Sesquiterpenoid Lactones and Natural Compounds)

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17 pages, 1804 KiB

Open AccessArticle

Difenoconazole-Loaded Nanostructured Lipid Carriers: Preparation, Characterization, and Evaluation

by Yinghong Li, Hu Zhang, Tingting Meng, Yuqin Zhou, Beilei Zhou, Shihan Du, Hong Yuan and Fuqiang Hu

Pharmaceuticals 2025, 18(6), 780; https://doi.org/10.3390/ph18060780 - 23 May 2025

Abstract

Background/Objectives: Difenoconazole (DFC) is a broad-spectrum fungicide. However, its application is limited due to poor aqueous solubility. Drugs with low solubility can be better absorbed using nanostructured lipid carriers (NLCs). Hence, the application of DFC in an NLC delivery system is proposed. [...] Read more.

Background/Objectives: Difenoconazole (DFC) is a broad-spectrum fungicide. However, its application is limited due to poor aqueous solubility. Drugs with low solubility can be better absorbed using nanostructured lipid carriers (NLCs). Hence, the application of DFC in an NLC delivery system is proposed. Methods: Difenoconazole-loaded nanostructured lipid carriers (DFC-NLCs) with different solid–liquid lipid ratios were prepared by solvent diffusion method. Key physicochemical parameters, including particle diameter, surface charge (zeta potential), drug encapsulation efficiency, and morphological characteristics, were systematically characterized. Using Rhizoctonia solani (R. solani) as the model strain, inhibitory efficiency of DFC-NLC dispersion was compared with that of commercial dosage forms, such as 25% DFC emulsifiable concentrate (DFC-EC) and 40% DFC suspension concentrate (DFC-SC). Additionally, uptakes of DFC-NLC dispersions in R. solani were further observed by fluorescence probe technology. The safety profiles of DFC-NLCs and commercial dosage forms were evaluated using zebrafish as the model organism. Acute toxicity studies were conducted to determine the maximum non-lethal concentration (MNLC) and 10% lethal concentration (LC₁₀). Developmental toxicity studies were performed to observe toxic phenotypes. Results: DFC-NLC dispersions were in the nanometer range (≈200 nm) with high zeta potential, spherical in shape with encapsulation efficiency 69.1 ± 1.8%~95.0 ± 2.6%, and drug loading 7.1 ± 0.3%~9.7 ± 0.6% determined by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Compared with commercial dosage forms, the antifungal effect of the DFC-NLC on R. solani was significantly improved in in vitro antibacterial experiments (p < 0.05). The 50% effective concentration (EC₅₀) values were 0.107 mg·L⁻¹ (DFC-NLC), 0.211 mg·L⁻¹ (DFC-EC), and 0.321 mg·L⁻¹ (DFC-SC), respectively. The uptakes of FITC-labeled DFC-NLC demonstrated that an NLC was appropriate to deliver DFC into pathogen to enhance the target effect. In safety assessment studies, DFC-NLCs exhibited a superior safety profile compared with commercial formulations (p < 0.05). Conclusions: This study investigates the feasibility of NLCs as delivery systems for poorly water-soluble fungicides, demonstrating their ability to enhance antifungal efficacy and reduce environmental risks. Full article

(This article belongs to the Section Pharmaceutical Technology)

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15 pages, 236 KiB

Open AccessReview

Scientific Justification and Policy Recommendations to the US Food and Drug Administration for Waiving Comparative Efficacy Studies

by Sarfaraz K. Niazi

Pharmaceuticals 2025, 18(6), 779; https://doi.org/10.3390/ph18060779 - 23 May 2025

Abstract

This detailed review looks at how the rules for proving biosimilarity are changing, mainly focusing on the requirements for comparative efficacy studies (CESs). As analytical technologies progress, mounting evidence suggests that when we establish robust analytical similarity and pharmacokinetic equivalence, CESs become less [...] Read more.

This detailed review looks at how the rules for proving biosimilarity are changing, mainly focusing on the requirements for comparative efficacy studies (CESs). As analytical technologies progress, mounting evidence suggests that when we establish robust analytical similarity and pharmacokinetic equivalence, CESs become less valuable. This review combines findings from over 600 studies on biosimilars found in PubMed (showing that no biosimilar with proven analytical similarity has ever failed a CES), looks at the differences in global regulations on this topic, and explains how the Food and Drug Administration’s pharmacokinetic testing rules for biosimilars are similar to the bioequivalence testing for generics. Finally, specific changes to the Biologics Price Competition and Innovation Act (BPCIA) are suggested to make US rules match the growing global scientific agreement, which could lower development costs and speed up patient access to biosimilars while still keeping safety and effectiveness intact. Full article

(This article belongs to the Special Issue Biosimilars Development Strategies)

17 pages, 3491 KiB

Open AccessArticle

Discovery of Novel CRK12 Inhibitors for the Treatment of Human African Trypanosomiasis: An Integrated Computational and Experimental Approach

by Qin Li, Jiayi Luo, Chenggong Fu, Wenqingqing Kang, Lingling Wang, Henry Tong, Zhaorong Lun, Qianqian Zhang, Dehua Lai and Huanxiang Liu

Pharmaceuticals 2025, 18(6), 778; https://doi.org/10.3390/ph18060778 - 23 May 2025

Abstract

Background: Human African trypanosomiasis (HAT), caused by Trypanosoma brucei, is a neglected tropical disease with limited treatments, highlighting the pressing need for new drugs. Cell division cycle-2-related kinase 12 (CRK12), a pivotal protein involved in the cell cycle regulation of T. brucei [...] Read more.

