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Keywords = curcumin

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13 pages, 8802 KB  
Article
Protective Effect of Curcumin in Oxidative Stress-Induced Injury on Retinal Pigment Epithelial Cells
by Hyo Seon Yu, Heeyoon Cho, Yong Un Shin, Eun Hee Hong and Seong-Ho Koh
J. Clin. Med. 2025, 14(20), 7153; https://doi.org/10.3390/jcm14207153 - 10 Oct 2025
Abstract
Background/Objectives: Oxidative stress is the major cause of retinal pigment epithelial cell death. We used oxidative stress-injured retinal pigment epithelial cells to investigate the protective effects of curcumin, a strong antioxidant, on the Nod-like receptor protein 3 (NLRP3) inflammasome pathway. Methods: [...] Read more.
Background/Objectives: Oxidative stress is the major cause of retinal pigment epithelial cell death. We used oxidative stress-injured retinal pigment epithelial cells to investigate the protective effects of curcumin, a strong antioxidant, on the Nod-like receptor protein 3 (NLRP3) inflammasome pathway. Methods: To evaluate the effect of curcumin, cell viability was measured with cell counting kit-8 and lactate dehydrogenase assays. Hydrogen peroxide (H2O2)-injured ARPE-19 cells were treated with different curcumin concentrations. We performed a wound healing assay and dichlorodihydrofluorescein diacetate staining. Western blotting and immunofluorescence staining were performed to evaluate the changes in inflammasome levels in the ARPE-19 cells. Result: H2O2 (300 μM) reduced the viability of ARPE-19 cells. However, treatment with 7.5 μM curcumin enhanced ARPE-19 cell viability and reduced cell toxicity. Curcumin also reduced reactive oxygen species (ROS) levels in the H2O2-induced damaged ARPE-19 cells and attenuated the H2O2-dependent levels of the NLRP3 inflammasome and its related signaling proteins. Conclusions: Curcumin demonstrated protective effects against oxidative stress in retinal pigment epithelial cells by attenuating the activation of the NLRP3 inflammasome pathway. These findings suggest the therapeutic potential of curcumin as an anti-inflammatory and antioxidant agent for macular degeneration. Full article
(This article belongs to the Section Ophthalmology)
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24 pages, 4262 KB  
Article
Methylcellulose Bionanocomposite Films Incorporated with Zein Nanoparticles Containing Propolis and Curcumin for Functional Packaging
by Michael Ramos Nunes, Cleonice Gonçalves da Rosa, Gabriel Salvador, Sarah Cardoso de Oliveira Teixeira, Maria Clara Marinho da Costa, Aline da Rosa Almeida, Vanessa Valgas dos Santos, Ana Emília Siegloch, Fernando Domingo Zinger, Jaqueline Suave and Dachamir Hotza
Polysaccharides 2025, 6(4), 91; https://doi.org/10.3390/polysaccharides6040091 - 9 Oct 2025
Abstract
The increasing demand for sustainable alternatives to non-biodegradable plastic packaging is driving the development of active packaging based on biopolymers such as methylcellulose. In this study, innovative methylcellulose nanocomposite films incorporating zein nanoparticles loaded with propolis and curcumin were developed for active packaging [...] Read more.
The increasing demand for sustainable alternatives to non-biodegradable plastic packaging is driving the development of active packaging based on biopolymers such as methylcellulose. In this study, innovative methylcellulose nanocomposite films incorporating zein nanoparticles loaded with propolis and curcumin were developed for active packaging applications. The zein nanoparticles revealed excellent physicochemical properties, with a zeta potential above 30 mV, suggesting adequate stability. Transmission electron microscopy confirmed nanoparticles containing curcumin and propolis with uniform sizes ranging from approximately 130 to 140 nm with low polydispersity. Release studies revealed that approximately 25% of the curcumin and 35% of the propolis were released from the nanoparticles within 24 h. The release mechanism was best described by the Korsmeyer–Peppas model, suggesting a sustained release profile. The nanoparticles reduced the hydrophobicity and rigidity of the films, as evidenced by a lower elastic modulus and higher percentage elongation, thereby suggesting greater flexibility. Fourier Transform Infrared Spectroscopy (FTIR) analysis revealed the incorporation of bioactive compounds in the polymer matrix. Differential scanning calorimetry (DSC) revealed the thermal parameters of the synthesized films. Furthermore, the films exhibited antibacterial and antioxidant activities, making them highly suitable for use as biodegradable active packaging. Full article
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19 pages, 3921 KB  
Article
Curcumin-Functionalized Ag and ZnO Nanoparticles: A Nanotherapeutic Approach for Treating Infections in Diabetic Wounds
by Mahboubeh Dolatyari, Parisa Rostami, Mahya Rostami, Ali Rostami and Hamit Mirtagioglu
Bioengineering 2025, 12(10), 1090; https://doi.org/10.3390/bioengineering12101090 - 9 Oct 2025
Abstract
Chronic wounds, such as diabetic ulcers, remain a significant clinical challenge due to high infection risk and delayed healing. This study presents a comprehensive evaluation of a novel wound dressing incorporating curcumin-functionalized silver–zinc oxide (Ag-ZnO) nanoparticles. The formulation was rationally designed based on [...] Read more.
