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Curcumin is a hydrophobic polyphenolic compound with potent anti-inflammatory properties. However, whether it can achieve therapeutic effects by alleviating neuroinflammation in patients with Parkinson's disease (PD) and its potential mechanism are still unknown. This study explored the effects of curcumin on neuroinflammation in dopaminergic neurons and deciphered its direct target in the histone deacetylase 6 (HDAC6)-Nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) pathway, revealing the potential role of curcumin in the treatment of Parkinson's disease. Here, we show that curcumin alleviated the degeneration of neurons in a PD model by mitigating the activation of the NLRP3-mediated inflammatory response both in vivo and in vitro. Furthermore, we discovered that curcumin prevented neuroinflammation by blocking the HDAC6-NLRP3 pathway in a PD model. Moreover, overexpression of HDAC6 could eliminate the effect of curcumin on the neuroinflammatory response mediated by NLRP3. Curcumin and the HDAC6 inhibitor WT161 could alleviate neurodegeneration. In addition, activated HDAC6 directly deacetylated NLRP3 at lysine 84 to maintain its stability, which increased the inflammatory response and promoted neurodegeneration. These findings show that curcumin, a neuroinflammation inhibitor, blocks neurodegeneration via the HDAC6-NLRP3 pathway and represents a potentially practical pharmacological approach for treating neuroinflammation-driven neurodegenerative diseases. For the first time, HDAC6 was shown to directly regulate the acetylation of NLRP3., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In recent years, the use of cationic peptides as alternative drugs with anticancer activity has received attention. In this study, the targeted release of curcumin (Cur) and CM11 peptide alone and together against hepatocellular carcinoma (HCC) was evaluated using chitosan nanoparticles (CS NPs) coated with Pres1 that target the SB3 antigen of HCC cells (PreS1-Cur-CM11-CS NPs). SB3 protein is the specific antigen of HCC and the PreS1 peptide is a part of the hepatitis B antigen, which can specifically bind to the SB3 protein. Chitosan was used to prepare NPs. To Cur and CM11 loading, drugs were added to the CS solution in appropriate concentrations. Pres1 was coupled to the surface of the NPs using EDC catalyst to target NPs against HepG2 cells. SEM and DLS analysis confirmed that the PreS1-Cur-CM11-CS NPs had a size of about 132 nm, the ideal size for penetrating the cell membrane. The loading of Cur and CM11 was equal to 87% and 65%, respectively, which had a sustained and better release in the acidic environment than in the physiological environment. The MTT assay showed that PreS1-Cur-CM11-CS NPs act in a targeted and specific manner with the highest toxicity on the HepG2 cells compared to the control by a decrease in viability of about 26% after 48 h based on cell apoptosis. The results showed that PreS1-Cur-CM11-CS NPs are capable of targeted and specific drug release against HepG2 cancer cells and have significant potential to fight this cancer., Competing Interests: Declarations. Ethical approval: The study was confirmed by the Ethics Committee of the Baqiyatullah University of Medical Sciences with approval ID: IR.BMSU.BLC.1402.007. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study investigates the interrelationship between human telomerase reverse transcriptase (hTERT) and ferroptosis in precursor-B (pre-B) acute lymphoblastic leukemia (ALL), specifically examining how hTERT modulation affects ferroptotic cell death pathways. Given that hTERT overexpression characterizes various cancer phenotypes and elevated telomerase activity is observed in early-stage and relapsed ALL, we investigated the molecular mechanisms linking hTERT regulation and ferroptosis in leukemia cells. The experimental design employed Nalm-6 and REH cell lines under three distinct conditions: curcumin treatment, hTERT siRNA knockdown, and their combination. Cell viability and proliferation were assessed via MTT and BrdU assays at 24- and 48-hour intervals post-treatment. Ferroptotic and oxidative markers were quantified using commercial assays, while cell death parameters and gene expression were evaluated through flow cytometry and qRT-PCR analyses. Molecular docking studies were performed to evaluate protein-ligand interactions. Results demonstrated that combined curcumin treatment and hTERT knockdown significantly enhanced cytotoxicity in Nalm-6 cells compared to individual interventions. This was characterized by the upregulation of ferroptosis promoters (lipid-ROS, Fe²⁺, ACSL4) and suppression of inhibitors (GSH, GPx, SLC7A11, GPx4). The response showed cell-line specificity, with Nalm-6 cells exhibiting enhanced ferroptotic sensitivity while REH cells underwent apoptotic cell death. Molecular docking revealed strong curcumin-protein interactions (∆G = -34.24 kcal/mol for hTERT). This study establishes hTERT as a critical regulator of ferroptotic cell death in pre-B ALL, operating through redox homeostasis, iron metabolism, and lipid peroxidation pathways. The cell-type-specific responses suggest promising therapeutic strategies through combined hTERT suppression and ferroptosis induction., Competing Interests: Declarations. Ethics approval and consent to participate: The study gained the approval of the ethical committee of the Kerman University of Medical Sciences with the Ethical approval code: IR.KMU.REC.1400.063. Written informed consent was obtained from all participants. All methods were performed following the relevant guidelines and regulations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

In this study an in situ forming gel for curcumin and piperine delivery is investigated as a long-lasting strategy in the local treatment of inflammatory and degenerative joint disease, such as osteoarthritis and rheumatoid arthritis. Particularly glyceryl monooleate, in association with phosphatidylcholine and ethanol, were employed. Different ratios between excipients were tested, with the aim to obtain a liquid form suitable for subcutaneous injection, gaining a semisolid consistency in contact with biological fluids. A formulative study was conducted to assess the composition impact on the structural properties of the formulations, particularly focusing on injectability and phase transition. Curcumin and piperine were loaded, singularly or jointly, in selected in situ forming gels. Structural characterization, performed by X-ray scattering, revealed disordered reverse micellar phases, undergoing transition to hexagonal and cubic Pn3m phase upon hydration. In vitro dialysis release study demonstrated a sustained release of both drugs over 96 h, with a faster release in the case of jointly loaded drugs. Mechanistic analysis and water uptake studies indicated a drug release governed by both diffusion and swelling/erosion of the lipid supramolecular structure. Furthermore, an ex vivo release analysis performed using human skin explants suggested the formulation suitability for subcutaneous injection, indicating that the presence of piperine in the in situ formed gel allowed to double the curcumin release with respect to the simple curcumin loaded gel., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Previous research indicates that Transforming growth factor beta-3 (TGFβ3) expression levels correlate with breast cancer metastasis, and elevated TGFβ3 levels have been linked with poor overall survival in breast cancer patients. The study used computational methods to examine curcumin's effects on TGFβ3, a chemical with antiviral and anticancer characteristics. The curcumin has low Molecular Weight 368.130 (MW) and follows Lipinski Rule, Pfizer Rule, GSK Rule, Golden Triangle, BMS Rule, zero PAINS alert and Acute Toxicity Rule with zero alert. Any drug-like contender must follow these qualities. Through molecular docking analyses, curcumin displayed favourable binding affinities at the TGFβ3 binding pocket, forming key interactions such as hydrogen bonds with residues like ASP323, ARG325, VAL333, HIS334, PRO336, LYS337, GLY393, and ARG394. 500 ns molecular dynamic simulations examined docking interactions. Molecular dynamics (MD) simulations trajectories analysis, by calculating lower structural deviation, minimal residual fluctuations, structural compactness assessment by calculating radius of gyration, surface area calculation which interact with solvent, role of hydrogen bonding, and secondary structural analyses. Furthermore, principal component, Gibbs free energy landscape and MMPBSA analysis, signifying system stability. These data suggest curcumin may inhibit TGFβ3, providing a framework for developing new compounds targeting this protein., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Gastric ulcer is a common disorder of the digestive system. The combination of turmeric and honey is known to treat stomach ulcers. However, curcumin, an active component in turmeric, has limitations, i.e., poor water solubility and low oral bioavailability. Therefore, turmeric and honey were formulated into a nanoemulsion with black pepper to enhance curcumin bioavailability. The study followed a systematic approach to optimize the nanoemulsion formula, determine stability, and evaluate ulcer healing activity in rats with ethanol-induced gastric ulcers. Nanoemulsion was prepared using a low-energy emulsification method called emulsion phase inversion (EPI). Two stability evaluations were carried out, i.e., storage and freeze-thaw stability tests. The organoleptic, droplet size, polydispersity index, pH, viscosity, and curcumin content of the nanoemulsion were evaluated. Male Wistar albino rats were induced with 96% ethanol for six days. The rats were divided into six groups, i.e., healthy control, ulcerated control, omeprazole, two different doses of turmeric, honey, and black pepper nanoemulsion (NTBH1 and NTBH2), and turmeric and honey nanoemulsion (NTH). The antiulcer activity was determined by measuring the ulcer area, ulcer index, curative index, ulcer severity score, and histology. The best formula with the smallest droplet size, i.e., 144.6±3.8 nm, was obtained from the nanoemulsion using Tween 80 as surfactant, glycerin as cosolvent, and sodium alginate as viscosity enhancer. The result showed that the nanoemulsion was stable after being stored at 25 and 40°C for four weeks and after six cycles of freeze-thaw test. The ulcer index of the ulcerated rats from the lowest to the highest, i.e., NTBH2, omeprazole, NTH, and NTBH1. In conclusion, the nanoemulsion developed in this study containing turmeric, honey, and black pepper holds promising potential in treating gastric ulcers, offering a hopeful outlook for future treatments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Adlia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

