Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 3.801
1.
Chem Biol Drug Des ; 103(5): e14532, 2024 May.
Article En | MEDLINE | ID: mdl-38725089

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that causes severe liver damage, fibrosis, and scarring. Despite its potential to progress to cirrhosis or hepatic failure, approved drugs or treatments are currently unavailable. We developed 4,4-diallyl curcumin bis(2,2-hydroxymethyl)propanoate, also known as 35e, which induces upregulation of mitochondrial proteins including carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II, heat shock protein 60, and translocase of the outer mitochondrial membrane 20. Among these proteins, the upregulated expression of CPT-I was most prominent. CPT-I plays a crucial role in transporting carnitine across the mitochondrial inner membrane, thereby initiating mitochondrial ß-oxidation of fatty acids. Given recent research showing that CPT-I activation could be a viable pathway for NASH treatment, we hypothesized that 35e could serve as a potential agent for treating NASH. The efficacy of 35e in treating NASH was evaluated in methionine- and choline-deficient (MCD) diet- and Western diet (WD)-induced models that mimic human NASH. In the MCD diet-induced model, both short-term (2 weeks) and long-term (7 weeks) treatment with 35e effectively regulated elevated serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) concentrations and histological inflammation. However, the antisteatotic effect of 35e was obtained only in the short-term treatment group. As a comparative compound in the MCD diet-induced model, curcumin treatment did not produce significant regulatory effects on the liver triglyceride/total cholesterol, serum ALT/AST, or hepatic steatosis. In the WD-induced model, 35e ameliorated hepatic steatosis and hepatic inflammation, while increasing serum AST and hepatic lipid content. A decrease in epididymal adipose tissue weight and serum free fatty acid concentration suggested that 35e may promote lipid metabolism or impede lipid accumulation. Overall, 35e displayed significant antilipid accumulation and antifibrotic effects in the two complementary mice models. The development of new curcumin derivatives with the ability to induce CPT-I upregulation could further underscore their efficacy as anti-NASH agents.


Curcumin , Disease Models, Animal , Methionine , Non-alcoholic Fatty Liver Disease , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Methionine/metabolism , Methionine/deficiency , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/therapeutic use , Mice , Male , Diet, Western/adverse effects , Mice, Inbred C57BL , Carnitine O-Palmitoyltransferase/metabolism , Liver/metabolism , Liver/drug effects , Liver/pathology , Propionates/pharmacology , Propionates/therapeutic use , Propionates/metabolism , Humans , Choline/metabolism , Choline/pharmacology
2.
Sci Rep ; 14(1): 10499, 2024 05 07.
Article En | MEDLINE | ID: mdl-38714740

Improving the efficacy of chemotherapy remains a key challenge in cancer treatment, considering the low bioavailability, high cytotoxicity, and undesirable side effects of some clinical drugs. Targeted delivery and sustained release of therapeutic drugs to cancer cells can reduce the whole-body cytotoxicity of the agent and deliver a safe localized treatment to the patient. There is growing interest in herbal drugs, such as curcumin, which is highly noted as a promising anti-tumor drug, considering its wide range of bioactivities and therapeutic properties against various tumors. Conversely, the clinical efficacy of curcumin is limited because of poor oral bioavailability, low water solubility, instability in gastrointestinal fluids, and unsuitable pH stability. Drug-delivery colloid vehicles like liposomes and nanoparticles combined with microbubbles and ultrasound-mediated sustained release are currently being explored as effective delivery modes in such cases. This study aimed to synthesize and study the properties of curcumin liposomes (CLs) and optimize the high-frequency ultrasound release and uptake by a human breast cancer cell line (HCC 1954) through in vitro studies of culture viability and cytotoxicity. CLs were effectively prepared with particles sized at 81 ± 2 nm, demonstrating stability and controlled release of curcumin under ultrasound exposure. In vitro studies using HCC1954 cells, the combination of CLs, ultrasound, and Definity microbubbles significantly improved curcumin's anti-tumor effects, particularly under specific conditions: 15 s of continuous ultrasound at 0.12 W/cm2 power density with 0.6 × 107 microbubbles/mL. Furthermore, the study delved into curcumin liposomes' cytotoxic effects using an Annexin V/PI-based apoptosis assay. The treatment with CLs, particularly in conjunction with ultrasound and microbubbles, amplified cell apoptosis, mainly in the late apoptosis stage, which was attributed to heightened cellular uptake within cancer cells.