Chronic wounds, such as diabetic ulcers, remain a significant clinical challenge due to high infection risk and delayed healing. This study presents a comprehensive evaluation of a novel wound dressing incorporating curcumin-functionalized silver–zinc oxide (Ag-ZnO) nanoparticles. The formulation was rationally designed based on molecular docking simulations that identified curcumin as a high-affinity ligand for Staphylococcus aureus Protein A. The synthesized nanoparticles demonstrated potent, broad-spectrum antibacterial activity, achieving complete inhibition of multidrug-resistant pathogens, including MRSA, within 60 s. A critical comparative assessment, incorporating an unloaded Ag-ZnO nanoparticle control group, was conducted in both a rabbit wound model and a randomized clinical trial (n = 75 patients). This design confirmed that the enhanced wound-healing efficacy is specifically attributable to the synergistic effect of curcumin combined with the nanoparticles. The curcumin-loaded Ag-ZnO treatment group showed a statistically significant reduction in healing time compared to both standard care and unloaded nanoparticle controls (e.g., medium wounds: 19.6 days vs. 90.6, p < 0.001). These findings demonstrate that curcumin-functionalized Ag-ZnO nanoparticles offer a safe and highly effective therapeutic strategy, providing robust antibacterial action and significantly accelerated wound healing. Full article
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22 pages, 1330 KB  
Review
Oleosome Delivery Systems: Enhancing Stability and Therapeutic Potential of Natural Products and Xenobiotics
by Marlon C. Mallillin III, Roi Martin B. Pajimna, Shengnan Zhao, Maryam Salami, Raimar Loebenberg and Neal M. Davies
Pharmaceutics 2025, 17(10), 1303; https://doi.org/10.3390/pharmaceutics17101303 - 7 Oct 2025
Viewed by 231
Abstract
Oleosomes are submicron oil bodies of a triacylglycerol core enveloped by a phospholipid monolayer and embedded proteins, forming a naturally assembled nanocarrier with exceptional oxidative resilience, interfacial stability, and biocompatibility. Their unique architecture supports solvent-free extraction, self-emulsification, and near-complete encapsulation of highly lipophilic [...] Read more.
Oleosomes are submicron oil bodies of a triacylglycerol core enveloped by a phospholipid monolayer and embedded proteins, forming a naturally assembled nanocarrier with exceptional oxidative resilience, interfacial stability, and biocompatibility. Their unique architecture supports solvent-free extraction, self-emulsification, and near-complete encapsulation of highly lipophilic compounds (log P > 4), including curcumin and cannabidiol, with reported efficiencies exceeding 95%. These plant-derived droplets enhance oral bioavailability through lymphatic uptake and enable targeted delivery strategies such as magnetically guided chemotherapy, which has reduced tumor burden by approximately 70% in vivo. The review critically examines recent advances in oleosome research, spanning botanical sourcing, green extraction technologies, interfacial engineering, xenobiotic encapsulation, pharmacokinetics, and therapeutic applications across oncology, dermatology, metabolic disease, and regenerative medicine. Comparative analyses demonstrate that oleosomes rival or surpass synthetic lipid nanocarriers in encapsulation efficiency, oxidative stability, and cost efficiency while offering a sustainable, clean-label alternative. Remaining challenges, including low loading of hydrophilic drugs, allergenicity, and regulatory standardization, are addressed through emerging strategies such as hybrid oleosome–liposome systems, recombinant oleosin engineering, and stimulus-responsive coatings. These advances position oleosomes as a versatile and scalable platform with significant potential for food, cosmetic, and pharmaceutical applications. Full article
(This article belongs to the Special Issue Natural Pharmaceuticals Focused on Anti-inflammatory Activities)
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16 pages, 2926 KB  
Article
Synthesis, Characterisation, DFT Study and Biological Evaluation of Complexes Derived from Transition Metal and Mixed Ligands
by Enas H. Mohammed, Eman R. Mohammed, Eman M. Yahya and Mohammed Alsultan
Inorganics 2025, 13(10), 334; https://doi.org/10.3390/inorganics13100334 - 6 Oct 2025
Viewed by 201
Abstract
This research prepared and characterised novel mixed coordination complexes derived from escitalopram with eugenol and curcumin to form (L1) and (L2), respectively. The complexes were prepared via Williamson ether synthesis and analysed by FTIR, UV–Vis, 1H-NMR spectroscopy, elemental [...] Read more.