Background: Human African trypanosomiasis (HAT), caused by Trypanosoma brucei, is a neglected tropical disease with limited treatments, highlighting the pressing need for new drugs. Cell division cycle-2-related kinase 12 (CRK12), a pivotal protein involved in the cell cycle regulation of T. brucei, has emerged as a promising therapeutic target for HAT, yet effective CRK12 inhibitors remain lacking. Methods: An integrated strategy combining computational modeling, virtual screening, molecular dynamics (MD) simulations, and experimental validation was adopted to discover potential inhibitors against CRK12. By using the predicted and refined 3D structure of CRK12 from AlphaFold2 and MD simulation, over 1.5 million compounds were screened based on multiple-scale molecular docking, and 26 compounds were selected for evaluation of biological activity based on anti-T. brucei bioassays. Dose–response curves were generated for the most potent inhibitors, and the interaction mechanism between the top four compounds and CRK12 was explored by MD simulations and MM/GBSA binding free energy analysis. Results: Of the 26 compounds, six compounds demonstrated sub-micromolar to low-micromolar IC₅₀ values (0.85–3.50 µM). The top four hits, F733-0072, F733-0407, L368-0556, and L439-0038, exhibited IC₅₀ values of 1.11, 1.97, 0.85, and 1.66 µM, respectively. Binding free energy and energy decomposition analyses identified ILE335, VAL343, PHE430, ALA433, and LEU482 as hotspot residues for compound binding. Hydrogen bonding analysis demonstrated that these compounds can form stable hydrogen bonds with the hinge residue ALA433, ensuring their stable binding within the active site. Conclusions: This study establishes a robust and cost-effective pipeline for CRK12 inhibitor discovery, identifying several novel inhibitors demonstrating promising anti-HAT activity. The newly discovered scaffolds exhibit structural diversity distinct from known CRK12 inhibitors, providing valuable lead compounds for anti-trypanosomal drug development. Full article

(This article belongs to the Special Issue Novel Drug Targets and Drug Candidates for Neglected Tropical Diseases)

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13 pages, 223 KiB

Open AccessArticle

Safety Profile of Antipsychotics as Predictors of the Quality of Life in Patients with Schizophrenia—An Inpatient Welfare Institution-Based Cross-Sectional Study

by Aleksandra D. Petrovic, Ana M. Barjaktarevic, Olivera Z. Kostic, Sara S. Mijailovic, Slobodan M. Jankovic, Marija V. Andjelkovic, Marijana S. Stanojevic Pirkovic, Katarina D. Parezanovic Ilic, Vladimir S. Janjic, Jana Mojsilovic, Jana Arsenijevic, Danijela B. Jovanovic, Sanja Knezevic, Nevena Folic, Milovan Stevic, Dejana Ruzic Zecevic, Nemanja Z. Petrovic and Marina J. Kostic

Pharmaceuticals 2025, 18(6), 777; https://doi.org/10.3390/ph18060777 - 23 May 2025

Abstract

Background/Objectives: Adverse effects of antipsychotics represent a significant limiting factor in achieving favorable therapeutic outcomes in the treatment of schizophrenia, and may contribute to a diminished quality of life among affected individuals. The primary objective of this study was to identify and [...] Read more.

Background/Objectives: Adverse effects of antipsychotics represent a significant limiting factor in achieving favorable therapeutic outcomes in the treatment of schizophrenia, and may contribute to a diminished quality of life among affected individuals. The primary objective of this study was to identify and evaluate the adverse effects of antipsychotics in patients diagnosed with schizophrenia who were treated at the social welfare institution, as well as to analyze the impact of these adverse effects on patients’ overall quality of life. Methods: A clinical, observational cross-sectional study was conducted, involving a sample of 278 patients diagnosed with schizophrenia. The patients were assessed in terms of their sociodemographic and clinical characteristics. Adverse effects of antipsychotics were evaluated using The Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale, while quality of life was assessed in the previous study. Results: The average number of adverse effects per patient with schizophrenia was 3.56 for psychiatric, 1.18 for neurological, 2.62 for autonomic, and 7.12 for other side effects. The average UKU score was 17.22 ± 11.04, with significant differences based on accommodation, antipsychotic type, and dosing regimen. UKU scores were negatively correlated with the EuroQoL 5-Dimension 5-Level (EQ-5D-5L) index, Visual Analog Scale (VAS) score, the Quality-of-Life Enjoyment and Satisfaction Questionnaire—Short Form (Q-LES-Q-SF) score, and the scores of physical and psychological domains of the World Health Organization Quality-of-Life Scale (WHOQOL-BREF). Conclusions: The findings of this study suggest that the presence of antipsychotic-related adverse effects is a significant determinant that can negatively influence the quality of life in patients with schizophrenia. These results underscore the importance of an individualized approach when determining pharmacological treatment strategies in the management of schizophrenia. Full article

(This article belongs to the Section Pharmacology)

18 pages, 2563 KiB

Open AccessArticle

PLASMOpred: A Machine Learning-Based Web Application for Predicting Antimalarial Small Molecules Targeting the Apical Membrane Antigen 1–Rhoptry Neck Protein 2 Invasion Complex

by Eugene Lamptey, Jessica Oparebea, Gabriel Anyaele, Belinda Ofosu, George Hanson, Patrick O. Sakyi, Odame Agyapong, Dominic S. Y. Amuzu, Whelton A. Miller III, Samuel K. Kwofie and Henrietta Esi Mensah-Brown

Pharmaceuticals 2025, 18(6), 776; https://doi.org/10.3390/ph18060776 - 23 May 2025

Abstract

Objective: Falciparum malaria is a major global health concern, affecting more than half of the world’s population and causing over half a million deaths annually. Red cell invasion is a crucial step in the parasite’s life cycle, where the parasite invade human erythrocytes [...] Read more.