Curcumin , Drug Delivery Systems , Liposomes , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/administration & dosage , Humans , Liposomes/chemistry , Cell Line, Tumor , Drug Delivery Systems/methods , Cell Survival/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Microbubbles , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Ultrasonic Waves , Drug Liberation , Apoptosis/drug effects
3.
J Agric Food Chem ; 72(19): 11140-11152, 2024 May 15.
Article En | MEDLINE | ID: mdl-38703140

Recently, oral deliverable strategies of multiple nutraceuticals for ulcerative colitis (UC) mitigation have attracted increasing attention. This study aimed to fabricate facile oral assemblies loaded with egg-white-derived peptides (EWDP) and curcumin based on carboxymethyl chitosan (CMCS) and an γ-cyclodextrin metal-organic framework (MOF). Herein, outer CMCS could coassemble with EWDP (both nutraceuticals and building blocks) into cobweb-like fibrils to promote bridging with inner MOF via coordinative noncovalent interactions (hydrogen bonding, hydrophobic interaction, and electrostatic interaction). Compared with conventional γ-cyclodextrin/MOF-based composites, the above coassembly could also endow the biocompatible assemblies with superior nanoscale colloidal properties, processing applicability (curcumin storage stability, bioaccessibility, and aqueous solubility), and bioactivity. Moreover, the oral synergism of EWDP and curcumin (initially nonsynergistic) for UC mitigation was achieved by alleviating inflammatory damage and gut microbiota imbalance. Overall, the novel assemblies could be a promising amplifier and platform to facilitate oral formulations of various nutraceuticals for food processing and UC relief.


Colitis, Ulcerative , Curcumin , Metal-Organic Frameworks , Peptides , Curcumin/chemistry , Curcumin/administration & dosage , Metal-Organic Frameworks/chemistry , Animals , Humans , Peptides/chemistry , Peptides/administration & dosage , Colitis, Ulcerative/drug therapy , Mice , Chitosan/chemistry , Egg White/chemistry , Polysaccharides/chemistry , Male , Administration, Oral , Drug Synergism , gamma-Cyclodextrins/chemistry , Drug Carriers/chemistry , Egg Proteins/chemistry
4.
Carbohydr Polym ; 337: 122160, 2024 Aug 01.
Article En | MEDLINE | ID: mdl-38710575

Sterilisation technologies are essential to eliminate foodborne pathogens from food contact surfaces. However, most of the current sterilisation methods involve high energy and chemical consumption. In this study, a photodynamic inactivation coating featuring excellent antibacterial activity was prepared by dispersing curcumin as a plant-based photosensitiser in a chitosan solution. The coating generated abundant reactive oxygen species (ROS) after light irradiation at 420 nm, which eradicated ≥99.999 % of Escherichia coli O157:H7. It was also found that ROS damaged the cell membrane, leading to the leakage of cell contents and cell shrinkage on the basis of chitosan. In addition, the production of ROS first excited the bacterial antioxidant defence system resulting in the increase of peroxidase (POD) and superoxide dismutase (SOD). ROS levels exceed its capacity, causing damage to the defence system and further oxidative decomposition of large molecules, such as DNA and proteins, eventually leading to the death of E. coli O157:H7. We also found the curcumin/chitosan coating could effectively remove E. coli O157:H7 biofilms by oxidative of extracellular polysaccharides and proteins. All the contributors made the chitosan/curcumin coating an efficient detergent comparable with HClO.


Anti-Bacterial Agents , Biofilms , Chitosan , Curcumin , Escherichia coli O157 , Photosensitizing Agents , Reactive Oxygen Species , Chitosan/chemistry , Chitosan/pharmacology , Curcumin/pharmacology , Curcumin/chemistry , Escherichia coli O157/drug effects , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Reactive Oxygen Species/metabolism , Biofilms/drug effects , Food Microbiology , Light
5.
Sci Rep ; 14(1): 10117, 2024 05 02.
Article En | MEDLINE | ID: mdl-38698033