This research prepared and characterised novel mixed coordination complexes derived from escitalopram with eugenol and curcumin to form (L1) and (L2), respectively. The complexes were prepared via Williamson ether synthesis and analysed by FTIR, UV–Vis, 1H-NMR spectroscopy, elemental analysis, molar conductivity, and magnetic susceptibility. The results confirmed their octahedral geometries. Magnetic investigation reported high-spin configurations for Mn(II), Co(II), and Ni(II) complexes, whereas Cu(II) exhibited a distorted octahedral arrangement with characteristic d–d transitions. In addition, the calculation of Density functional theory (DFT) provided more insight into the detailed structural and electronic properties of the new ligand and its complexes. Antimicrobial compounds were evaluated against Escherichia coli, Staphylococcus aureus, and Candida albicans through the agar well diffusion method. The reported results revealed that Cobalt complexes showed antimicrobial activity followed by Copper (Cu), Nickel (Ni) and Manganese(Mn) complexes, respectively, due to an increase in Co-lipophilicity, which leads to improved diffusion through microbial cell membranes. The research findings confirmed that escitalopram-based mixed ligands coordinate with transition metals and could have significant biological applications. Full article
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19 pages, 847 KB  
Review
Curcumin and Acute Myeloid Leukemia: Synergistic Effects with Targeted Therapy
by Rita Badagliacca, Manlio Fazio, Fabio Stagno, Giuseppe Mirabile, Demetrio Gerace and Alessandro Allegra
Int. J. Mol. Sci. 2025, 26(19), 9700; https://doi.org/10.3390/ijms26199700 - 5 Oct 2025
Viewed by 371
Abstract
Acute myeloid leukemia is characterized by the presence of malignant cells and their uncontrolled growth in bone marrow. Recent studies have been focused on the ability of curcumin, a polyphenol derived from the Curcuma longa plant. The role of curcumin is currently under [...] Read more.
Acute myeloid leukemia is characterized by the presence of malignant cells and their uncontrolled growth in bone marrow. Recent studies have been focused on the ability of curcumin, a polyphenol derived from the Curcuma longa plant. The role of curcumin is currently under investigation, due to its antitumor properties and action on several pathways, including Nuclear Factor kappa-light-chain-enhancer of activated B cells, Signal Transducer and Activator of Transcription 3, Phosphatidylinositol 3-kinase/protein kinase B, and mitogen-activated protein kinase. The aim of this review is to demonstrate the possible anti-leukemic effect of curcumin, thus its ability to induce apoptosis, inhibit cell proliferation, and modulate angiogenesis. Nowadays, although multiple synergistic effects have been observed and curcumin’s efficacy has been demonstrated through several in vivo and in vitro studies, further broad and exhaustive scientific research is needed to confirm the considerable results. In fact, the low bioavailability of curcumin has limited its clinical applications, a challenge that is currently being addressed through the development of nanoformulations to enhance its stability and absorption within the body. In conclusion, curcumin exhibits antitumor properties with a favorable profile, suggesting its potential as a supportive adjunct in the treatment of patients with acute myeloid leukemia. Full article
(This article belongs to the Collection Latest Review Papers in Bioactives and Nutraceuticals)
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15 pages, 1480 KB  
Article
Curcumin Alleviates Doxorubicin-Induced Cardiotoxicity by Modulating Apelin Expression
by Baris Akca, Olcay Murat Disli, Nevzat Erdil, Yilmaz Cigremis, Hasan Ozen, Merve Durhan, Selahattin Tunc, Onural Ozhan, Zeynep Ulutas and Feray Akgul Erdil
Biomolecules 2025, 15(10), 1416; https://doi.org/10.3390/biom15101416 - 5 Oct 2025
Viewed by 287
Abstract
Background: Doxorubicin (Dox)-induced cardiotoxicity is the most important side effect of the drug and significantly limits its use in susceptible patients. Therefore, preventive measures are required to alleviate the Dox-induced cardiac failure. In this study, curcumin, a strong antioxidant agent, was investigated for [...] Read more.