Objective: Falciparum malaria is a major global health concern, affecting more than half of the world’s population and causing over half a million deaths annually. Red cell invasion is a crucial step in the parasite’s life cycle, where the parasite invade human erythrocytes to sustain infection and ensure survival. Two parasite proteins, Apical Membrane Antigen 1 (AMA-1) and Rhoptry Neck Protein 2 (RON2), are involved in tight junction formation, which is an essential step in parasite invasion of the red blood cell. Targeting the AMA-1 and RON2 interaction with inhibitors halts the formation of the tight junction, thereby preventing parasite invasion, which is detrimental to parasite survival. This study leverages machine learning (ML) to predict potential small molecule inhibitors of the AMA-1–RON2 interaction, providing putative antimalaria compounds for further chemotherapeutic exploration. Method: Data was retrieved from the PubChem database (AID 720542), comprising 364,447 inhibitors and non-inhibitors of the AMA-1–RON2 interaction. The data was processed by computing Morgan fingerprints and divided into training and testing with an 80:20 ratio, and the classes in the training data were balanced using the Synthetic Minority Oversampling Technique. Five ML models developed comprised Random Forest (RF), Gradient Boost Machines (GBMs), CatBoost (CB), AdaBoost (AB) and Support Vector Machine (SVM). The performances of the models were evaluated using accuracy, F1 score, and receiver operating characteristic—area under the curve (ROC-AUC) and validated using held-out data and a y-randomization test. An applicability domain analysis was carried out using the Tanimoto distance with a threshold set at 0.04 to ascertain the sample space where the models predict with confidence. Results: The GBMs model emerged as the best, achieving 89% accuracy and a ROC-AUC of 92%. CB and RF had accuracies of 88% and 87%, and ROC-AUC scores of 93% and 91%, respectively. Conclusions: Experimentally validated inhibitors of the AMA-1–RON2 interaction could serve as starting blocks for the next-generation antimalarial drugs. The models were deployed as a web-based application, known as PLASMOpred. Full article

(This article belongs to the Special Issue Artificial Intelligence-Assisted Drug Discovery)

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22 pages, 8985 KiB

Open AccessArticle

Huanglian Jiedu Decoction Treats Ischemic Stroke by Regulating Pyroptosis: Insights from Multi-Omics and Drug–Target Relationship Analysis

by Yixiao Gu, Zijin Sun, Tao Li and Xia Ding

Pharmaceuticals 2025, 18(6), 775; https://doi.org/10.3390/ph18060775 - 23 May 2025

Abstract

Background: Ischemic stroke (IS) is a severe condition with limited therapeutic options. Pyroptosis, a type of programmed cell death linked to inflammation, is closely associated with IS-related damage. Studies suggest inflammation aligns with the traditional Chinese medicine (TCM) concept of “fire-heat syndrome”. Huanglian [...] Read more.

Background: Ischemic stroke (IS) is a severe condition with limited therapeutic options. Pyroptosis, a type of programmed cell death linked to inflammation, is closely associated with IS-related damage. Studies suggest inflammation aligns with the traditional Chinese medicine (TCM) concept of “fire-heat syndrome”. Huanglian Jiedu Decoction (HLJD), a TCM formula known for clearing heat and purging fire, has shown therapeutic effects on IS, potentially by regulating pyroptosis. Study design: Eight-week-old male mice were divided into six groups: sham operation, model, positive drug, and low-, medium-, and high-dose HLJD groups. After a week of adaptive feeding, mice received respective treatments for five days, followed by modeling on the sixth day, with samples collected 23 h post-perfusion. Analyses included multi-omics, physiology, histopathology, virtual drug screening, target affinity assessment, and molecular biology techniques to measure relevant indicators. Results: HLJD effectively mitigated IS-related damage, maintaining neurological function, reducing ischemic levels, protecting cellular morphology, inhibiting neuronal apoptosis, and preserving blood–brain barrier integrity. Bioinformatics of high-throughput omics data revealed significant activation of pyroptosis and related inflammatory pathways in IS. ScRNA-seq identified neutrophils, macrophages, and microglia as key pyroptotic cell types, suggesting potential therapeutic targets. Network pharmacology and molecular docking identified NLRP3 as a critical target, with 6819 ligand–receptor docking results. SPR molecular fishing, LC-MS, molecular dynamics, and affinity measurements identified small molecules with high affinity for NLRP3. Molecular biology techniques confirmed that HLJD regulates pyroptosis via the classical inflammasome signaling pathway and modulates the inflammatory microenvironment. Conclusions: Following IS, pyroptosis in myeloid cells triggers an inflammatory cascade, leading to neural damage. HLJD may inhibit NLRP3 activity, reducing pyroptosis and associated inflammation, and ultimately mitigating damage. Full article

(This article belongs to the Special Issue Novel Drug Compositions for Ischemic Stroke: Mechanisms and Clinical Applications)

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26 pages, 5216 KiB

Open AccessArticle

Cystoseira spinosa Polysaccharide: A Promising Natural Source for Antioxidant, Pro-Angiogenic, and Wound Healing Applications: In Silico Study

by Mouhamed Ayad Berfad, Intissar Kammoun, Marwa Lakhrem, Zakaria Boujhoud, Malek Eleroui, Manel Mellouli, Saadia Makni, Majed Kammoun, Riadh Badraoui, Jean Marc Pujo, Hatem Kallel and Ibtissem Ben Amara

Pharmaceuticals 2025, 18(6), 774; https://doi.org/10.3390/ph18060774 - 23 May 2025

Abstract

Background/Objectives: This study evaluated the potential of a polysaccharide (PCS) extracted from the brown alga Cystoseira spinosa as an antioxidant and anti-inflammatory agent. Collected off the coast of Alkhoms, Libya, PCS was investigated for its wound-healing and pro-angiogenic properties, addressing the need for [...] Read more.