In this research, the hydrophilic structure of multi-walled carbon nanotubes (MWCNTs) was modified by synthesizing polycitric acid (PCA) and attaching folic acid (FA) to create MWCNT-PCA-FA. This modified nanocomplex was utilized as a carrier for the lipophilic compound curcumin (Cur). Characterization techniques including TGA, TEM, and UV-visible spectrophotometry were used to analyze the nanocomplex. The mechanism of cancer cell death induced by MWCNT-PCA-FA was studied extensively using the MTT assay, colony formation analysis, cell cycle assessment via flow cytometry, and apoptosis studies. Furthermore, we assessed the antitumor efficacy of these targeted nanocomplexes following exposure to laser radiation. The results showed that the nanocomposites and free Cur had significant toxicity on melanoma cancer cells (B16F10 cells) while having minimal impact on normal cells (NHDF cells). This selectivity for cancerous cells demonstrates the potential of these compounds as therapeutic agents. Furthermore, MWCNT-PCA-FA/Cur showed superior cytotoxicity compared to free Cur alone. Colony formation studies confirmed these results. The researchers found that MWCNT-FA-PCA/Cur effectively induced programmed cell death. In photothermal analysis, MWCNT-PCA-FA/Cur combined with laser treatment achieved the highest mortality rate. These promising results suggest that this multifunctional therapeutic nanoplatform holds the potential for combination cancer therapies that utilize various established therapeutic methods.


Curcumin , Nanotubes, Carbon , Curcumin/pharmacology , Curcumin/chemistry , Nanotubes, Carbon/chemistry , Cell Line, Tumor , Humans , Mice , Animals , Folic Acid/chemistry , Apoptosis/drug effects , Melanoma/drug therapy , Melanoma/pathology , Melanoma/therapy , Photothermal Therapy/methods , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Drug Carriers/chemistry , Cell Survival/drug effects
6.
Molecules ; 29(9)2024 Apr 26.
Article En | MEDLINE | ID: mdl-38731476

Although the wide variety of bioactivities of curcumin has been reported by researchers, the clinical application of curcumin is still limited due to its poor aqueous solubility. In view of this, a series of dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized (compounds 1-15). Acetate of these derivatives were prepared (compounds 1a-15a). The Mannich reaction and aldol condensation reaction are the main reactions involved in this study. Compounds 6, 10, 12, 3a, 5a, 6a, 7a, 8a, 10a, 11a, 12a, 13a, 14a, and 15a exhibited better in vitro anti-inflammatory activity compared to curcumin in the RAW264.7 cell line. Compounds 5, 1a, 5a, 8a, and 12a exhibited better in vitro antioxidant activity compared to curcumin in the PC 12 cell line. Compounds 11, 13, 5a, 7a, and 13a exhibited better in vitro radiation protection compared to curcumin in the PC 12 cell line. The aqueous solubilities of all the curcumin derivative acetates were greatly improved compared to curcumin.


Anti-Inflammatory Agents , Antioxidants , Curcumin , Radiation-Protective Agents , Solubility , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/chemical synthesis , Curcumin/analogs & derivatives , Animals , Mice , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/chemical synthesis , RAW 264.7 Cells , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/chemical synthesis , Radiation-Protective Agents/pharmacology , Radiation-Protective Agents/chemical synthesis , Radiation-Protective Agents/chemistry , Drug Design , Structure-Activity Relationship , Molecular Structure , PC12 Cells , Rats , Water/chemistry
7.
Eur J Pharm Sci ; 197: 106766, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38615970

One of the most frequent causes of respiratory infections are viruses. Viruses reaching the airways can be absorbed by the human body through the respiratory mucosa and mainly infect lung cells. Several viral infections are not yet curable, such as coronavirus-2 (SARS-CoV-2). Furthermore, the side effect of synthetic antiviral drugs and reduced efficacy against resistant variants have reinforced the search for alternative and effective treatment options, such as plant-derived antiviral molecules. Curcumin (CUR) and quercetin (QUE) are two natural compounds that have been widely studied for their health benefits, such as antiviral and anti-inflammatory activity. However, poor oral bioavailability limits the clinical applications of these natural compounds. In this work, nanoemulsions (NE) co-encapsulating CUR and QUE designed for nasal administration were developed as promising prophylactic and therapeutic treatments for viral respiratory infections. The NEs were prepared by high-pressure homogenization combined with the phase inversion temperature technique and evaluated for their physical and chemical characteristics. In vitro assays were performed to evaluate the nanoemulsion retention into the porcine nasal mucosa. In addition, the CUR and QUE-loaded NE antiviral activity was tested against a murine ß-COV, namely MHV-3. The results evidenced that CUR and QUE loaded NE had a particle size of 400 nm and retention in the porcine nasal mucosa. The antiviral activity of the NEs showed a percentage of inhibition of around 99 %, indicating that the developed NEs has interesting properties as a therapeutic and prophylactic treatment against viral respiratory infections.