It is crucial to inhibit the neuroinflammation response as it is a prominent factor contributing to the pathogenesis of neurodegenerative disorders. However, the limited development of neuroinflammation models dramatically hinders the efficiency of nanomedicine discovery. In recent years, the optically transparent zebrafish model provided unique advantages for in vivo imaging of the whole body, allowing the progression of the disease to be visualized. In this study, a lipopolysaccharide (LPS)-mediated zebrafish neuroinflammation model was established to visualize the brain distribution and quickly evaluate the anti-inflammation effect of human ferritin-loaded curcumin (Cur@HFn) nanoparticles. The Cur@HFn drug delivery system was successfully prepared and characterized. The HFn nanocage demonstrated significant brain accumulation and prolonged circulation in a zebrafish larval model. In the LPS-induced zebrafish model, Cur@HFn significantly reduced neutrophil recruitment within the brain region of the LPS-treated zebrafish. Additionally, Cur@HFn mitigated nitric oxide (NO) release and downregulated the mRNA expression levels of proinflammatory cytokines, including TNF-α and IL-1β. Lastly, Cur@HFn significantly reduced the damage of raphe nucleus neurons and alleviated the locomotion deficiency caused by LPS. Overall, our findings highlight that Cur@HFn is a promising drug delivery system for the targeted treatment of brain disorders. This zebrafish neuroinflammation model could be used for high-throughput in vivo drug screening and discovery.

Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease characterized by the presence of numerous proinflammatory cytokines, massive reactive oxygen species (ROS) and excess lipids, which together result in an overall inflammatory positive feedback loop in the plaque focus. Due to its excellent enzyme-like activity in ROS scavenging and inflammation inhibition, as well as its photothermal effects in the lipid efflux ability of foam cells, Prussian blue (PB) has greater potential in preventing inflammatory factor loops for enhanced treatment of AS than traditional nanozymes. In this study, the multifunctional nanozyme BSA@PB/Cur was synthesized by self-assembly of bovine serum albumin (BSA) with PB and further encapsulation of the anti-inflammatory drug curcumin (Cur). The in vitro results showed that BSA@PB/Cur could effectively scavenge ROS and inhibit the expression of the inflammatory cytokines TNF-α and IL-1β as well as enhance the expression of ABCA1 and ABCG1 in foam cells, promote cholesterol efflux and inhibit foam cell formation. The in vivo experimental results demonstrated that BSA@PB/Cur could target plaque locations, significantly efflux the lipid content, and decrease the matrix metalloproteinase expression. This research provides a potential strategy for alleviating the persistent inflammatory feedback loop within the plaque microenvironment for AS treatment.

Curcumin, a compound known for its antioxidant and neuroprotective properties, faces challenges due to its low water solubility, which can limit its effectiveness. One effective method to address this issue is through amorphization. Incorporating curcumin into a polymeric matrix to form amorphous solid dispersions is a common approach. Another strategy involves co-amorphous systems, where low-molecular-weight components act as co-formers. A recent innovative approach combines these strategies. This study used tryptophan as a co-former and prepared systems using supercritical fluid technology. The amorphous nature of two systems was confirmed through X-ray powder diffraction: one with 10% curcumin and a polymer, and another with 10% curcumin, a polymer, and tryptophan. Fourier-transform infrared analysis demonstrated molecular interactions among all components in the systems. Scanning electron microscopy revealed that the amorphization process significantly modified the morphology of the powder particles. The ternary system with tryptophan notably increased curcumin solubility by over 300-fold. The amorphous form of curcumin in both systems exhibited significantly higher dissolution rates compared to its crystalline form. The system with tryptophan showed more than a threefold improvement in permeability according to the PAMPA test. The enhanced solubility led to over a sixfold increase in antioxidant activity and a 25-fold improvement in the inhibition of the enzyme butyrylcholinesterase.

A zwitterionic, stimuli-responsive liposomal system was meticulously designed for the precise and controlled delivery of curcumin, leveraging enzyme-specific and hyperthermic stimuli to enhance therapeutic outcomes. This platform is specifically engineered to release curcumin in response to phospholipase A2 , an enzyme that degrades phospholipids, enabling highly targeted and site-specific drug release. Mild hyperthermia (40 °C) further enhances membrane permeability and activates thermosensitive carriers, optimizing drug delivery. Curcumin encapsulation is facilitated through a combination of zwitterionic and electrostatic interactions, significantly improving both loading capacity and encapsulation efficiency. A design of experiments (DoE) approach was employed to systematically optimize lipid-to-cholesterol ratios and formulation conditions. The liposomal system was thoroughly characterized using dynamic light scattering, zeta potential measurements, and transmission electron microscopy, ensuring stability and structural integrity. Notably, this system effectively encapsulates hydrophobic curcumin while maintaining particle size and bioactivity. In vitro studies revealed robust antioxidant and anti-ROS activities, alongside excellent biocompatibility, with no cytotoxicity observed at concentrations up to 2000 μg/mL. Furthermore, the zwitterionic liposomes enhanced M2 macrophage polarization and reduced oxidative stress. This advanced platform offers a promising, biocompatible solution for targeted curcumin delivery.

Cholangiocarcinoma (CCA) or bile-duct cancer is most prevalent in Southeast Asian counties including Thailand. Patients present at an advanced stage when the cancer is often drug resistant, leading to chemotherapy failure. Curcumin has therapeutic potential with various anticancer properties. However, its effectiveness is limited by its low bioavailability, poor solubility, and instability. This study aimed to synthesize, characterize and evaluate the efficacy of curcumin-loaded maltodextrin-based proniosomes (CMPNs) to overcome the limitations of curcumin for treating gemcitabine-resistant CCA cells (KKU-213B GemR ) in vitro and in vivo . Various proniosome formulations were developed and tested for their efficacy against KKU-213B GemR cells using cytotoxicity, clonogenic, migration, and invasion assays. The potential mechanism involving in cell cycle arrest, apoptosis, expression of C/EBP homologous protein (CHOP), a pro-apoptotic transcription factor, and other apoptotic markers were investigated. The results showed that nanoscale CMPNs exhibited a good curcumin loading capacity and an entrapment efficiency of over 97%, as well as good stability and permeability through porcine esophageal mucosa. CMPNs inhibited proliferation, colony formation, migration/invasion and induced apoptosis in KKU-213B GemR cells. Western blot analysis revealed CMPNs significantly increased CHOP, the cleavage products of poly(ADP-ribose) polymerase-1 (PARP-1), apoptosis-inducing factor, and caspase-3 expression in KKU-213B GemR cells. A xenograft model revealed that 62.5 mg/kg BW CMPNs significantly suppressed proliferating cell nuclear antigen and increased CHOP-mediated apoptosis, leading to significantly reduced tumor volume. In conclusion, CMPNs effectively overcome limitations of curcumin and offer an effective strategy against gemcitabine-resistant CCA via CHOP-mediated pathways. These proniosomes are promising as an alternative treatment approach for CCA.

Widespread exposure to endocrine disruptors is associated with metabolic dysfunction and reproductive toxicity. Tetrahydrocurcumin (THC) has attracted attention as it offers protection against obesity and metabolic disorders due to its potent antioxidative and diverse biological properties but its influence and underlying mechanism of action on adipose tissue function and DEHP-induced testicular injury remain unknown. Our results showed that THC (100 mg kg -1 day -1 ) administration for 27 weeks enlarged adipocytes while attenuating macrophage infiltration and IL-6 expression in the adipose tissue of male C57BL/6J mice exposed to 5 mg kg -1 day -1 of DEHP. Moreover, THC ameliorated DEHP-induced deregulation of adiponectin but not leptin. DEHP caused testicular histological damage, spermatogenesis impairment, apoptosis, inflammation, and AGE, which were improved by THC. THC treatment elevated Nrf2/HO-1 and decreased Glut1 in interstitial Leydig cells, which may contribute to its beneficial effects on the testis. Our results further demonstrated that THC also ameliorated circulating adiponectin and testicular adipoR1-AMPK signaling, partially accounting for the improvement of DEHP-caused testicular dysfunction. The finding of this study revealed that THC is a promising candidate for improving adipose and testicular dysfunction caused by DEHP.