Background/Objectives: This study evaluated the potential of a polysaccharide (PCS) extracted from the brown alga Cystoseira spinosa as an antioxidant and anti-inflammatory agent. Collected off the coast of Alkhoms, Libya, PCS was investigated for its wound-healing and pro-angiogenic properties, addressing the need for natural bioactive compounds in therapeutic applications. Methods: The monosaccharide composition of PCS was analyzed using HPLC-RID, identifying glucuronic acid and xylose as major components. In vitro tests assessed antioxidant activity, while in vivo experiments on 24 rats evaluated wound healing. Rats were divided into four groups: control (saline), standard drug (CYTOL CENTELLA cream), glycerol, and glycerol+PCS. Wound healing was analyzed macroscopically, histologically, and biochemically. The chick chorioallantoic membrane (CAM) model assessed pro-angiogenic effects, and computational analyses explored COX-2 and VEGF pathways. Pharmacokinetic properties were also evaluated. Results: PCS demonstrated significant antioxidant activity and accelerated wound healing after 16 days, with improved wound appearance scores and increased collagen content. Histological analysis confirmed PCS outperformed the standard drug. The CAM model showed PCS increased blood vessel density, length, and junctions while reducing lacunarity. Computational analyses supported involvement of COX-2 and VEGF pathways. Pharmacokinetic assessments indicated good bioavailability, non-inhibition of CYP enzymes, and favorable skin permeability. Conclusions: PCS shows promise as a natural bioactive polymer for wound healing and tissue regeneration. Its antioxidant, anti-inflammatory, and pro-angiogenic properties, combined with favorable pharmacokinetics, highlight its therapeutic potential. This study provides new insights into the mechanisms of C. spinosa polysaccharides and their application in promoting tissue repair. Full article

(This article belongs to the Section Natural Products)

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11 pages, 952 KiB

Open AccessArticle

A Classification-Based Blood–Brain Barrier Model: A Comparative Approach

by Ralph Saber and Sandy Rihana

Pharmaceuticals 2025, 18(6), 773; https://doi.org/10.3390/ph18060773 - 22 May 2025

Abstract

Background and Objectives: Drug permeability across the blood–brain barrier (BBB) remains a significant challenge in drug discovery, prompting extensive efforts to develop in silico predictive models. Most existing models rely on molecular descriptors to characterize drug properties. Feature selection algorithms play a [...] Read more.

Background and Objectives: Drug permeability across the blood–brain barrier (BBB) remains a significant challenge in drug discovery, prompting extensive efforts to develop in silico predictive models. Most existing models rely on molecular descriptors to characterize drug properties. Feature selection algorithms play a crucial role in identifying the most relevant descriptors, thereby enhancing prediction accuracy. Methods: In this study, we compare the effectiveness of sequential feature selection (SFS) and genetic algorithms (GAs) in optimizing descriptor selection for BBB permeability prediction. Five different classifiers were initially trained on a dataset using eight molecular descriptors. Each classifier was then retrained using the descriptors selected by SFS and GA separately. Results: The results indicate that the GA method outperformed SFS, leading to a higher prediction accuracy (96.23%) when combined with a support vector machine (SVM) classifier. Furthermore, the GA approach, utilizing a fitness function based on classifier performance, consistently improved prediction accuracy across all tested models, whereas SFS showed lower effectiveness. Additionally, this study highlights the critical role of polar surface area in determining drug permeability across the BBB. Conclusions: These findings suggest that genetic algorithms provide a more robust approach than sequential feature selection for identifying key molecular descriptors in BBB permeability prediction. Full article

(This article belongs to the Special Issue Drug Delivery across the Blood–Brain Barrier)

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26 pages, 2656 KiB

Open AccessArticle

Unveiling the Polypharmacological Potency of FDA-Approved Rebamipide for Alzheimer’s Disease

by Israa J. Hakeem, Hadil Alahdal, Hanadi M. Baeissa, Tahani Bakhsh, Misbahuddin Rafeeq, Alaa Hamed Habib, Mohammed Matoog Karami, Maryam A. AL-Ghamdi, Ghadeer Abdullah and Abeer Al Tuwaijri

Pharmaceuticals 2025, 18(6), 772; https://doi.org/10.3390/ph18060772 - 22 May 2025

Abstract

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterised by the accumulation of neurotoxic substances in the brain, ultimately leading to progressive cognitive decline. The complex aetiology and involvement of multiple molecular targets in AD pathogenesis have made discovering effective therapeutic agents [...] Read more.

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterised by the accumulation of neurotoxic substances in the brain, ultimately leading to progressive cognitive decline. The complex aetiology and involvement of multiple molecular targets in AD pathogenesis have made discovering effective therapeutic agents particularly challenging. Targeting multiple proteins simultaneously with a single therapeutic agent may offer a promising strategy to address the disease’s multifaceted nature. Methods: This study employed advanced computational methodologies to perform multitargeted molecular docking of FDA-approved drugs against four key AD-associated proteins implicated in disease progression. Among the screened compounds, Rebamipide—a drug conventionally used for treating gastrointestinal disorders—demonstrated notable binding affinities across all targets. Pharmacokinetic predictions, interaction fingerprinting, WaterMap analysis, density functional theory (DFT) calculations, and 100 ns MD simulations were performed for each protein–ligand complex to evaluate its multitarget potential. Results: Rebamipide bound effectively to the NR1 ligand-binding core, suggesting modulation of glutamatergic signalling while reducing β-secretase production and regulating neurotransmitter homeostasis through inhibiting monoamine oxidase-A. Furthermore, Rebamipide enhanced cholinergic neurotransmission by inhibiting human acetylcholinesterase, potentially improving cognitive function. Pharmacokinetic analyses confirmed favourable drug-like properties. Molecular interaction fingerprints revealed consistent hydrogen bonding, hydrophobic contacts, and π-π stacking interactions. WaterMap analysis indicated thermodynamically favourable water displacement upon binding, enhancing ligand affinity. DFT analysis of Rebamipide showed a 4.24 eV HOMO-LUMO gap, with ESP values ranging from −6.63 × 10⁻² to +6.63 × 10⁻² A.U., indicating reactive sites. TDDFT predicted strong UV absorption at 314 nm with a peak intensity of ~6500 L mol⁻¹ cm⁻¹. MD simulations over 100 ns demonstrated minimal structural deviations and stable ligand–protein complexes, reinforcing its multitarget efficacy. Conclusions: The comprehensive in silico investigation highlights Rebamipide as a promising multitargeted therapeutic candidate for Alzheimer’s disease. Its ability to modulate multiple pathogenic pathways simultaneously underscores its potential utility; however, these computational findings warrant further experimental validation to confirm its efficacy and therapeutic relevance in AD. Full article

(This article belongs to the Special Issue Structural and Computationally Driven Molecule Design in Drug Discovery: 2nd Edition)