Administration, Intranasal , Antiviral Agents , Curcumin , Emulsions , Quercetin , Curcumin/administration & dosage , Curcumin/pharmacology , Curcumin/chemistry , Quercetin/administration & dosage , Quercetin/pharmacology , Quercetin/chemistry , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Mice , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Swine , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/virology , Respiratory Tract Infections/prevention & control , Nasal Mucosa/metabolism , Nasal Mucosa/drug effects , Nasal Mucosa/virology , SARS-CoV-2/drug effects , COVID-19 Drug Treatment , Humans
8.
Int J Biol Macromol ; 267(Pt 1): 131372, 2024 May.
Article En | MEDLINE | ID: mdl-38580024

Clinically, open wounds caused by accidental trauma and surgical lesion resection are easily infected by external bacteria, hindering wound healing. Antibacterial photodynamic therapy has become a promising treatment strategy for wound infection. In this study, a novel antibacterial nanocomposite material (QMC NPs) was synthesized by curcumin, quaternized chitosan and mesoporous polydopamine nanoparticles. The results showed that 150 µg/mL QMC NPs had good biocompatibility and exerted excellent antibacterial activity against Staphylococcus aureus and Escherichia coli after blue laser irradiation (450 nm, 1 W/cm2). In vivo, QMC NPs effectively treated bacterial infection and accelerated the healing of infected wounds in mice.


Anti-Bacterial Agents , Chitosan , Curcumin , Escherichia coli , Indoles , Nanoparticles , Polymers , Staphylococcus aureus , Chitosan/chemistry , Chitosan/pharmacology , Indoles/chemistry , Indoles/pharmacology , Curcumin/pharmacology , Curcumin/chemistry , Polymers/chemistry , Polymers/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Nanoparticles/chemistry , Animals , Mice , Staphylococcus aureus/drug effects , Porosity , Escherichia coli/drug effects , Microbial Sensitivity Tests , Wound Healing/drug effects , Bacterial Infections/drug therapy
9.
Int J Biol Macromol ; 267(Pt 1): 131388, 2024 May.
Article En | MEDLINE | ID: mdl-38608982

We developed a facile method for the fabrication of a biodegradable delivery system composed of two blocks: curdlan and curcumin. This was achieved by chemical functionalization of curdlan through tosylation, amination followed by complexation with curcumin. A comprehensive evaluation of structural characterization and component stability showed that cur-cum complex exhibited better anticancer properties with enhanced thermal properties. The cur-cum complex shows pH sensitive sustained release behaviour with higher release at acidic pH and kinetic data of drug release follows the Korsmeyer-Peppas model. The cur-cum complex has ability to block the proliferation of the MCF-7 cell line as revealed by MTT assay which showed increased toxicity of cur-cum complex against these cell lines. The results obtained from western blot analysis demonstrated that the co-administration of cur and cum effectively induced apoptosis in MCF-7 cells. This effect was observed by a considerable upregulation of the Bcl-2/Bax ratio, a decline in mRNA expression of LDHA, level of lactate and LDH activity. The results clearly depict the role of functionalized curdlan as efficient carrier for curcumin delivery with prolonged, sustained release and enhanced bioavailability, thereby improving the overall anticancer activity.


Apoptosis , Breast Neoplasms , Curcumin , Drug Liberation , beta-Glucans , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/administration & dosage , beta-Glucans/chemistry , beta-Glucans/pharmacology , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , MCF-7 Cells , Female , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Drug Carriers/chemistry , Drug Delivery Systems , Cell Proliferation/drug effects , Hydrogen-Ion Concentration
10.
Int J Mol Sci ; 25(8)2024 Apr 16.
Article En | MEDLINE | ID: mdl-38673967

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.