Background: Knee osteoarthritis (OA) is a common and debilitating disorder marked by joint degradation, inflammation, and persistent pain. This study examined the possible therapeutic effects of curcumin and vitamin D on OA progression and pain in a rat knee OA model by anterior cruciate ligament transection and meniscectomy (ACLT + MMx). Methods: Male Wistar rats were categorized into five groups: control, curcumin-treated (100 mg/kg/day), vitamin D-treated (25 µg/kg/day), a combination of vitamin D and curcumin, and sham-operated. All supplements were administered orally on a daily basis for 12 weeks. Pain behaviors were assessed, serum biomarkers were measured, and knee histology was examined. Results: Both curcumin and vitamin D independently reduced pain, while the combined group exhibited better analgesic effects. Serum inflammatory cytokines demonstrated a decrease in pro-inflammatory cytokines and an elevation in anti-inflammatory cytokine interleukin-10 (IL-10) in the supplement groups. The antioxidative markers were partially recovered by curcumin and vitamin D supplement. However, the oxidative stress marker Cartilage Oligomeric Matrix Protein (COMP) was significantly reduced. Histology analysis revealed a preservation of joint architecture and cartilage integrity and decreased synovium inflammation in the groups treated with curcumin and vitamin D. Conclusions: Our findings indicate a dual mechanism that encompasses the role of anti-inflammation and antioxidation on knee OA progression and pain reduction, underscoring the potential of these natural chemicals as therapeutic agents for knee OA; curcumin and vitamin D supplement may be added in delaying knee OA progression and associated pain management in clinical patient care.

A major challenging problem facing effective ovarian cancer therapy is cisplatin resistance. Re-sensitization of cisplatin-resistant ovarian cancer cells to cisplatin (CDDP) has become a critical issue. Curcumin (CUR), the most abundant dietary polyphenolic curcuminoids derived from turmeric ( Curcuma longa ), has achieved previously significant anti-cancer effects against human ovarian adenocarcinoma SKOV-3/CDDP cisplatin-resistant cells by inhibition the gene expression of the antioxidant enzymes ( SOD1 , SOD2 , GPX1 , CAT and HO1 ), transcription factor NFE2L2 and signaling pathway ( PIK3CA / AKT1 / MTOR ). However, the detailed mechanisms of curcumin-mediated re-sensitization to cisplatin in SKOV-3/CDDP cells still need further exploration. Here, a suggested curcumin pre-treatment therapeutic strategy has been evaluated to effectively overcome cisplatin-resistant ovarian cancer SKOV-3/CDDP and to improve our understanding of the mechanisms behind cisplatin resistance. The findings of the present study suggest that the curcumin pre-treatment significantly exhibited cytotoxic effects and inhibited the proliferation of the SKOV-3/CDDP cell line compared to the simultaneous addition of drugs. Precisely, apoptosis induced by curcumin pre-treatment in SKOV-3/CDDP cells is mediated by mitochondrial apoptotic pathway (cleaved caspases 9, 3 and cleaved PARP) activation as well as by inhibition of thioredoxin reductase (TRXR1) and mTOR/STAT3 signaling pathway. This current study could deepen our understanding of the anticancer mechanism of CUR pre-treatment, which not only facilitates the re-sensitization of ovarian cancer cells to cisplatin but may lead to the development of targeted and effective therapeutics to eradicate SKOV-3/CDDP cancer cells.

Chemoprevention is one of the accessible strategies for preventing, delaying or reversing cancer processing utilizing chemical intervention of carcinogenesis. NAD(P)H quinone oxidoreductase 1 (NQO1) is a xenobiotic metabolizing cytosolic enzyme/protein with important functional properties towards oxidation stress, supporting its ability in detoxification/chemoprotective role. A set of 3,5-diylidene-4-piperidones (as curcumin mimics) bearing alkyl sulfonyl group were synthesized with potential NQO1 induction properties. Compounds 5ab (R = 2-MeOC 6 H 4 , R' = Me) and 5ac (R = 2-MeOC 6 H 4 , R' = Et) are the most promising agents synthesized (% induction of NQO1 = 51.562, 45.793) relative to that of 4'-bromoflavone (4'-BF, reference standard) at 10 µM. LPS-induced iNOS production in RAW264.7 macrophages of the most promising agents discovered (5ab and 5ac) displayed concentration-dependent with comparable activities to the reference anti-inflammatory drug indomethacin. Molecular modeling studies (including QSAR, molecular docking and molecular dynamics) were accessed supporting the observed biological profiles., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Epigenetic abnormalities play a critical role in colon carcinogenesis, making them a promising target for therapeutic interventions. In this study, we demonstrated that curcumin reduces colon cancer cell survival and that a decrease in lysine methylation was involved in such an effect. This correlated with the downregulation of methyltransferases EZH2, MLL1, and G9a, in both wild-type p53 (wtp53) HCT116 cells and mutant p53 (mutp53) SW480 cells, as well as SET7/9 specifically in wtp53 HCT116 cells. The effects induced by curcumin were more pronounced in wtp53 cells, where it induced a stronger apoptosis and ferroptosis. Interestingly, curcumin also reduced mutp53 expression, suggesting that it could enhance the efficacy of other therapies, particularly in overcoming drug resistance mechanisms associated with mutp53. For instance, in this study, we show that curcumin sensitized SW480 cells to SET7/9 inhibition by sinefungin, further supporting its potential as a combinatorial therapeutic agent. However, although to a lesser extent, curcumin also impaired cell survival in HCT 116 p53 null cells, suggesting that other molecular pathways or factors, beyond p53, may be involved in curcumin-induced cytotoxicity.