Background: Doxorubicin (Dox)-induced cardiotoxicity is the most important side effect of the drug and significantly limits its use in susceptible patients. Therefore, preventive measures are required to alleviate the Dox-induced cardiac failure. In this study, curcumin, a strong antioxidant agent, was investigated for its potential protective effect on dox-induced cardiotoxicity with its effect on Apelin expression as a mediator of cardiac function. Methods: Wistar albino rats were equally divided into four groups as Control, DOX, CUR, and CUR+DOX. Dox was administered a single dose of 20 mg/kg bw intraperitoneally while 100 mg/kg bw curcumin was given orally for 14 days before the Dox use. Results: DOX group showed a prolonged QT interval on an electrocardiogram and elevated cardiac troponin levels. In biochemical analyses, decreased Superoxide Dismutase activity and increased Malondialdehyde level and Catalase activity were detected in DOX group. Gene expression of Apelin decreased significantly while NF-κB increased in DOX group. Degenerative changes in histopathology, and increased iNOS and nitrotyrosine immunoreactivity were detected in DOX group. However, no significant changes were observed at reduced Glutathione, TNF-, and IL-1β levels. Curcumin use in Dox-given rats altered most of the disturbed parameters investigated in this study, indicating an alleviating effect on Dox-induced cardiotoxicity. Serum and heart Apelin levels and mRNA expression in heart tissue were detected to significantly increase in CUR+DOX group as compared to DOX group. Furthermore, NF-κB mRNA expression was significantly decreased in heart tissue of CUR+DOX group compared with the DOX group. Conclusions: The results suggest that Apelin acts as an important mediator in Dox cardiotoxicity and may be used as a target for treatment of certain cardiomyopathies. By regulating Apelin expression, curcumin may serve as a potential adjunct in cardioprotective approaches. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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21 pages, 2137 KB  
Article
One Pot Synthesis of the C-3 Complex (Curcumin, Demethoxycurcumin, and Bis-Demethoxycurcumin): Their Joint and Independent Biological Actions
by Marco A. Obregón-Mendoza, Rubén Sánchez-Obregón, Rosario Tavera-Hernández, Leidys L. Pérez-González, Antonio Nieto-Camacho, Rogelio Rodríguez-Sotres, Carolina Escobedo-Martínez, Irma Romero and Raúl G. Enríquez
Int. J. Mol. Sci. 2025, 26(19), 9599; https://doi.org/10.3390/ijms26199599 - 1 Oct 2025
Viewed by 332
Abstract
Curcumin (CUR) is the primary metabolite isolated from the Curcuma longa L. rhizome. Most synthetic and biological studies have focused mainly on the curcumin molecule due to its essential biological activity as an antioxidant, anti-cancer, and anti-Alzheimer’s disease agent. However, the natural extract [...] Read more.
Curcumin (CUR) is the primary metabolite isolated from the Curcuma longa L. rhizome. Most synthetic and biological studies have focused mainly on the curcumin molecule due to its essential biological activity as an antioxidant, anti-cancer, and anti-Alzheimer’s disease agent. However, the natural extract of turmeric also contains two essential curcuminoids (demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)), which altogether comprise the so-called C-3 complex. They are present in commercial compositions for treating biliary or digestive ailments. The vegetal rhizome’s extraction typically leads to a mixture of the three main curcuminoids, CUR, DMC, and BDMC, in variable proportions, and each of these metabolites has reported specific synthetic routes. Herein, we have performed the synthesis and isolation of the three major curcuminoids using the method called scrambling of aldehydes followed by aldol di-condensation reactions. A density functional theory (DFT) approach supported the experimental results by inspecting the predicted energies for the aldol condensation. Thus, the di-condensation reaction is substantially favoured (ΔG° = −2685.9 kJ/mol) over the mono-condensation reaction (ΔG° = −1393.753 kJ/mol). Our approach allows us to mimic closely the proportions of these curcuminoids found in extracts from natural sources that follow the order CUR > DMC > BDMC, respectively. The proportion of aldehydes can be modified in the scrambling reaction with an adequate mixture of aldehydes to render the order DMC > CUR > BDMC. This is an advantageous way to increase the amount of the unsymmetric DMC metabolite. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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15 pages, 1939 KB  
Review
Challenges of Ozone Therapy in Periodontal Regeneration: A Narrative Review and Possible Therapeutic Improvements
by Nada Tawfig Hashim, Rasha Babiker, Vivek Padmanabhan, Md Sofiqul Islam, Sivan Padma Priya, Nallan C. S. K. Chaitanya, Riham Mohammed, Shahistha Parveen Dasnadi, Ayman Ahmed, Bakri Gobara Gismalla and Muhammed Mustahsen Rahman
Curr. Issues Mol. Biol. 2025, 47(10), 811; https://doi.org/10.3390/cimb47100811 - 1 Oct 2025
Viewed by 549
Abstract
Ozone (O3) has re-emerged in periodontology for its antimicrobial, oxygenating, and immunomodulatory actions, yet its role in regeneration remains contentious. This narrative review synthesizes current evidence on adjunctive ozone use in periodontal therapy, delineates cellular constraints—especially in periodontal ligament fibroblasts (PDLFs)—and [...] Read more.