Antineoplastic Agents , Curcumin , Curcumin/analogs & derivatives , Magnesium , beta-Cyclodextrins , beta-Cyclodextrins/chemistry , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/pharmacokinetics , Humans , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Magnesium/chemistry , Apoptosis/drug effects , Female , Cell Line, Tumor , STAT3 Transcription Factor/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Cell Movement/drug effects , Solubility , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Chick Embryo , Matrix Metalloproteinase 9/metabolism
11.
Nanoscale ; 16(18): 8843-8850, 2024 May 09.
Article En | MEDLINE | ID: mdl-38644775

Extensive modifications have been made to the synthesis protocol for porous silica particles to improve the shape, size and yield percentage, but problems associated with improvement in biodegradability and decrease in chances to induce side effects still remain a concern. To circumvent these limitations, a facile modification strategy has been employed through in situ carbonization of porous silica particles. Herein, carbon particles were integrated within porous silica core-shell particles (Si-P-CNPs) during the synthesis process and found to preserve the ordered structural morphology. Curcumin was used as a model drug for loading in prepared Si-P-CNPs whereas lung cancer cells were used as a model system to study the in vitro fate. These Si-P-CNPs showed improved drug loading, drug effectivity, biodegradability and avoidance of interaction with transforming growth factor ß1 (TGF-ß1) indicating the possibility of reducing the chances of lung fibrosis and thereby enhancing the safety profile over conventional porous silica particles.


Carbon , Curcumin , Drug Carriers , Silicon Dioxide , Transforming Growth Factor beta1 , Silicon Dioxide/chemistry , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/chemistry , Humans , Porosity , Drug Carriers/chemistry , Carbon/chemistry , Curcumin/chemistry , Curcumin/pharmacology , A549 Cells , Cell Line, Tumor , Fibrosis , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology
12.
J Mater Chem B ; 12(19): 4642-4654, 2024 May 15.
Article En | MEDLINE | ID: mdl-38592460

The therapeutic efficacy of Fenton or Fenton-like nanocatalysts is usually restricted by the inappropriate pH value and limited concentration of hydrogen peroxide (H2O2) at the tumor site. Herein, calcium carbonate (CaCO3)-mineralized cobalt silicate hydroxide hollow nanocatalysts (CSO@CaCO3, CC) were synthesized and loaded with curcumin (CCC). This hybrid system can simultaneously realize nanocatalytic therapy, chemotherapy and calcium overload. With the stabilization of liposomes, CCC is able to reach the tumor site smoothly. The CaCO3 shell first degrades in an acidic tumor environment, releasing Cur and Ca2+, and the pH value of the tumor is increased simultaneously. Then the exposed CSO catalyzes the Fenton-like reaction to convert H2O2 into ˙OH and enhances the cytotoxicity of curcumin (Cur) by catalytically oxidizing it to a ˙Cur radical. Curcumin not only induces the chemotherapy effect but also serves as a nucleophilic ligand and an electron donor in the catalytic system, enhancing the Fenton-like activity of CCC by electron transfer. In addition, calcium overload also amplifies the efficacy of ROS-based therapy. In vitro and in vivo results show that CCC exhibited an excellent synergistic tumor inhibition effect without any clear side effect. This work proposes a novel concept of nanocatalytic therapy/chemotherapy synergistic mechanism by the ligand-induced enhancement of Fenton-like catalytic activity, and inspires the construction of combined therapeutic nanoplatforms and multifunctional nanocarriers for drug and ion delivery in the future.


Antineoplastic Agents , Calcium , Cobalt , Curcumin , Nanoparticles , Curcumin/chemistry , Curcumin/pharmacology , Cobalt/chemistry , Cobalt/pharmacology , Humans , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Mice , Calcium/chemistry , Calcium/metabolism , Nanoparticles/chemistry , Catalysis , Calcium Carbonate/chemistry , Ligands , Particle Size , Mice, Inbred BALB C , Drug Carriers/chemistry , Drug Screening Assays, Antitumor , Cell Proliferation/drug effects , Female , Cell Survival/drug effects , Cell Line, Tumor
13.
Mikrobiyol Bul ; 58(2): 182-195, 2024 Apr.
Article Tr | MEDLINE | ID: mdl-38676585