In order to solve the problem of poor adhesion of polysaccharide coatings in meat storage and inconvenient secondary spraying, which leads to poor preservation effect, this study was inspired by the property of mussels to adhere firmly to surfaces and design a bioactive composite coating. Here, curcumin-loaded zein nanoparticles (CZ NPs) were successfully prepared and incorporated into carrageenan-based biocomposite coatings for chilled meat preservation. The prepared curcumin-zein-riboflavin-carrageenan (CZRC) coating featured smooth spherical morphology and the solubility of hydrophobic substances, the adhesion and stability of the composite coating were respectively improved to 3.8 and 6 times compared to CZ NPs. The CZRC coating also shows desirable antioxidant activity (89.78 ± 4.8 % on DPPH and 91.40 ± 2.1 % on ABTS+) and the treatment based on CZRC coating under light irradiation reduced Pseudomonas fragi (by 2.02 log CFU/mL) and Brochothrix thermosphacta (by 4.35 log CFU/mL), which prolonged the shelf life of lamb and pork to 1.8 and 2.3 times at 4 °C storage condition. This work provides a viable strategy for the development of highly adhesive coatings with self-activation enhanced activity to achieve long-lasting preservation., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication. I would like to declare on behalf of my coauthors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aimed to investigate how hyaluronic acid interfacial decoration affects the stability, cellular absorption, and anti-inflammatory effects of curcumin-loaded nanostructured lipid carriers. Nanocarriers were synthesized with an ovalbumin single layer and ovalbumin/hyaluronic acid double, mixed, or conjugated layers. All nanocarriers were spherical (200-300 nm diameter), and their encapsulation efficiency exceeded 95 %. Among the layers, the conjugated one exhibited the highest elastic surface dilatational modulus of approximately 40 mN/m, and the longest curcumin half-life of 186.07 days at 4 °C. Spearman's correlation analysis showed a negative correlation (r = -0.6698) between the recrystallization index and curcumin stability. The layer's mechanical strength improved curcumin stability by preventing crystal transition. Hyaluronic acid decoration enhanced the curcumin uptake of Caco-2 cells by 1.96-2.48 folds. Among the layers, the conjugate one was the most effective because of its strong binding constant with the receptor. Hyaluronic acid decoration improved the anti-inflammatory effects of curcumin., Competing Interests: Declaration of competing interest The authors state that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The ideal smart food-packaging film exhibits responsive color warnings and antimicrobial properties when food metamorphism starts. However, in practical applications, these film responses are slow, usually taking several days, which is not conducive to effective antimicrobial effects. In this study, natural plant-derived curcumin was introduced into waterborne polyurethane (WPU) dispersions through two modes: free-state and end-capping. During the film-forming process, under the influence of surface tension, the capped-end curcumin migrated to the surface and further immobilized free curcumin through π-π interactions. Consequently, curcumin accumulated on the film surface, preventing flipping in moist or hydrophobic environments, in addition to acting as a color indicator for the rapid detection of crab spoilage, thus generating ammonia for a real-time response (of approximately 60 s). Simultaneously, the curcumin degraded, producing water-soluble antimicrobial curcumin-degradation products. This study significantly advances the practical application of curcumin in smart food packaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Curcumin is widely known for its antioxidant and anti-inflammatory properties, but its mechanism of action in mitigating oxidative stress injury in brain vascular endothelial cells remains unclear. Due to the poor bioavailability of curcumin, it is challenging to achieve effective concentrations at the target sites. Nano-micelles are known for their ability to improve the solubility, stability, and bioavailability of hydrophobic compounds like curcumin. This study investigated the effects and mechanisms of free curcumin and curcumin embedded in nano-micelles (M(Cur)) on oxidative stress-induced injury in bEnd.3 cells., Results: At a protective concentration of 10 μg mL -1 , micellar curcumin was better able to recover the morphology of bEnd.3 cells under oxidative stress while increasing cell viability, restoring mitochondrial membrane electrical potential, and effectively inhibiting reactive oxygen species generation with a positive cell rate of 2.21%. These results indicate that curcumin significantly improves H 2 O 2 -induced oxidative stress damage in endothelial cells by maintaining the cellular antioxidant balance., Conclusion: This study adds to knowledge regarding the role of nano-micelles in curcumin intervention for endothelial cell oxidative damage and provides insights for the development of curcumin-based dietary supplements. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Biomass-based composite packaging materials loaded with functional fillers have good application prospects in food preservation and freshness detection. Self-healing hydrogel packaging films based on nanocellulose (CNF), polyvinyl alcohol (PVA), and ZIF-8 embedded with curcumin (Cur@ZIF-8) were developed in this study. The synthesis of Cur@ZIF-8 was demonstrated by characterization experiments. The addition of Cur@ZIF-8 enhanced the water vapor barrier property, tensile strength, and elongation at break of hydrogel films by 49.2 %, 193.5 %, and 172.9 %, respectively, and endowed them with excellent antimicrobial, antioxidant, and ammonia sensitivity. In packaging tests with fish, hydrogel films loaded with Cur@ZIF-8 inhibited spoilage and microbial growth to extend the shelf life of fish to 9 days, and the color change of hydrogel films allowed for real-time monitoring of fish freshness. This study provided a new solution for smart packaging materials with dual functions of preservation and freshness indication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Curcumin is known for its potential health benefits; however, the evidence remains inconclusive regarding its necessity as a supplement for athletes during the preparatory phase of training. This study aimed to assess the effect of 6-week curcumin supplementation at a dose of 2g/day on selected inflammatory markers, blood count, and brain-derived neurotropic factor (BDNF) levels in middle-aged amateur long-distance runners during the preparatory period of a macrocycle. Thirty runners were randomly assigned to either a curcumin-supplemented group (CUR, n = 15) or a placebo group (PLA, n = 15). Venous blood samples were collected at rest, immediately post-exercise, and 1h post-exercise. The participants underwent a graded exercise stress test, with an increasing inclination angle after reaching a speed of 14 km/h, both before and after the 6-week supplementation period. Blood samples were collected at rest, 3 minutes post-stress test, and after 1 hour of recovery. The results showed no significant changes in C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-1 β (IL-1β), or blood morphology due to curcumin supplementation. However, BDNF levels increased by 21% in the CUR group post-supplementation, while a 5% decrease was observed in the PLA group. These findings do not support a significant effect of curcumin supplementation on inflammatory markers, blood count, or BDNF concentration. Further research is warranted to determine the potential benefits of curcumin supplementation for endurance athletes during the preparatory period for a training cycle., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Bańkowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Orally targeting nanostrategies of multiple nutraceuticals have attracted increasing attention in ulcerative colitis (UC) therapy for superior patient compliance, cost-effectiveness, and biocompatibility. However, the actual targeting delivery and bioefficacy of nutraceuticals are extremely restricted by their poor solubility, interior gastrointestinal retention, and base permeability. Herein, we developed controllable colon-targeting nanoparticles (NPs) composed of a quaternary ammonium chitosan (HTCC) shell and succinic acid-modified γ-cyclodextrin (SACD) core for precise UC treatment. Egg white-derived peptides (EWDP, typical food-derived peptides) could not only function as potential cross-linkers to induce the differential coassembly with the above biopolymers but also aid the hydrophobic curcumin (Cur) solubility as well as nutrition enhancers for oral synergism of colitis therapy. More specifically, NPs with higher EWDP coassembly efficiency exhibited better pH-sensitive colloidal tunability (e.g., smaller size, higher rigidity, and roughness) and robust nutraceuticals (EWDP/Cur) coloading capacity (24.0-33.2% ≫ 10%, pH 2.0-7.0). Compared with pure nutraceuticals, NPs exhibited excellent cellular absorption (almost 10 times) and oral bioavailability (4.19-5.05 times) enhancement via faster mucus permeation and macropinocytosis transport, indirectly regulating the systemic inflammatory response. The sustainable sequential release and targeted accumulation profiles of NPs directly facilitated the interactions with the colonic microenvironment, verified by the intestinal barrier recovery and gut microbiota restoration. Moreover, the critical role of amino acid metabolism reconfirmed the importance of EWDP coassembly efficiency in maintaining intestinal homeostasis. Overall, this study would provide a facile, quantitative, and versatile perspective into the programmable design of food-derived peptide (e.g., EWDP) coassembled nanoplatforms for oral targeted therapy of UC.

Although curcumin is a well-known natural polyphenol with many biological activities, its clinical application has been limited by low aqueous solubility and stability. Therefore, curcumin derivatives have been proposed to overcome these limitations and increase anticancer activity. This study tested curcumin derivatives with modified feruloyl moieties ( 2a and 2a-B ) and the β-diketo moiety ( 2a-B ) to better understand their anticancer mechanism against human bladder cancer cells. The anticancer activity of 2a and 2a-B was determined using MTT (hypoxic conditions) and LDH (normoxic conditions) assays. An ELISA-based protein panel was used to find the potential molecular targets, while flow cytometric, colorimetric, fluorescent, and luminescent assays were used to investigate the cell death mechanism. It was shown that compound 2a exerted a more potent cytotoxic effect under hypoxic conditions, while compound 2a-B demonstrated a comparable effect in normoxic and hypoxic conditions. The potential molecular targets modified by 2a and 2a-B depending on oxygen concentration were also proposed. Both compounds alter cell cycle progression by blocking the cell cycle in the G2/M phase and decreasing the percentage of cells in the G0/G1 phase. Compound 2a-B led to phosphatidylserine translocation, increased caspase 3/7 activity, and decreased mitochondrial membrane potential, suggesting a mitochondrial apoptosis pathway. We found that the Akt signaling pathway may modulate the activity of compound 2a-B , as evidenced by enhanced cytotoxic activity in combination with MK-2206, an Akt 1/2/3 inhibitor. Thus, our results provide new insights into the anticancer activity of compounds 2a and 2a-B ; however, further studies are needed to better understand their therapeutic potential.