Ozone (O3) has re-emerged in periodontology for its antimicrobial, oxygenating, and immunomodulatory actions, yet its role in regeneration remains contentious. This narrative review synthesizes current evidence on adjunctive ozone use in periodontal therapy, delineates cellular constraints—especially in periodontal ligament fibroblasts (PDLFs)—and explores mitigation strategies using bioactive compounds and advanced delivery platforms. Two recent meta-analyses indicate that adjunctive ozone with scaling and root planing yields statistically significant reductions in probing depth and gingival inflammation, with no significant effects on bleeding on probing, plaque control, or clinical attachment level; interpretation is limited by heterogeneity of formulations, concentrations, and delivery methods. Mechanistically, ozone imposes a dose-dependent oxidative burden that depletes glutathione and inhibits glutathione peroxidase and superoxide dismutase, precipitating lipid peroxidation, mitochondrial dysfunction, ATP depletion, and PDLF apoptosis. Concurrent activation of NF-κB and upregulation of IL-6/TNF-α, together with matrix metalloproteinase-mediated extracellular matrix degradation and tissue dehydration (notably with gaseous applications), further impairs fibroblast migration, adhesion, and ECM remodeling, constraining regenerative potential. Emerging countermeasures include co-administration of polyphenols (epigallocatechin-3-gallate, resveratrol, curcumin, quercetin), coenzyme Q10, vitamin C, and hyaluronic acid to restore redox balance, stabilize mitochondria, down-modulate inflammatory cascades, and preserve ECM integrity. Nanocarrier-based platforms (nanoemulsions, polymeric nanoparticles, liposomes, hydrogels, bioadhesive films) offer controlled ozone release and co-delivery of protectants, potentially widening the therapeutic window while minimizing cytotoxicity. Overall, current evidence supports ozone as an experimental adjunct rather than a routine regenerative modality. Priority research needs include protocol standardization, dose–response definition, long-term safety, and rigorously powered randomized trials evaluating bioactive-ozone combinations and nanocarrier systems in clinically relevant periodontal endpoints. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2025)
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33 pages, 3339 KB  
Article
Curcumin–Piperine Self-Nanoemulsifying Delivery in Zanthoxylum rhetsa Seed Oil Attenuates Cuprizone-Induced Frontal Cortex Toxicity
by Mohammad Zubair Alam, Hala Abubaker Bagabir, Mohammad Alameen Faisal Zaher, Thamer M. A. Alqurashi, Badrah S. Alghamdi, Mohsin Kazi, Gamal Said Abd El-Aziz, Gadah Ali Alshahrany, Noor Ahmed Alzahrani, Rafal Mohammed Bakhalgi, Mona Al-Thepyani, Hanin Abdulbaset AboTaleb, Rahaf Saeed Aldhahri, Juweiriya and Ghulam Md Ashraf
Pharmaceuticals 2025, 18(10), 1478; https://doi.org/10.3390/ph18101478 - 1 Oct 2025
Viewed by 316
Abstract
Background/Objectives: Demyelination and neuroinflammation are central features of multiple sclerosis (MS), contributing to motor deficits and cognitive decline. Cuprizone (CPZ)-induced demyelination is a well-established model for studying multiple sclerosis-like neurotoxicity. This study investigated the neuroprotective and immunomodulatory effects of self-nanoemulsifying drug delivery systems [...] Read more.