In recent years, isolation of resistant Leishmania species to drugs in use has made it necessary to search alternative molecules that may be drug candidates. In this study, it was aimed to investigate the cytotoxic and in vitro antileishmanial activity of hybrid silver nanoparticle (AgNP) complexes. In this study, three types of nanoparticles (NPs), oxidized amylose-silver (OA-Ag) NPs, oxidized amylose-curcumin (OA-Cur) NPs and oxidized amylose-curcumin-silver (OA-CurAgNP) nanoparticles were synthesized. The cytotoxic activity of the synthesized nanoparticles was determined against L929 mouse fibroblasts and the in vitro antileishmanial activity was determined against Leishmania tropica, Leishmania infantum and Leishmania donovani isolates by the broth microdilution method. It was observed that the hybrid OA-CurAgNP complex obtained by combining curcumin and silver nanoparticles showed cytotoxic effects against L929 mouse fibroblasts at concentrations of 1074 µg/mL and above. IC50 values expressing the antileishmanial activity of the hybrid OA-CurAgNP complex against L.tropica, L.infantum and L.donovani isolates, were found to vary between 95-121 µg/mL, 202-330 µg/mL and 210-254 µg/mL, respectively. Resistance development has emerged as a major challenge in the treatment of leishmaniasis in recent times. Metallic nanoparticles are considered excellent candidates for medical applications due to their chemical and physical properties, as well as their prolonged circulation in the body. The current drugs used for leishmaniasis treatment are highly toxic, while nanoparticles offer advantages such as low toxicity and easy cellular uptake due to their nanoscale dimensions. The identification of strong efficacy in these particles may contribute scientific evidence for their potential use in leishmaniasis treatment. Therefore, the therapeutical value of OA-CurAgNP complex alone in combination with existing drugs should be examined.


Antiprotozoal Agents , Curcumin , Fibroblasts , Leishmania infantum , Leishmania tropica , Metal Nanoparticles , Silver , Animals , Mice , Silver/pharmacology , Silver/chemistry , Metal Nanoparticles/chemistry , Curcumin/pharmacology , Curcumin/chemistry , Leishmania tropica/drug effects , Leishmania infantum/drug effects , Fibroblasts/drug effects , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/toxicity , Leishmania donovani/drug effects , Inhibitory Concentration 50 , Cell Line
14.
Inorg Chem ; 63(17): 7955-7965, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38634659

Curcuminoids and their complexes continue to attract attention in medicinal chemistry, but little attention has been given to their metabolic derivatives. Here, the first examples of (arene)Ru(II) complexes with curcuminoid metabolites, tetrahydrocurcumin (THcurcH), and tetrahydrobisdesmethoxycurcumin (THbdcurcH) were prepared and characterized. The neutral complexes [Ru(arene)(THcurc)Cl] and [Ru(arene)(THbdcurc)Cl] (arene = cymene, benzene, or hexamethylbenzene) were characterized by NMR spectroscopy and ESI mass spectrometry, and the crystal structures of the three complexes were determined by X-ray diffraction analysis. Compared to curcuminoids, these metabolites lose their conjugated double bond system responsible for their planarity, showing unique closed conformation structures. Both closed and open conformations have been analyzed and rationalized by using density functional theory (DFT). The cytotoxicity of the complexes was evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR), human breast adenocarcinoma cells (MCF-7 and MCF-7CR), as well as against non-tumorigenic human embryonic kidney cells (HEK293) and human breast (MCF-10A) cells and compared to the free ligands, cisplatin, and RAPTA-C. There is a correlation between cellular uptake and the cytotoxicity of the compounds, suggesting that cellular uptake and binding to nuclear DNA may be the major pathway for cytotoxicity. However, the levels of complex binding to DNA do not strictly correlate with the cytotoxic potency, indicating that other mechanisms are also involved. In addition, treatment of MCF-7 cells with [Ru(cym)(THcurc)Cl] showed a significant decrease in p62 protein levels, which is generally assumed as a noncisplatin-like mechanism of action involving autophagy. Hence, a cisplatin- and a noncisplatin-like concerted mechanism of action, involving both apoptosis and autophagy, is possible.