The simultaneous administration of multiple drugs within identical nanocarriers to cancer cells or tissues can result in the effective action of drugs at reduced concentrations. In this investigation, PAMAM dendrimers (G4-PAMAM) were employed to link with methotrexate (MTX) using DCC/NHS chemistry and followed by the entrapment of curcumin (Cur) within it. The establishment of covalent bonds between MTX and the PAMAM dendrimer led to PAMAM-MTX interaction, verified and described through FT-IR. Various techniques were employed to evaluate the structural properties of the prepared Cur-PAMAM-MTX NC. The Cur-PAMAM-MTX NC, after preparation, exhibited a particle size of 249 nm, with an encapsulation efficiency (EE) of ~ 81% for Cur. The cumulative in vitro release of Cur-loaded NC indicated a controlled release influenced by time and pH. The cell study results revealed that Cur-PAMAM-MTX NC exhibited significantly higher cytotoxicity than free MTX, Cur, and other formulations tested in vitro. The synergistic effect of co-delivery of MTX and Cur by PAMAM significantly increased cytotoxicity. Besides, the significant ROS level rising has been shown in the treated cells with MTX-PAMAM-Cur. Considering these findings, the co-delivery NC shows promise for additional in vitro investigations and possesses the capacity to function as an effective framework for the combined delivery of MTX and Cur in cervical cancer chemotherapy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The etiology of hyperlipidemia is complex, and our understanding of its underlying mechanisms is limited. Effective therapeutic strategies for hyperlipidemia remain elusive. This study aimed to confirm the effect of curcumin on hyperlipidemia treatment and elucidate the precise mechanism. A high-fat diet-induced hyperlipidemia model using C57BL/6J mice and HaCaT cells was established. Co-immunoprecipitation and immunofluorescence were performed to detect protein interactions, and immunoprecipitation coupled with Western blotting was used to assess protein succinylation. 40 μM of curcumin administration promoted cell viability, increased the levels of glutathione peroxidase, glutathione, catalase, and superoxide dismutase, while reducing reactive oxygen species activity and the levels of triglycerides and malondialdehyde. Additionally, curcumin attenuated the development of hyperlipidemia in vivo. Mechanistically, 100 mg/kg of curcumin promoted O-GlcNAcylation and increased the expression of O-linked N-acetylglucosamine transferase in HaCaT cells. Furthermore, apolipoprotein C3 was identified as a substrate of O-linked N-acetylglucosamine transferase, and O-GlcNAcylation of apolipoprotein C3 enhanced its stability. Rescue experiments further verified that curcumin exerts its effects by regulating apolipoprotein C3 expression. In conclusion, these findings provide novel insights into the treatment of hyperlipidemia., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mitochondria produces energy through oxidative phosphorylation (OXPHOS), maintaining calcium homeostasis, survival/death cell signaling mechanisms, and redox balance. These mitochondrial functions are especially critical for neurons. The hippocampus is crucial for memory formation in the brain, which is a process with high mitochondrial function demand. Loss of hippocampal function in aging is related to neuronal damage, where mitochondrial impairment is critical. Synaptic and mitochondrial dysfunction are early events in aging; both are regulated reciprocally and contribute to age-associated memory loss together. We previously showed that prolonged treatment with Curcumin or Mitoquinone (MitoQ) improves mitochondrial functions in aged mice, exerting similar neuroprotective effects. Curcumin has been described as an anti-inflammatory and antioxidant compound, and MitoQ is a potent antioxidant directly targeting mitochondria; however, whether Curcumin exerts a direct impact on the mitochondria is unclear. In this work, we study whether Curcumin could have a mechanism similar to MitoQ targeting the mitochondria. We utilized hippocampal slices of 4-6-month-old C57BL6 mice to assess the cellular changes induced by acute Curcumin treatment ex-vivo compared to MitoQ. Our results strongly suggest that both compounds improve the synaptic structure, oxidative state, and energy production in the hippocampus. Nevertheless, Curcumin and MitoQ modify mitochondrial function differently; MitoQ improves the mitochondrial bioenergetics state, reducing ROS production and increasing ATP generation. In contrast, Curcumin reduces mitochondrial calcium levels and prevents calcium overload related to mitochondrial swelling. Thus, Curcumin is described as a new regulator of mitochondrial calcium homeostasis and could be used in pathological events involving calcium deregulation and excitotoxicity, such as aging and neurodegenerative diseases., Competing Interests: Declarations. Ethics Approval: Experimental procedures were approved by the Bioethical and Biosafety Committee of the University San Sebastian, Chile; FONDECYT 11170546. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Following prolonged exposure to hypoxic conditions, for example, due to ascent to high altitude, aging or stroke, cognitive deficits can develop. The exact nature and genesis of hypoxia-induced cognitive deficits remain unresolved. Curcumin has been reported to stimulate neurogenesis and reduce neuronal degeneration. This study aimed to investigate the effect of curcumin on cognitive deficits in hypoxic-brain injury mice and its potential mechanism. Eight-week-old male C57BL/6J mice were exposure to normobaric-hypoxia (13%O 2 ) 14 days to establish hypoxic-brain injury models. Morris water maze and novel object recognition were used to detect the cognitive function of each mouse. Immunofluorescence assays, including Fluoro-Jade C (FJC) and bromodeoxyuridine (BrdU), were used to detect neuronal degeneration and neurogenesis. Thy1-YFP transgenic mice were used to detect synapse plasticity. Our results showed that curcumin administration rescued the impaired cognition of mice, shown as enhanced BrdU + and dendritic spine in hippocampus. At the molecular level, curcumin was found to promote the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95). The results of primary hippocampal neuron detection showed that curcumin could promote dendritic growth. In conclusion, our study indicates that curcumin, increased BDNF and PSD95 expression and contacted with interneurons, salvaged of interneurons may normalize ambient neuroplasticity, resulting in the preservation of neurogenesis processes as well as contributing to improve cognitive performance., Competing Interests: Declarations. Compliance with ethical standards: All animal experiments fully complied with the related laboratory animal regulations (No.2023EC-KY-009), and conducted in accordance with ethical requirements and ARRIVE guidelines. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Non-tuberculous mycobacterial skin infection lead to complex and lengthy treatment cycles. Antimicrobial photodynamic therapy (aPDT) is an emerging promising approach for treating infections. This study aims to assess the effects of aPDT using curcumin as a photosensitizer (PS) on non-tuberculous mycobacteria, Mycobacterium abscessus, a subtype that has become common in dermatology in recent years. The antimicrobial efficacy of curcumin-mediated aPDT against M.abscessus ATCC19977 was evaluated using the colony-forming unit (CFU) assay. Reactive oxygen species (ROS) production and cell membrane integrity were assessed using H 2 DCFDA and propidium iodide staining, respectively. Cellular damage was further examined through transmission electron microscopy (TEM). Curcumin-mediated aPDT showed significant antimicrobial effects on M.abscessus in a concentration- and light-dose-dependent manner. Complete inactivation of M.abscessus was achieved with 100 μM curcumin and 48 J cm - 2 light exposure. ROS levels and cell membrane damage increased with higher curcumin concentrations, with fluorescence intensities of ROS and damaged cells increasing by 5.32 and 9.53 times, respectively, compared to untreated controls. TEM confirmed extensive cell wall and cytoplasmic damage in treated cells. This study demonstrates that M.abscessus could be effectively inactivated by curcumin in the presence of light. Therefore, curcumin-mediated aPDT shows promise as a treatment for M.abscessus., Competing Interests: Declarations. Conflict of interest: Authors have no conflict of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Alcoholic liver disease (ALD) is a chronic toxic liver injury caused by long-term heavy drinking. Due to the increasing incidence, ALD is becoming one of important medical tasks. Many studies have shown that the main mechanism of liver damage caused by large amounts of alcohol may be related to antioxidant stress. As an important antioxidant, cysteine (Cys) is involved in maintaining the normal redox balance and detoxifying metabolic function of the liver, which may be closely related to the pathogenesis of ALD. Therefore, it is necessary to develop a simple non-invasive method for rapid monitoring of Cys in liver. Thus, a near-infrared (NIR) fluorescent probe DCI-Ac-Cys which undergoes Cys triggered cascade reaction to form coumarin fluorophore is developed. Using the DCI-Ac-Cys, decreased Cys was observed in the liver of ALD mice. Importantly, different levels of Cys were monitored in the livers of ALD mice taking silybin and curcumin with the antioxidant effects, indicating the excellent therapeutic effect on ALD. This study provides the important references for the accurate diagnosis of ALD and the pharmacodynamic evaluation of silybin and curcumin in the treatment of ALD, and support new ideas for the pathogenesis of ALD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osteosarcoma (OSA) is a bone cancer that affects both humans and animals, with dogs being particularly vulnerable. Standard therapy is often limited by multidrug resistance (MDR), primarily due to the overexpression of P-glycoprotein (P-gp), which expels drugs from the cells, reducing their efficacy. To overcome this challenge, drug delivery systems (DDS) and P-gp modulators have been explored. However, developing DDS that selectively target cancer cells remains difficult, with many current options lacking efficiency. Our research group has recently developed an innovative type of nanoparticle with a lipid core and a calcium phosphate shell (CaP-NPs), which enhances the uptake of doxorubicin (DOXO) in OSA cells. In this study, we loaded a lipophilic ester of doxorubicin (C12DOXO) and curcumin (CURC), a natural P-gp modulator, into CaP-NPs and co-incubated them into human and canine OSA cell lines, including DOXO-resistant cells. The results demonstrated a significant reduction in viability in human OSA cells. Additionally, the combination treatment led to a further increase in C12DOXO retention when cells were also treated with the P-gp inhibitor verapamil, indicating enhanced efficacy against MDR mechanisms. Notably, canine OSA cells exhibited a distinct response pattern, suggesting the presence of species-specific differences that warrant further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Abnormal activation or dysfunction of memory helper T (mTh) cells is closely associated with the development of ulcerative colitis (UC). Curcumin (Cur), the main component of turmeric, plays a critical role in the treatment of UC due to its favorable anti-inflammatory and immunomodulatory bioactivities. However, whether Cur modulates mTh7 cells to alleviate UC is unknown. In the present study, dextran sulphate sodium (DSS) was administered to establish a colitis model in mice. Our current findings indicated that Cur effectively ameliorated the manifestations of colitis in mice, and had a significant effect in reducing disease activity index (DAI), as well as in the colonic weight and the proportion of colonic weight to colonic length. While Cur reduced the pathological injuries of the colon, restore the length of the colon, inhibited the secretion of IL-7 and IL-21, restored the secretion of IL-2, IL-4, and IL-10. Furthermore, Cur had a regulatory effect on mTh7 cells and their subpopulation status. The results of molecular docking simulations and Surface Plasmon Resonance (SPR) indicated that Cur demonstrates strong interaction capabilities with both IL-7 and IL-7R and reduced the expression levels of IL-7/IL-7R mRNA and protein. It is suggested that the alleviation of DSS-induced colitis by Cur may be achieved by reducing the level of mTh7 cells and inhibiting the activation of IL-7/IL-7R signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Melanoma has emerged as a significant threat to human life and health. Microneedle (MN)-mediated transdermal drug delivery (TDD) has garnered attention in melanoma treatment for bypassing the first-pass effect. However, the propensity of melanoma to metastasize presents substantial challenges for MN mediated local treatment. Developing systemic therapies, such as immunotherapy in combination with TDD, is crucial for achieving effective melanoma treatment. Herein, a polyvinyl alcohol (PVA) MN-mediated multifunctional TDD system, designated MN@PDA@1-MT/CUR/DOX@HA (MN@PMCDH), was developed for synergetic chemotherapy/photothermal/immunotherapy of melanoma. PMCDH nanomedicines penetrate deep skin layers through MNs, accumulate at tumor sites guided by hyaluronic acid (HA), and selectively release drugs in response to the acidic tumor microenvironment and near-infrared (NIR) stimulation. Released curcumin (CUR) significantly enhances the efficacy of photothermal therapy (PTT) and chemotherapy, as well as improves the induction of immunogenic cell death (ICD) by increasing melanoma sensitivity to polydopamine (PDA)-mediated photothermal effects and doxorubicin (DOX). Moreover, the incorporation of 1-methyltryptophan (1-MT) to reverse the tumor immunosuppressive microenvironment can further enhance the effects of immunotherapy. In vitro studies revealed that the MN@PMCDH system can effectively induce ICD and inhibit tumor cell growth. Additionally, remarkable deep tumor cell inhibition effects are also achieved in 3D tumor models., (© 2024 Wiley-VCH GmbH.)