Background/Objectives: Demyelination and neuroinflammation are central features of multiple sclerosis (MS), contributing to motor deficits and cognitive decline. Cuprizone (CPZ)-induced demyelination is a well-established model for studying multiple sclerosis-like neurotoxicity. This study investigated the neuroprotective and immunomodulatory effects of self-nanoemulsifying drug delivery systems (SNEDDSs) incorporating curcumin, piperine, and Zanthoxylum rhetsa seed oil. Methods: Male mice were divided into five groups: control, CPZ-only, and CPZ co-treated with three nanoformulations BFZ (blank SNEDDS), CFZ (curcumin-SNEDDS), and PFZ (curcumin–piperine SNEDDS). CPZ was administered for 5 weeks, followed by a 2-week recovery or treatment phase. Key neuroinflammatory markers like CD4, CD8, cholinergic (acetylcholinesterase, AChE), myelin integrity (MBP), BDNF, CREB, TNFα, Il-1β were assessed at weeks 5 and 7 using ELISA. Alterations in antioxidant enzymes, brain histology, and behavioral outcomes were also investigated. Results: At week 5, CPZ significantly increased CD4 and CD8 expression and reduced AChE and MBP levels, indicating neuroinflammation, cholinergic impairment, and demyelination. Nanoformulation treatments (both prophylactic and therapeutic) markedly reduced CD4 and CD8 levels, with PFZ showing the most pronounced effect. AChE activity was significantly restored in all treatment groups, with PFZ and CFZ exceeding baseline levels, suggesting enhanced cholinergic function. MBP levels were highest in PFZ-treated mice, surpassing control values and indicating strong remyelination potential. These improvements persisted and further advanced at week 7, especially in PFZ and CFZ groups. Conclusions: Curcumin-based SNEDDS, particularly PFZ, significantly mitigated CPZ-induced neuroinflammation, promoted remyelination, and restored cholinergic activity in the frontal cortex. These findings highlight the therapeutic potential of bioenhanced curcumin nanoformulations for treating demyelinating and neuroinflammatory disorders. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts)
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22 pages, 4729 KB  
Review
Structure-Based Insights into TGR5 Activation by Natural Compounds: Therapeutic Implications and Emerging Strategies for Obesity Management
by Dong Oh Moon
Biomedicines 2025, 13(10), 2405; https://doi.org/10.3390/biomedicines13102405 - 30 Sep 2025
Viewed by 446
Abstract
TGR5 has emerged as a promising therapeutic target for obesity and metabolic disorders due to its regulatory roles in energy expenditure, glucose homeostasis, thermogenesis, and gut hormone secretion. This review summarizes the structural mechanisms of TGR5 activation, focusing on orthosteric and allosteric ligand [...] Read more.
TGR5 has emerged as a promising therapeutic target for obesity and metabolic disorders due to its regulatory roles in energy expenditure, glucose homeostasis, thermogenesis, and gut hormone secretion. This review summarizes the structural mechanisms of TGR5 activation, focusing on orthosteric and allosteric ligand interactions, toggle switch dynamics, and G protein coupling based on cryo-EM and docking-based models. A wide range of bioactive natural compounds including oleanolic acid, curcumin, betulinic acid, ursolic acid, quinovic acid, obacunone, nomilin, and 5β-scymnol are examined for their ability to modulate TGR5 signaling and elicit favorable metabolic effects. Molecular docking simulations using CB-Dock2 and PDB ID 7BW0 revealed key interactions within the orthosteric pocket, supporting their mechanistic potential as TGR5 agonists. Emerging strategies in TGR5-directed drug development are also discussed, including gut-restricted agonism to minimize gallbladder-related side effects, biased and allosteric modulation to fine-tune signaling specificity, and AI-guided optimization of natural product scaffolds. These integrated insights provide a structural and pharmacological framework for the rational design of safe and effective TGR5-targeted therapeutics. Full article
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34 pages, 4740 KB  
Article
In Silico Design and Computational Elucidation of Hypothetical Resveratrol–Curcumin Hybrids as Potential Cancer Pathway Modulators
by Nil Sazlı and Deniz Karataş
Pharmaceuticals 2025, 18(10), 1473; https://doi.org/10.3390/ph18101473 - 30 Sep 2025
Viewed by 314
Abstract
Background/Objectives: Cancer progression is characterized by the suppression of apoptosis, activation of metastatic processes, and dysregulation of cell proliferation. The proper functioning of these mechanisms relies on critical signaling pathways, including Phosphoinositide 3-kinase/Protein kinase B/mammalian Target of Rapamycin (PI3K/Akt/mTOR), Mitogen-Activated Protein Kinase (MAPK), [...] Read more.