32 pages, 4062 KiB

Open AccessArticle

Chemical Composition and Anti-Lung Cancer Activities of Melaleuca quinquenervia Leaf Essential Oil: Integrating Gas Chromatography–Mass Spectrometry (GC/MS) Profiling, Network Pharmacology, and Molecular Docking

by Eman Fikry, Raha Orfali, Shagufta Perveen, Safina Ghaffar, Azza M. El-Shafae, Maher M. El-Domiaty and Nora Tawfeek

Pharmaceuticals 2025, 18(6), 771; https://doi.org/10.3390/ph18060771 - 22 May 2025

Abstract

Background/Objectives: This study investigates the phytochemical composition and anticancer activity of Melaleuca quinquenervia leaf essential oil (MQLEO) from Egypt. Methods: Chemical profiling was performed using GC/MS. Anticancer activity was assessed through cytotoxicity screening against multiple cancer cell lines, with a subsequent evaluation of [...] Read more.

Background/Objectives: This study investigates the phytochemical composition and anticancer activity of Melaleuca quinquenervia leaf essential oil (MQLEO) from Egypt. Methods: Chemical profiling was performed using GC/MS. Anticancer activity was assessed through cytotoxicity screening against multiple cancer cell lines, with a subsequent evaluation of cell migration, apoptosis, and cell cycle analysis on the most sensitive line (A549). Network pharmacology and molecular docking analyses were employed to identify potential molecular targets and pathways. Results: GC/MS analysis revealed a unique profile dominated by 1,8-cineole (31.57%), α-pinene isomers (both 1R and 1S forms, collectively 21.26%), and sesquiterpene alcohols (viridiflorol: 13.65%; ledol: 4.55%). These results diverge from prior studies, showing a 25.63% decrease in 1,8-cineole and no detectable α-terpineol, suggesting environmental, genetic, or methodological impacts on biosynthesis. In vitro tests revealed selective cytotoxicity against A549 lung cancer cells (IC₅₀ = 18.09 μg/mL; selectivity index = 4.30), meeting NCI criteria. Staurosporine was used as a positive control to validate the assays, confirming the reliability of the methods. MQLEO also inhibited cell migration (62–68% wound closure reduction) and induced apoptosis (24.32% vs. 0.7% in controls). Cell cycle arrest at the G₀-G₁ phase implicated cyclin-dependent kinase regulation. Network pharmacology identified ESR1, CASP3, PPARG, and PTGS2 as key targets, with MQLEO components engaging apoptosis, inflammation (TNF, IL-17), and estrogen pathways. Conclusions: MQLEO demonstrates promising anticancer activity through multiple mechanisms including apoptosis induction, cell cycle arrest, and migration inhibition. The multi-target activity profile highlights its potential as a therapeutic candidate for lung cancer, warranting further in vivo validation and pharmacokinetic studies to advance clinical translation. Full article

(This article belongs to the Special Issue Medicinal Plants: Exploring Plant-Based Bioactive Compounds for Cancer and Metabolic Diseases Prevention and Intervention)

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25 pages, 7954 KiB

Open AccessArticle

Comprehensive GC-MS Profiling and Multi-Modal Pharmacological Evaluations of Haloxylon griffithii: In Vitro and In Vivo Approaches

by Iram Iqbal, Mohamed A. M. Ali, Fatima Saqib, Kinza Alamgir, Mohammad S. Mubarak, Anis Ahmad Chaudhary, Mohamed El-Shazly and Heba A. S. El-Nashar

Pharmaceuticals 2025, 18(6), 770; https://doi.org/10.3390/ph18060770 - 22 May 2025

Abstract

Background/Objectives: Haloxylon griffithii is a medicinal plant possessing therapeutic effects in disorders associated with the gastrointestinal (GIT) system. This research aims to study the pharmacological activity of Haloxylon griffithii in a multidimensional manner, involving phytochemistry screening and in vitro and in vivo [...] Read more.

Background/Objectives: Haloxylon griffithii is a medicinal plant possessing therapeutic effects in disorders associated with the gastrointestinal (GIT) system. This research aims to study the pharmacological activity of Haloxylon griffithii in a multidimensional manner, involving phytochemistry screening and in vitro and in vivo experiments. Methods: The whole dried plant was extracted with 80% methanol and further fractionation using solvents of increasing polarity. GC-MS analysis was performed on the crude extract to discover volatile compounds. The spasmolytic/spasmogenic effect was assessed in isolated rabbit jejunum using spontaneous and K⁺-induced contractions, as well as contractions induced by increasing concentrations of calcium ions in depolarized tissue. Antidiarrheal activity was evaluated in Swiss albino rats/mice (n = 6/group) using castor oil-induced diarrhea and peristaltic index models. In silico ADMET screening was conducted via SwissADME and pkCSM. Results: The GC-MS profiling of H. griffithii revealed the presence of 59 phytochemicals and a rare azulene derivative and constituents, including α-santonin and hexadecanoic acid esters, with favorable pharmacokinetic profiles, as predicted using SwissADME and pkCSM computational tools. The in vitro and in vivo experiments revealed the significant calcium channel blocking activity in non-polar fractions (n-hexane and ethyl acetate), while the polar extracts (ethanolic, aqueous) exhibited cholinergic effects, indicating a dual mode of action. Conclusions: This was a first-time demonstration of both antidiarrheal and smooth muscle-relaxant activity in H. griffithii, supported by GC-MS profiling and pharmacological assay. The findings lend scientific credibility to the traditional use of the plant in community healthcare, while also reinforcing the need for further pharmacological and clinical studies to explore its potential in drug development. Full article

(This article belongs to the Special Issue Promising Natural Products in New Drug Design and Therapy)

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14 pages, 752 KiB

Open AccessArticle

Technology Transfer of O-(2-[18F] Fluoroethyl)-L-Tyrosine (IASOglio^®) Radiopharmaceutical

by Anna Notaro, Salvatore Limpido, Lucie Plougastel, Alessandro Zega, Mauro Telleschi, Mauro Quaglierini, Alessia Danti, Antonio Fiore, Letizia Guiducci and Michela Poli

Pharmaceuticals 2025, 18(6), 769; https://doi.org/10.3390/ph18060769 - 22 May 2025

Abstract

Background/Objectives: Gliomas, including the most aggressive subtype—glioblastoma multiforme, are brain tumors with an unfavorable prognosis and high mortality. Early diagnosis is essential to improve treatment efficacy. Positron emission tomography PET with O-(2-[¹⁸F] fluoroethyl)-L-tyrosine ([¹⁸F]FET) has been supported by [...] Read more.