Cancers still globally endanger millions of people yearly; the incidences/mortalities of colorectal cancers are particularly increasing. The natural nanoparticles (NPs) and marine biopolymers were anticipated to provide effectual safe significances for managing cancers. The transformation of curcumin to nano-curcumin (NCur) was conducted with gum Arabic. The resulted NCur was utilized for the biosynthesis of selenium NPs (SeNPs), then bioactive nanocomposites (NC) from them with fucoidan (Fu) were fabricated and evaluated as candidates to suppress colorectal cancers (CaCo-2 and HT-29) cells. The NCur and NCur-synthesized SeNPs were effectually produced with mean diameters of 34.67 ± 4.32 and 5.17 ± 1.06 nm, respectively. The plain and NCs of Fu/NCur/SeNPs characterization, with infrared spectroscopy and electron microscopy, emphasized their interaction and conjugations. The entire agents/NCs had potent cytotoxic effects against cancers' lines; the NC of Fu/NCur/SeNPs was the most effectual with IC50 of 10.35 ± 0.83 and 19.44 ± 1.39 mg/L against CaCo-2 and HT-29 cells, respectively, which were significantly exceeded the action of standard cisplatin drug. The NCs led to vigorous DNA damages in CaCo-2 cancerous cells, as proved with comet assay. The ultrastructure imagining (scanning/transmission microscopy) of treated cells with Fu/NCur/SeNPs confirmed the capability of NCs to induce severe apoptosis and deformation signs in cancerous cells. The bio-based constituents of Fu/NCur/SeNPs and advocate their prospective applications for preventing/managing colorectal adenocarcinoma., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Curcumin, a compound from Curcuma longa L., has significant anti-inflammatory properties. However, the mechanisms underlying its anti-inflammatory activity in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) remain inadequately understood. This study aimed to further elucidate the molecular mechanisms of curcumin DSS-induced UC mice. Our data showed that curcumin alleviated DSS-induced colitis by reducing intestinal damage and inflammation, increasing goblet cells in colon tissues. Enzyme-linked immunosorbent assay revealed that curcumin reduced the expression of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1β, and interleukin-8) in serum and myeloperoxidase in colon tissues. A comprehensive analysis integrating network pharmacology and RNA sequencing (RNA-seq) revealed significant enrichment of the nuclear factor kappa B (NF-κB) signaling pathways. Notably, RNA-seq analysis demonstrated that curcumin significantly downregulated the mRNA expression of sphingosine kinase 1 (SphK1). Furthermore, molecular docking analysis showed that curcumin can bind to SphK1 and NF-κB. Additionally, curcumin was found to inhibit the activation of the SphK1/NF-κB signaling pathway in DSS-induced UC colon tissue. This study addresses pharmacologic and mechanistic perspectives of curcumin that ameliorates DSS-induced UC and inflammatory response., (© 2025 International Union of Biochemistry and Molecular Biology.)

Ischemic stroke (IS) often causes fearful sequela, even death. Curcumin was beneficial to IS, but its underlying molecular mechanism is unclear. Mice were subjected to middle cerebral artery occlusion (MCAO) surgery, and BV-2 cells were treated with oxygen-glucose deprivation/reoxygenation (OGD/R) induction to establish IS models in vivo and in vitro. Abundance of genes and proteins was determined using quantitative real-time polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and western blot. Interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Modified neurological severity score (mNSS), corner test, foot fault test, adhesive removal test, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were applied to evaluate the brain injury of mice. The correlation between miR-205-5p and Kruppel-like factor 2 (KLF2) was affirmed using dual luciferase reporter assay. Our results revealed that curcumin alleviated brain damage in MCAO mice through driving microglia M2 polarization. Of note, curcumin resulted in decreased miR-205-5p expression in MCAO mice. miR-205-5p knockdown resulted in promoted microglia M2 polarization in OGD/R conditions and achieved similar results to curcumin treatment in MCAO mice. Moreover, curcumin played a promoting role in microglia M2 polarization under OGD/R conditions, while miR-205-5p overexpression or KLF2 knockdown abolished these effects. On the mechanism, miR-205-5p was a target of curcumin, and miR-205-5p further interacted with KLF2 to inhibit activating transcription factor 2 (ATF2) expression. miR-205-5p, decreased by curcumin, suppressed microglia M2 polarization to worsen IS injury through the mediating KLF2/ATF2 axis., (© 2025 John Wiley & Sons Ltd.)