Background/Objectives: Cancer progression is characterized by the suppression of apoptosis, activation of metastatic processes, and dysregulation of cell proliferation. The proper functioning of these mechanisms relies on critical signaling pathways, including Phosphoinositide 3-kinase/Protein kinase B/mammalian Target of Rapamycin (PI3K/Akt/mTOR), Mitogen-Activated Protein Kinase (MAPK), and Signal Transducer and Activator of Transcription 3 (STAT3). Although curcumin and resveratrol exhibit anticancer properties and affect these pathways, their pharmacokinetic limitations, including poor bioavailability and low solubility, restrict their clinical application. The aim of our study was to evaluate the synergistic anticancer potential of curcumin and resveratrol through hybrid molecules rationally designed from these compounds to mitigate their pharmacokinetic limitations. Furthermore, we analyzed the multi-target anticancer effects of these hybrids on the AKT serine/threonine kinase 1 (AKT1), MAPK, and STAT3 pathways using in silico molecular modeling approaches. Methods: Three hybrid molecules, including a long-chain (ELRC-LC) and a short-chain (ELRC-SC) hybrid, an ester-linked hybrid, and an ether-linked hybrid (EtLRC), were designed using the Avogadro software (v1.2.0), and their geometry optimization was carried out using Density Functional Theory (DFT). The electronic properties of the structures were characterized through Frontier Molecular Orbital (FMO), Molecular Electrostatic Potential (MEP), and Fourier Transform Infrared (FTIR) analyses. The binding energies of the hybrid molecules, curcumin, resveratrol, their analogs, and the reference inhibitor were calculated against the AKT1, MAPK, and STAT3 receptors using molecular docking. The stabilities of the best-fitting complexes were evaluated through 100 ns molecular dynamics (MD) simulations, and their binding free energies were estimated using the Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) method. Results: DFT analyses demonstrated stable electronic characteristics for the hybrids. Molecular docking analyses revealed that the hybrids exhibited stronger binding compared to curcumin and resveratrol. The binding energy of −11.4 kcal/mol obtained for the ELRC-LC hybrid against AKT1 was particularly remarkable. Analysis of 100 ns MD simulations confirmed the conformational stability of the hybrids. Conclusions: Hybrid molecules have been shown to exert multi-target mechanisms of action on the AKT1, MAPK, and STAT3 pathways, and to represent potential anticancer candidates capable of overcoming pharmacokinetic limitations. Our in silico-based study provides data that will guide future in vitro and in vivo studies. These rationally designed hybrid molecules, owing to their receptor affinity, may serve as de novo hybrid inhibitors. Full article
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18 pages, 2985 KB  
Article
Multicomponent Synthesis of Multi-Target Quinazolines Modulating Cholinesterase, Oxidative Stress, and Amyloid Aggregation Activities for the Therapy of Alzheimer’s Disease
by Saida Chakhari, José Marco-Contelles, Isabel Iriepa, Maria do Carmo Carreiras, Fakher Chabchoub, Lhassane Ismaili and Bernard Refouvelet
Molecules 2025, 30(19), 3930; https://doi.org/10.3390/molecules30193930 - 30 Sep 2025
Viewed by 269
Abstract
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta (Aβ) peptide, intracellular neurofibrillary tangles (NFTs), severe neuronal loss, and a marked decline in cholinergic function. Due to the limited efficacy of currently available therapies, the search for new [...] Read more.
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta (Aβ) peptide, intracellular neurofibrillary tangles (NFTs), severe neuronal loss, and a marked decline in cholinergic function. Due to the limited efficacy of currently available therapies, the search for new chemical scaffolds able to target multiple pathological mechanisms remains an urgent priority. Among the most promising strategies are heterocyclic frameworks that can simultaneously interact with cholinesterase (ChE) enzymes and inhibit amyloid-β (Aβ) aggregation while also exhibiting antioxidant activity. In this context, we report a series of quinazoline derivatives synthesized via a sequential, one-pot multicomponent reaction, in good yields. Several of these compounds demonstrated notable antioxidant properties, as well as inhibitory effects on ChE activity and Aβ1-42 self-aggregation, highlighting their potential as multifunctional agents for the treatment of neurodegenerative disorders. Notably, 2-ethyl-4-(3,4-Dimethoxyphenyl)aminoquinazoline (3h) demonstrated the most balanced biological profile among the tested compounds, exhibiting an ORAC value of 5.73 TE, an acetylcholinesterase (AChE) inhibition IC50 = 6.67 μM, and 36.68% inhibition of Aβ1–42 aggregation, closely approaching the activity of curcumin. These findings highlight compound 3h as a promising quinazoline-based hit for the development of multifunctional agents targeting AD. Full article
(This article belongs to the Special Issue Trends of Drug Synthesis in Medicinal Chemistry)
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17 pages, 2004 KB  
Article
A Comparative Study of Soy Protein Isolate-κ-Carrageenan Emulsion Gels and Bigels for the Encapsulation, Protection, and Delivery of Curcumin
by Emmanueline T Gray, Weining Huang, Zhongkai Zhou, Hao Cheng and Li Liang
Gels 2025, 11(10), 782; https://doi.org/10.3390/gels11100782 - 30 Sep 2025
Viewed by 261
Abstract
Protein-based emulsion gels and bigels serve as ideal delivery systems owing to their distinctive structural properties, high encapsulation efficiency, and adjustable digestive behavior. However, limited research has examined the differences between emulsion gels and bigels as polyphenol delivery systems. In this study, oil-in-water [...] Read more.