Background/Objectives: Gliomas, including the most aggressive subtype—glioblastoma multiforme, are brain tumors with an unfavorable prognosis and high mortality. Early diagnosis is essential to improve treatment efficacy. Positron emission tomography PET with O-(2-[¹⁸F] fluoroethyl)-L-tyrosine ([¹⁸F]FET) has been supported by clinical studies for its role in diagnosis and monitoring the disease. However, the low availability of [¹⁸F]FET in Italy has limited its use in clinical praxis. This study describes the technological transfer of the radiopharmaceutical IASOglio^® (the commercial [¹⁸F]FET developed by Curium Pharma in Italy), with the aim of improving national access to this advanced diagnostic technology. Methods: Three consecutive batches were produced using the automated Trasis AllinOne module, and quality control was performed, including chemical and microbiological tests, to successfully validate the production process. Additionally, the stability of the radiopharmaceutical for its entire shelf life has been demonstrated with stability testing at 14 h after end of synthesis (EOS). Results: The production of [¹⁸F]FET achieved a non-corrected yield between 49% and 52%, with a corrected decay rate ranging from 73% to 79%. The process met the required quality specifications, including bio-burden control and filter integrity. The technological transfer was successfully completed, and production authorization was obtained from the Italian Medicines Agency (AIFA) for the Officina Farmaceutica of Institute of Clinical Physiology of the National Research Council (CNR-IFC) located in Pisa. Conclusions: Local production of [¹⁸F]FET in Italy marks a milestone in glioma diagnosis, thereby contributing to timely treatment and improved clinical outcomes. Full article

(This article belongs to the Special Issue Development of Novel Radiopharmaceuticals for SPECT and PET Imaging)

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24 pages, 3234 KiB

Open AccessArticle

Uncovering the Advantages of Foam Dressings with Active Ingredients

by Daniela Chrysostomou, Georgios E. Papanikolaou, Lorraine Boshoff, Thandazi Mbele, Andrea Pokorná, Adéla Holubová, Frank A. D. T. G. Wagener and Niels A. J. Cremers

Pharmaceuticals 2025, 18(6), 768; https://doi.org/10.3390/ph18060768 - 22 May 2025

Abstract

Background/Objectives: Foam dressings are designed for their ability to manage exudate and are selected to optimize wound repair. Various foam dressings are available, ranging from basic polyurethane to more sophisticated options, incorporating active components to combat infections or foster healing. This study investigates [...] Read more.

Background/Objectives: Foam dressings are designed for their ability to manage exudate and are selected to optimize wound repair. Various foam dressings are available, ranging from basic polyurethane to more sophisticated options, incorporating active components to combat infections or foster healing. This study investigates the requirements for the most suitable foam dressing through a combination of field research, laboratory testing, and clinical evaluation. Methods: We tested 17 foam dressings commonly used by wound care professionals while attending an international conference. An effective foam dressing should absorb wound fluid for several days, as wound care professionals value absorption and retention capacity, often favoring less frequent changing dressings, preferably twice a week or even weekly. Results: The foam dressings tested can absorb the expected amount of exudate typically produced by different wound types. There is some variability in retention capacity and product prices, resulting in differences in cost-effectiveness among products. In addition, some dressings are enriched with active ingredients that can accelerate healing through their antimicrobial and anti-inflammatory properties, such as foam dressings infused with silver or honey. A honey-based foam dressing was evaluated in a clinical survey involving eight wound care specialists, and four clinical cases with varying wound pathologies were discussed in more detail to highlight its key properties. Conclusions: Ideally, a foam dressing should have adequate absorption and retention capacities, effectively resolve and prevent infections, protect against external trauma, ensure optimal patient comfort without damaging newly formed granulation tissue, accelerate wound healing processes, and reduce wound care time (e.g., remaining in place for 7 days). Together, these factors make honey- or silver-loaded foam dressings more cost-effective than plain dressings due to their antimicrobial activities and ability to nourish tissues. Full article

(This article belongs to the Special Issue Applications of Beehive Products for Wound Repair and Skin Care)

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17 pages, 1571 KiB

Open AccessArticle

Quantum Drugs (Q-Drugs): A New Discovery and Taboo Breaking Approach; Producing Carbon Quantum Dots from Drug Molecules

by Gamze Camlik, Besa Bilakaya, Gökçe Karaotmarlı Güven, Esra Küpeli Akkol, Zelihagül Degim, Eduardo Sobarzo-Sánchez and Ismail Tuncer Degim

Pharmaceuticals 2025, 18(6), 767; https://doi.org/10.3390/ph18060767 - 22 May 2025

Abstract

Background/Objectives: Carbon quantum dots (CQDs) are carbon-based structures with particle sizes ranging from 1 to 10 nm. They can be prepared using various carbon sources, including those doped with heteroatoms. CQDs exhibit unique optoelectronic properties, high photostability, low toxicity, and exceptional biocompatibility. It [...] Read more.