Photodynamic inactivation (PDI) is a new and promising strategy for eliminating foodborne pathogenic bacteria in food preservation, reducing associated health risks for consumers. This study aimed to develop an innovative PDI-based system to inactivate Salmonella Enteritidis PT4 on eggshells. The system includes 405 nm light-emitting diodes (LEDs) and the application of curcumin or carvacrol as photosensitizers. The antibacterial activity of the system was investigated in eggshells inoculated with S. Enteritidis PT4 at different temperatures (4, 25, and 37°C) and exposure times (15, 30, and 45 min). Carvacrol + LEDs application was completely inhibited S. Enteritdis PT4 at 4 (after 30 min), 25, and 37°C at the 45th min. Curcumin + LED completely inhibited bacterial growth after 45 min at 4 and 25°C. The results showed that simultaneous use of carvacrol or curcumin with LEDs at various temperatures exhibited significant antibacterial activity against the bacteria depending on the exposure time. The application of curcumin or carvacrol sourced via PDI in the originally developed system resulted in any significant changes in egg quality parameters and sensory properties. This study demonstrated that PDI-based system using curcumin or carvacrol as photosensitizers could be a potential tool for decontamination of eggs contaminated with S. Enteritidis PT4., (© 2025 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Bacterial infections have become a major global public health issue, particularly with the emergence of multidrug-resistant strains. Therefore, developing non-antibiotic antimicrobial agents is crucial for treating drug-resistant bacterial infections. Building on previous research into natural products as novel antibacterial agents, this study synthesized curcumin-derived carbon dots using curcumin and ethylenediamine as raw materials through a hydrothermal method. The resulting carbon dots not only improved the water solubility and stability of curcumin but also exhibited highly efficient broad-spectrum antibacterial activity. Detailed investigations into the antibacterial performance and mechanisms of the carbon dots were conducted through experiments such as minimum inhibitory concentration (MIC) determination, live/dead bacterial staining, morphological studies, nucleic acid concentration detection, and reactive oxygen species (ROS) detection. The results indicated that the carbon dots significantly damaged the structural integrity of bacteria and generated large amounts of ROS. They exhibited remarkable antibacterial effects against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and effectively inhibited drug-resistant MRSA. Their antibacterial efficacy was notably superior to that of broad-spectrum antibiotics such as chloramphenicol and Sulfadiazine. This study highlights the potential application of curcumin-derived carbon dots in combating bacterial infections and provides valuable insights for developing novel antibacterial agents derived from natural products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Inhalation drug delivery can deliver high doses of chemotherapeutic drugs to the lung tumor. This study evaluates the efficacy and the mechanistic pathways of nebulized Cur NPs at various sizes to treat multidrug resistant lung cancer., Methods and Results: Cur-NPs (30 nm and 200 nm) were nebulized separately onto the multidrug-resistant lung cancer cells (H69AR). Smaller NPs induced significantly higher cell death owing to a higher rate of particle internalization via dynamin-dependent clathrin-mediated endocytosis. Owing to the higher lysosome trafficking of Cur-NP30 nm compared to Cur-NP 200 nm , oxidation of lysosome was higher (0.47 ± 0.08 vs 0.38 ± 0.08), contributing to significantly higher mitochondrial membrane potential loss (1.57 ± 0.17 vs 1.30 ± 0.11). MRP1 level in H69AR cells was reduced from 352 ± 12.3 ng/µg of protein (untreated cells) to 287 ± 12 ng/µg of protein (Cur-NP 30 nm ) and 303 ± 13.4 ng/µg of protein (Cur-NP 200 nm ). NF-κB, and various cytokine expressions were reduced after treatment with nebulized Cur-NPs., Conclusions: Nebulized Cur-NPs formulations could be internalized into the H69AR cells. The Cur-NPs toxicity toward the H69AR was size and time-dependent. Cur-NP30 nm was more effective than Cur-NP200 nm to retain within the cells to exert higher oxidative stresss-induced cell death.

In this study, a simple but novel preparation method was developed by heating a mixture of dipotassium glycyrrhizinate (DG) and bisdemethoxycurcumin (BDMC) in aqueous solution, and a DG self-assembled nanomicelles-loading BDMC (named B@DNM) ophthalmic solution was successfully fabricated with this heating-driven process. AutoDock simulation analysis revealed that Pi-Alkyl hydrophobic interactions between BDMC and DG played important role in this self-assembled B@DNM. The optimized B@DNM, with a DG:BDMC mass ratio of 40:1 and heating time of 6 h, had a high encapsulation efficacy of 96.70 ± 0.13 % and particle sizes of 117.50 ± 6.07 nm. The apparent solubility of BDMC in B@DNM was significantly improved from bare BDMC (10.40 ± 0.16 μg/ml to 1405.60 ± 6.78 μg/ml) in artificial tears after 4 h incubation. B@DNM had great storage stability as an aqueous ophthalmic solution. B@DNM showed significantly improved in vitro antioxidant activity. Ex vivo hen's egg test-chorioallantoic membrane assay and long-term in vivo mouse eye tolerance evaluation showed that B@DNM had good ocular safety profiles. B@DNM showed improved in vivo corneal permeation profiles in the mouse eyes. Topical administration of B@DNM achieved a significantly improved efficacy on a mouse model of dry eye disease (DED), including accelerating corneal wound healing, restoring corneal sensitivity, and inhibiting corneal neovascularization. Regulation of the high mobility group box 1 signal pathway was involved in B@DNM's strong therapeutic effects. These findings demonstrate that heating is a simple method to prepare ocular nanoformulation with DG, and B@DNM might be a potential ocular drug for treating DED., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Brain aging is a multifactorial process that includes a reduction in the biological and metabolic activity of individuals. Oxidative stress and inflammatory processes are characteristic of brain aging. Given the current problems, the need arises to implement new therapeutic approaches. Polyoxidovanadates (POV), as well as curcumin, have stood out for their participation in a variety of biological activities. This work aimed to evaluate the coupling of metavanadate and curcumin (Cuma-MV) on learning, memory, redox balance, neuroinflammation, and cell death in the hippocampal region (CA1 and CA3) and dentate gyrus (DG) of aged rats. Rats 18 months old were administered a daily dose of curcumin (Cuma), sodium metavanadate (MV), or Cuma-MV for two months. The results demonstrated that administration of Cuma-MV for 60 days in aged rats improved short- and long-term recognition memory, decreased reactive oxygen species, and substantially improved lipoperoxidation in the hippocampus. Furthermore, the activity of superoxide dismutase and catalase increased in animals treated with Cuma-MV. It is important to highlight that the treatment with Cuma-MV exhibited a significantly greater effect than the treatments with MV or Cuma in all the parameters evaluated. Finally, we conclude that Cuma-MV represents a potential therapeutic option in the prevention and treatment of cognitive decline associated with aging., (© 2025 Wiley Periodicals LLC.)

Zein, a maize protein, has been explored for constructing potential biomaterial due to its hydrophobic nature, self-assembly capability, and biocompatibility. In its nanoparticulate form, zein is a promising material for drug delivery applications, particularly in cancer treatment. Despite the importance of colloidal stability for effective drug delivery, systematic studies investigating the effect of various surface modifying agents (MAs) on the zein nanoparticles (ZNPs)-based formulations are limited. This study employs quality-by-design (QbD) approach to optimize curcumin-loaded ZNPs, enhancing colloidal stability, size, and drug-encapsulation efficiency using different MAs for potential cancer therapy. Gum arabic (GA) emerged as the optimal stabilizer, with GA-stabilized curcumin-loaded ZNPs (GA-Cur-ZNPs) achieving a particle size of 184.8 ± 2.85 nm, zeta potential of -23.4 ± 0.56 mV and 87.1 ±1.55 % drug encapsulation efficiency, along with excellent colloidal stability over two months. The optimal formulation also demonstrated sustained release of Cur over 72 h. GA-Cur-ZNPs demonstrated lower IC 50 values and higher anti-proliferative effects on three different cancer cell lines compared to the free drug, while also exhibiting superior intracellular uptake. With negligible toxicity to human dermal fibroblast cells, the optimized Cur-GA-ZNPs show promise for safe and effective killing of cancer cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Breast cancer ranks among the most prevalent cancers. Enhancing the effectiveness of chemotherapy and patient survival is the objective of many studies. In the literature, no study has investigated the combined effect of vitamin c and curcumin with chemotherapy drugs on cell viability in the MCF-7 cell line, nor the mechanism of inflammation induced by cancer drugs, both in vitro and in silico. Thus, the purpose of this study was to assess the synergistic effect of curcumin and vitamin c in combination with the chemotherapy drugs 5-fluorouracil and doxorubicin. The cytokine hub genes of the Toll-like receptor pathway for the administered drugs were identified using the Cytoscape program, and docking studies were conducted via the Cb Dock2 website. In silico analyses indicated that doxorubicin and curcumin displayed comparable characteristics, achieving the highest interaction scores (-10) with marker proteins, whereas 5-fluorouracil and vitamin c showed lower interaction scores. Cell viability was evaluated through MTT analysis and AO/PI staining, while the expression of inflammation-related markers IL-6, IL-10, and TNF-α proteins determined using the ELISA method. After 24 h, the cell viability of the chemotherapeutic drugs administered in combination with curcumin decreased by up to 28%. Subsequently, applications at 48 and 72 h were performed. These results indicate that the effect of curcumin on cell viability is significant when combined with chemotherapy drugs. In the ELISA test, a 52% expression of IL-6 was noted in MCF-7 cells treated with curcumin, whereas the IL-6 level decreased to 15% in the other experimental groups. An increase was observed in the TNF-α expression with 5-fluorouracil and doxorubicin compared to the control, while a notable decrease was recorded in the applications with vitamin c and curcumin (p < 0.05). This study demonstrates that vitamin c and curcumin exhibit a synergistic effect with chemotherapeutic agents in the inflammatory system., (© 2024 Wiley Periodicals LLC.)