Protein-based emulsion gels and bigels serve as ideal delivery systems owing to their distinctive structural properties, high encapsulation efficiency, and adjustable digestive behavior. However, limited research has examined the differences between emulsion gels and bigels as polyphenol delivery systems. In this study, oil-in-water (O/W)-type emulsion gels formulated with soy protein isolate (SPI) and κ-carrageenan (κ-CG) were fabricated using a cold-set gelation method, and then the bigels were prepared through further oil gelation by the addition of glycerol monostearate (GMS). Both SPI-κ-CG emulsion gels and bigels were mainly stabilized by electrostatic and hydrophobic interactions, exhibiting high gel strength, varying from 940 g to 1304 g, and high water holding capacity (~84%). Both the SPI-κ-CG emulsion gels and bigels demonstrated high curcumin encapsulation efficiency, reaching 98~99%. Stability testing revealed that bigels prepared with 15% and 20% GMS exhibited the highest curcumin retention ratios, with a value of around 78% after storage for 21 days at 25 °C, suggesting that denser network structures more effectively prevent the degradation of the encapsulated compound. During the in vitro simulated gastric digestion, higher GMS content significantly delayed curcumin release by over 7%. Increasing GMS concentration from 0% to 20% elevated lipolysis by over 8% and concurrently improved the release of curcumin by more than 18% during the in vitro simulated intestinal digestion. This study provides comparative insights into polyphenol delivery performance between emulsion gels and bigels, offering valuable guidance for developing functional foods based on gel delivery systems. Full article
(This article belongs to the Special Issue Food Gels: Fabrication, Characterization, and Application)
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Article
Mechanistic Insights into the Physiological and Meat Quality Responses of Broiler Chickens Fed Incremental Turmeric Rhizome Meal
by Uchenna Nonyelum Okonkwo, Christiaan Jacobus Smit and Chidozie Freedom Egbu
Animals 2025, 15(19), 2849; https://doi.org/10.3390/ani15192849 - 29 Sep 2025
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Abstract
Natural products, such as turmeric rhizome meal (TRM), may hold the key to a sustainable solution to antimicrobial resistance rise and antibiotic prohibition in food-producing animals. This study evaluated the effects of dietary TRM at 0 (CON), 0.3 (TRM3), 0.6 (TRM6), and 0.9 [...] Read more.
Natural products, such as turmeric rhizome meal (TRM), may hold the key to a sustainable solution to antimicrobial resistance rise and antibiotic prohibition in food-producing animals. This study evaluated the effects of dietary TRM at 0 (CON), 0.3 (TRM3), 0.6 (TRM6), and 0.9 g/kg (TRM9) on growth, nutrient digestibility, immunity, gut function, nutrient transport biomarkers, microbiome, and meat quality in 280 one-day-old male Ross 308 chicks over a 42-day feeding trial. Birds fed TRM indicated higher body weight gain and lower feed conversion ratio (p < 0.05). The TRM groups promoted higher (p = 0.001) serum immunoglobulin Y, immunoglobulin M, and interleukin-10 compared to the CON. Birds fed CON had higher interleukin-2 (p = 0.025), interleukin-6 (p = 0.027), and TNF-α (p = 0.008) levels compared to the TRM groups. Lactobacillus counts in jejunal villi and crypts were higher in the TRM groups than in the CON (p < 0.05). Dietary TRM increased electrogenic glucose and lysine transport, accompanied by up-regulation of claudin-5, zonula occludens 1, and mucin-2 expression (p < 0.05). In breast muscle, TRM fortification reduced malondialdehyde levels (p < 0.05) while increasing long-chain polyunsaturated fatty acids (p < 0.05). Thus, TRM is a potent, residue-free phytobiotic alternative to conventional antibiotic growth promoters in poultry systems. Full article
(This article belongs to the Section Poultry)
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