Background/Objectives: Carbon quantum dots (CQDs) are carbon-based structures with particle sizes ranging from 1 to 10 nm. They can be prepared using various carbon sources, including those doped with heteroatoms. CQDs exhibit unique optoelectronic properties, high photostability, low toxicity, and exceptional biocompatibility. It was aimed to produce CQDs from active pharmaceutical ingredients (APIs). Methods: This study introduces a novel class of CQDs synthesized directly from APIs, which we term “Quantum Drugs” (Q-Drugs). We present several APIs alongside detailed methods for Q-Drug synthesis and characterization. We describe the necessary structural properties for forming Q-Drugs and provide the values for particle size, polydispersity index, and zeta potential that were obtained from various drug molecules. Results: The particle sizes were determined with the size of 7.360 ± 0.030 nm and 10.000 ± 0.022 nm; polydispersity indexes of 10.500 ± 1.230 and 32.610 ± 1.401; and zeta potentials of −3.400 ± 0.054 mV and −40.000 ± 0.142 mV, respectively using different APIs. Conclusions: This study successfully demonstrated the synthesis and characterization of Q-Drugs, a novel class of CQD derived from APIs. The results provide valuable data on the physicochemical properties of these Q-Drugs, paving the way for further investigation into their potential applications. Full article

(This article belongs to the Special Issue From the Simple to the Complex in the Formation of Supramolecular Devices Based on Cyclodextrins and Polymer Derivatives Applied in the Scope of Health)

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28 pages, 1526 KiB

Open AccessReview

Microbiota-Accessible Borates as Novel and Emerging Prebiotics for Healthy Longevity: Current Research Trends and Perspectives

by Andrei Biţă, Ion Romulus Scorei, Marvin A. Soriano-Ursúa, George Dan Mogoşanu, Ionela Belu, Maria Viorica Ciocîlteu, Cristina Elena Biţă, Gabriela Rău, Cătălina Gabriela Pisoschi, Maria-Victoria Racu, Iurie Pinzaru, Alejandra Contreras-Ramos, Roxana Kostici, Johny Neamţu, Viorel Biciuşcă and Dan Ionuţ Gheonea

Pharmaceuticals 2025, 18(6), 766; https://doi.org/10.3390/ph18060766 - 22 May 2025

Abstract

Precision nutrition-targeted gut microbiota (GM) may have therapeutic potential not only for age-related diseases but also for slowing the aging process and promoting longer healthspan. Recent studies have shown that restoring a healthy symbiosis of GM by counteracting dysbiosis (DYS) through precise nutritional [...] Read more.

Precision nutrition-targeted gut microbiota (GM) may have therapeutic potential not only for age-related diseases but also for slowing the aging process and promoting longer healthspan. Recent studies have shown that restoring a healthy symbiosis of GM by counteracting dysbiosis (DYS) through precise nutritional intervention is becoming a major target for extending healthspan. Microbiota-accessible borate (MAB) complexes, such as boron (B)–pectins (rhamnogalacturonan–borate) and borate–phenolic esters (diester chlorogenoborate), have a significant impact on healthy host–microbiota symbiosis (HMS). The mechanism of action of MABs involves the biosynthesis of the autoinducer-2–borate (AI-2B) signaling molecule, B fortification of the mucus gel layer by the MABs diet, inhibition of pathogenic microbes, and reversal of GM DYS, strengthening the gut barrier structure, enhancing immunity, and promoting overall host health. In fact, the lack of MAB complexes in the human diet causes reduced levels of AI-2B in GM, inhibiting the Firmicutes phylum (the main butyrate-producing bacteria), with important effects on healthy HMS. It can now be argued that there is a relationship between MAB-rich intake, healthy HMS, host metabolic health, and longevity. This could influence the deployment of natural prebiotic B-based nutraceuticals targeting the colon in the future. Our review is based on the discovery that MAB diet is absolutely necessary for healthy HMS in humans, by reversing DYS and restoring eubiosis for longer healthspan. Full article

(This article belongs to the Special Issue Boron-Containing Compounds: Identification, Synthesis, Biological Actions and Pharmacology)

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27 pages, 3525 KiB

Open AccessArticle

Enhancing the Drug Release and Physicochemical Properties of Rivaroxaban via Cyclodextrin Complexation: A Comprehensive Analytical Approach

by Cristina Solomon, Valentina Anuța, Iulian Sarbu, Emma Adriana Ozon, Adina Magdalena Musuc, Veronica Bratan, Adriana Rusu, Vasile-Adrian Surdu, Cătălin Croitoru, Abhay Chandak, Roxana Mariuca Gavriloaia, Teodora Dalila Balaci, Denisa Teodora Niță and Mirela Adriana Mitu

Pharmaceuticals 2025, 18(6), 761; https://doi.org/10.3390/ph18060761 - 22 May 2025

Abstract

Background/Objectives: Rivaroxaban, an oral anticoagulant, shows poor aqueous solubility, posing significant challenges to its bioavailability and therapeutic efficiency. The present study investigates the improvement of rivaroxaban’s solubility through the formation of different inclusion complexes with three cyclodextrin derivatives, such as β-cyclodextrin (β-CD), [...] Read more.

Background/Objectives: Rivaroxaban, an oral anticoagulant, shows poor aqueous solubility, posing significant challenges to its bioavailability and therapeutic efficiency. The present study investigates the improvement of rivaroxaban’s solubility through the formation of different inclusion complexes with three cyclodextrin derivatives, such as β-cyclodextrin (β-CD), methyl-β-cyclodextrin (Me-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD) prepared by lyophilization in order to stabilize the complexes and improve dissolution characteristics of rivaroxaban. Methods: The physicochemical properties of the individual compounds and the three lyophilized complexes were analysed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Results: FTIR spectra confirmed the formation of non-covalent interactions between rivaroxaban and the cyclodextrins, suggesting successful encapsulation into cyclodextrin cavity. SEM images revealed a significant morphological transformation from the crystalline structure of pure rivaroxaban and cyclodextrins morphologies to a more porous and amorphous matrix in all lyophilized complexes. XRD patterns indicated a noticeable reduction in drug crystallinity, supporting enhanced potential of the drug solubility. TGA analysis demonstrated improved thermal stability in the inclusion complexes compared to the individual drug and cyclodextrins. Pharmacotechnical evaluation revealed that the obtained formulations (by comparison with physical mixtures formulations) possessed favorable bulk and tapped density values, suitable compressibility index, and good flow properties, making all suitable for direct compression into solid dosage forms. Conclusions: The improved cyclodextrins formulation characteristics, combined with enhanced dissolution profiles of rivaroxaban comparable to commercial Xarelto^® 10 mg, highlight the potential of both cyclodextrin inclusion and lyophilization technique as synergistic strategies for enhancing the solubility and drug release of rivaroxaban. Full article