Multidrug resistance (MDR) due to the overexpression of the P-glycoprotein (P-gp) efflux pump remains a significant challenge in cancer therapy, also in breast cancer. Traditional pharmacological approaches have focused on using inhibitors to modulate P-gp expression and function. Curcumin, a polyphenol derived from Curcuma longa L., is one of the most extensively studied natural compounds with the potential as an effective P-gp inhibitor. Despite its promising attributes, the clinical application of P-gp inhibitors is complicated by P-gp's presence in healthy cells, such as those in the intestinal barrier and blood-brain barrier, which can lead to increased toxicity. To address these challenges, we developed a novel multifunctional nanomaterial by covalently bonding halloysite nanotubes (HNTs) with hectorite (Ht) and loading it with curcumin and doxorubicin. The efficacy of the co-delivery of curcumin and doxorubicin by HNTs-Ht nanomaterial was evaluated by cytotoxicity assays on MCF-7R cells, both in two-dimensional (2D) and in three-dimensional (3D) models. The obtained data show that curcumin causes increased doxorubicin accumulation by acting as a substrate for P-gp transport and as a stimulator of the adenosine triphosphate (ATP)-dependent drug efflux transporter on a doxorubicin-resistant breast cancer cell line. The results suggest that the HNTs-Ht nanomaterial could provide a promising approach to improve chemotherapy effectiveness by overcoming MDR and enhancing treatment outcomes., (© 2024 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) with clinical manifestations of respiratory distress and hypoxemia remains a significant cause of respiratory failure, boasting a persistently high incidence and mortality rate. Given the central role of M1 macrophages in the pathogenesis of acute lung injury (ALI), this study utilized the anti-inflammatory agent curcumin as a model drug. l-arginine (L-Arg) was employed as a targeting ligand, and chitosan was initially modified with l-arginine. Subsequently, it was utilized as a surface modifier to prepare inhalable nano-crystals loaded with curcumin (Arg-CS-Cur), aiming for specific targeting of pulmonary M1 macrophages. Compared with unmodified chitosan-curcumin nanocrystals (CS-Cur), Arg-CS-Cur exhibited higher uptake in vitro by M1 macrophages, as evidenced by flow cytometry showing the highest fluorescence intensity in the Arg-CS-Cur group (P < 0.01). In vivo accumulation was greater in inflamed lung tissues, as indicated by small animal imaging demonstrating higher lung fluorescence intensity in the DiR-Arg-CS-Cur group compared to the DiR-CS-Cur group in the rat ALI model (P < 0.05), peaking at 12 h. Moreover, Arg-CS-Cur demonstrated enhanced therapeutic effects in both LPS-induced RAW264.7 cells and ALI rat models. Specifically, treatment with Arg-CS-Cur significantly suppressed NO release and levels of TNF-α and IL-6 in RAW264.7 cells (p < 0.01), while in ALI rat models, expression levels of TNF-α and IL-6 in lung tissues were significantly lower than those in the model group (P < 0.01). Furthermore, lung tissue damage was significantly reduced, with histological scores significantly lower than those in the CS-Cur group (P < 0.01). In conclusion, these findings underscore the targeting potential of l-arginine-modified nanocrystals, which effectively enhance curcumin concentration in inflammatory environments by selectively targeting M1 macrophages. This study thus introduces novel perspectives and theoretical support for the development of targeted therapeutic interventions for acute inflammatory lung diseases, including ALI/ARDS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Methanolic extracts of Gleditsia triacanthos L. fruits and Gleditsia caspica Desf. leaves yielded two mono-carbonyl curcumin analogues; (1 E ,4 E )-1,5- bis (4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one [ 1 ], (1 E ,4 E )-1,5- bis (4-hydroxyphenyl)penta-1,4-dien-3-one [ 2 ], in addition to β -sitosterol [ 3 ], apigenin [ 4 ], quercetin-3`- O -methyl ether [ 5 ], rutin [ 6 ], quercetin [ 7 ], naringenin [ 8 ], eriodictyol [ 9 ], vitexin [ 10 ], isovitexin [ 11 ], gleditsin A [ 12 ]. The isolation of these compounds was reported here for the first time from the named plants. The separation and identification of curcumin analogues from genus Gleditsia in addition to 13 C NMR data of compound 2 were reported here for the first time. Compounds 1 and 2 were assayed in two hepatic cancer cells; HepG-2 and Huh-7. Compound 1 showed high cytotoxic activity against HepG-2 with an IC 50 value of 14.39 µM, compared with the standard, IC 50 = 12.44 μM.

Turmeric (Curcuma longa L.) has gained significant attention for its medicinal properties, yet its therapeutic applications are often limited by low aqueous solubility and susceptibility to environmental factors. This study investigates the formulation of a curcumin-rich turmeric extract-β-cyclodextrin inclusion complex (TUE-β-CD) to enhance its bioactivity and stability. Structural characterization and metabolite profiling of the inclusion complex were conducted using field-emission scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, Fourier transform infrared spectroscopy, and ultrahigh-performance liquid chromatography coupled with LTQ-Orbitrap-mass spectrometry (UHPLC-LTQ-Orbitrap-MS). Results revealed that the inclusion complexes exhibit distinct morphological, spectroscopic, crystalline, and thermal properties compared to both curcumin-rich TUE and β-CD, confirming successful encapsulation of turmeric metabolites within β-cyclodextrin cavities. Results of UHPLC-LTQ-Orbitrap-MS confirmed that β-CD had differential encapsulation efficiencies for bioactive compounds of turmeric. The results suggest that the inclusion complex significantly improves the thermal stability and bioactivity of turmeric extract, thereby enhancing its potential applications as a functional component in both food and non-food industries., (© 2024 Institute of Food Technologists.)

The development of biocompatible wound dressings containing therapeutic agents to accelerate wound healing is an interesting field of study in biomedical sciences. Polyvinyl alcohol (PVA) nanofibers were loaded with zinc oxide nanoparticles (ZnO NPs) and curcumin (Cur) through electrospinning. The dressings were characterized by SEM and XRD and FTIR. The antioxidant, antibacterial, and cytotoxic activities Cur/ZnO/PVA nano dressing were evaluated using DPPH radical scavenging assay, disc diffusion method, and MTT assay, respectively. Cur/ZnO/PVA nano dressing showed sustained Cur release about 19.7% and 61.1% after 8h and 168h, respectively. Cur/ZnO NPs/PVA mixture had higher antioxidant potential than PVA, ZnO NPs, and Cur. The dressing showed a good antibacterial effect. The in vivo wound healing effect of different types of prepared dressings, including PVA, Cur/PVA, Cur/ZnO/PVA, and ZnO/ PVA nanofibers, was also investigated. PVA dressing containing Cur/ZnO NPs resulted in the highest increase of wound contraction in rats. The assembly of Cur and ZnO NPs on PVA nanofibers could propose as an effective delivery method to improve the wound healing process. The investigated wound dressing could be commercialized and used on a large scale after proper further studies, including clinical trials., Competing Interests: Declarations. Ethical Approval: The animal experiment was performed according to the ethics guidelines of Shiraz University of Medical Sciences (ethical code: IR.SUMS.REC.1398.1231). Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to investigate the effects of curcumin-carbon dot conjugates (CUR-CD) on periodontitis. Porphyromonas gingivalis lipopolysaccharide (LPS) was used to establish periodontitis mode in vivo and in vitro. Histological analysis was conducted using hematoxylin and eosin (HE) staining. Bone morphogenetic protein 2 (BMP2) and secreted phosphoprotein 1 (OPN) expression was determined using immunohistochemistry. mRNA levels were detected using reverse transcription quantitative real-time PCR (RT-qPCR). Protein expression was determined using Western blot. N6-methyladenosine (m6A) enrichment was determined using methylated RNA immunoprecipitation (MeRIP) assay. Cytokine release was determined using enzyme-linked immunosorbent assay (ELISA) assay. Osteogenic differentiation was detected using alkaline phosphatase (ALP) staining. The results showed that CUR-CD inhibited the inflammatory response, as well as promoted bone healing in vivo and osteogenic differentiation in vitro. Moreover, CUR-CD downregulated methyltransferase 3 (METTL3), which inhibited m6A modification of endoplasmic reticulum to nucleus signaling 1 (IRElα) and downregulated IRElα expression. However, overexpression of IRElα reversed the effects of CUR-CD, stimulating inflammatory response and inhibiting bone healing and osteogenic differentiation. Collectively, CUR-CD inhibits the progression of periodontitis via downregulating IRElα. Therefore, CUR-CD may be an alternative strategy for periodontitis.