(This article belongs to the Special Issue From the Simple to the Complex in the Formation of Supramolecular Devices Based on Cyclodextrins and Polymer Derivatives Applied in the Scope of Health)

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27 pages, 4318 KiB

Open AccessArticle

Unveiling Therapeutic Powers of Indigenous Flora: Antimicrobial, Antioxidant, and Anticancer Properties of Horwoodia dicksoniae

by Khadijah A. Altammar

Pharmaceuticals 2025, 18(5), 765; https://doi.org/10.3390/ph18050765 - 21 May 2025

Abstract

Background: Horwoodia dicksoniae Turrill. (Brassicaceae) and Stipa capensis Thunb. (Poaceae) are commonly grown in the eastern region of Saudi Arabia. Methods: This study evaluated the antibacterial and antifungal potential of these plants. H. dicksoniae extract was further subjected to antioxidant, anticancer, [...] Read more.

Background: Horwoodia dicksoniae Turrill. (Brassicaceae) and Stipa capensis Thunb. (Poaceae) are commonly grown in the eastern region of Saudi Arabia. Methods: This study evaluated the antibacterial and antifungal potential of these plants. H. dicksoniae extract was further subjected to antioxidant, anticancer, GC-MS, LC-MS/MS, and in silico analyses. Results: H. dicksoniae extract presented a higher antimicrobial efficiency than S. capensis extract by effectively inhibiting the growth of Staphylococcus aureus, Escherichia coli, Proteus vulgaris, Bacillus subtilis, and Candida albicans. H. dicksoniae ethanolic extract also demonstrated promising antioxidant and anticancer properties against the human colon cancer cell line HCT-116. GC-MS analysis revealed the presence of 12 natural compounds in the H. dicksoniae extract, whereas LC-MS/MS analysis revealed 19 different compounds in negative ion mode and 25 in positive ion mode. Furthermore, the presence of bioactive compounds in the H. dicksoniae extract, such as flavonoids (acacetin and hesperetin) and caffeic acid, confirmed the observed antibacterial, antifungal, antioxidant, and anticancer activities. Molecular docking revealed promising interactions between various bioactive compounds and target proteins associated with antimicrobial, antioxidant, and anticancer activities. Conclusions: This study is the first to report GC-MS and LC-MS/MS analyses of H. dicksoniae ethanolic extract. The findings provide valuable insights into the potential mechanisms and therapeutic applications of the identified bioactive compounds. Thus, the present work can serve as a platform for the isolation of natural compounds from H. dicksoniae extract, which may play a significant role in the discovery and design of new drugs for the treatment of human diseases. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant-Based Pharmaceuticals 2024)

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23 pages, 1563 KiB

Open AccessArticle

Bioactive Compounds, Antioxidant, Cytotoxic, and Genotoxic Investigation of the Standardized Liquid Extract from Eugenia involucrata DC. Leaves

by Monatha Nayara Guimarães Teófilo, Leonardo Gomes Costa, Jamira Dias Rocha, Fernando Gomes Barbosa, Anielly Monteiro de Melo, Grazzielle Guimarães de Matos, Cristiane Maria Ascari Morgado, Amanda Silva Fernandes, Lucas Barbosa Ribeiro de Carvalho, Clayson Moura Gomes, Milton Adriano Pelli de Oliveira, Joelma Abadia Marciano de Paula, Elisa Flávia Luiz Cardoso Bailão and Leonardo Luiz Borges

Pharmaceuticals 2025, 18(5), 764; https://doi.org/10.3390/ph18050764 - 21 May 2025

Abstract

Background: Eugenia involucrata DC., a Cerrado native plant, is recognized for its medicinal properties. However, its bioactive compounds remain inadequately explored. Objectives: This study investigated bioactive compounds from a standardized liquid extract from E. involucrata leaves that can act with antioxidant, [...] Read more.

Background: Eugenia involucrata DC., a Cerrado native plant, is recognized for its medicinal properties. However, its bioactive compounds remain inadequately explored. Objectives: This study investigated bioactive compounds from a standardized liquid extract from E. involucrata leaves that can act with antioxidant, cytogenotoxic, cytoprotective, and genoprotective effects. Methods: The phenolic compounds in the standardized liquid extract from E. involucrata leaves were screened by HPLC-DAD. The capture of the free radicals DPPH, ABTS⁺, and the metal reduction power FRAP determined the antioxidant potential. Cytotoxicity was evaluated in RAW 264.7 macrophages (MTT assay), and (anti)cytotoxic and (anti)genotoxic effects were assessed in human lymphocytes using the Trypan blue exclusion method and comet assay, respectively. Results: The extracts present key phenolic compounds, such as ellagic acid, myricitrin, and epicatechin gallate. The standardized extract demonstrated antioxidant capacity, evidenced by its ability to reduce iron and scavenge free radicals. The liquid extract from E. involucrata leaves exhibited cytotoxic effects on RAW 264.7 macrophages at higher concentrations, while demonstrating (anti)cytotoxic activity on human lymphocytes from all tested concentrations. The highest concentration tested of the standardized liquid extract from E. involucrata leaves (250 µg/mL) showed genotoxicity against human lymphocytes compared to the negative control. In contrast, the lowest concentration (62.5 µg/mL) exhibited an antigenotoxic effect on human lymphocytes, reducing the genotoxicity of doxorubicin by approximately 27%. Conclusions: The bioactive compounds in the standardized liquid extract from E. involucrata leaves exhibited antioxidant and antigenotoxic properties, suggesting potential value for nutraceutical and pharmaceutical applications, particularly those related to oxidative stress associated withaging and disease progression. Full article

(This article belongs to the Special Issue Bioactive Compounds From Plants and Their Therapeutic Applications in Lifestyle-Related Diseases)

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