Antineoplastic Agents , Coordination Complexes , Curcumin , Drug Screening Assays, Antitumor , Ruthenium , Humans , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/analogs & derivatives , Curcumin/metabolism , Ruthenium/chemistry , Ruthenium/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemical synthesis , Diarylheptanoids/chemistry , Diarylheptanoids/pharmacology , Diarylheptanoids/chemical synthesis , Cell Proliferation/drug effects , Molecular Structure , Cell Line, Tumor , Models, Molecular , Density Functional Theory , Cell Survival/drug effects , HEK293 Cells
15.
Molecules ; 29(8)2024 Apr 12.
Article En | MEDLINE | ID: mdl-38675577

Curcumin is a natural compound with a great pharmaceutical potential that involves anticancer, anti-inflammatory, antioxidant, and neuroprotective activity. Unfortunately, its low bioavailability, instability, and poor water solubility significantly deteriorate its clinical use. Many attempts have been made to overcome this issue, and encapsulating curcumin in a hydrogel matrix may improve those properties. Hydrogel formulation is used in many drug delivery forms, including classic types and novel forms such as self-assembly systems or responsive to external factors. Reviewed studies confirmed better properties of hydrogel-stabilized curcumin in comparison to pure compound. The main enhanced characteristics were chemical stability, bioavailability, and water solubility, which enabled these systems to be tested for various diseases. These formulations were evaluated for wound healing properties, effectiveness in treating skin diseases, and anticancer and regenerative activity. Hydrogel formulation significantly improved biopharmaceutical properties, opening the opportunity to finally see curcumin as a clinically approved substance and unravel its therapeutic potential.


Curcumin , Hydrogels , Curcumin/chemistry , Curcumin/pharmacology , Hydrogels/chemistry , Humans , Solubility , Biological Availability , Drug Delivery Systems , Animals , Wound Healing/drug effects , Drug Carriers/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
16.
Biochemistry (Mosc) ; 89(3): 417-430, 2024 Mar.
Article En | MEDLINE | ID: mdl-38648762

Platelets are known for their indispensable role in hemostasis and thrombosis. However, alteration in platelet function due to oxidative stress is known to mediate various health complications, including cardiovascular diseases and other health complications. To date, several synthetic molecules have displayed antiplatelet activity; however, their uses are associated with bleeding and other adverse effects. The commercially available curcumin is generally a mixture of three curcuminoids: curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Although crude curcumin is known to inhibit platelet aggregation, the effect of purified curcumin on platelet apoptosis, activation, and aggregation remains unclear. Therefore, in this study, curcumin was purified from a crude curcumin mixture and the effects of this preparation on the oxidative stress-induced platelet apoptosis and activation was evaluated. 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH) compound was used as an inducer of oxidative stress. Purified curcumin restored AAPH-induced platelet apoptotic markers like reactive oxygen species, intracellular calcium level, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release from mitochondria to the cytosol, and phosphatidyl serine externalization. Further, it inhibited the agonist-induced platelet activation and aggregation, demonstrating its antiplatelet activity. Western blot analysis confirms protective effect of the purified curcumin against oxidative stress-induced platelet apoptosis and activation via downregulation of MAPKs protein activation, including ASK1, JNK, and p-38. Together, these results suggest that the purified curcumin could be a potential therapeutic bioactive molecule to treat the oxidative stress-induced platelet activation, apoptosis, and associated complications.


Apoptosis , Blood Platelets , Curcumin , MAP Kinase Kinase Kinase 5 , Oxidative Stress , Curcumin/pharmacology , Curcumin/analogs & derivatives , Curcumin/chemistry , Apoptosis/drug effects , Oxidative Stress/drug effects , MAP Kinase Kinase Kinase 5/metabolism , Humans , Blood Platelets/drug effects , Blood Platelets/metabolism , MAP Kinase Signaling System/drug effects , Reactive Oxygen Species/metabolism , Platelet Activation/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism , Membrane Potential, Mitochondrial/drug effects , Platelet Aggregation/drug effects
17.
Int J Biol Macromol ; 267(Pt 2): 131563, 2024 May.
Article En | MEDLINE | ID: mdl-38626837

Excessive exudation from the wound site and the difficulty of determining the state of wound healing can make medical management more difficult and, in extreme cases, lead to wound deterioration. In this study, we fabricated a pH-sensitive colorimetric chronic wound dressing with self-pumping function using electrostatic spinning technology. It consisted of three layers: a polylactic acid-curcumin (PCPLLA) hydrophobic layer, a hydrolyzed polyacrylonitrile (HPAN) transfer layer, and a polyacrylonitrile-purple kale anthocyanin (PAN-PCA) hydrophilic layer. The results showed that the preparation of porous PLLA fiber membrane loaded with 0.2 % Cur was achieved by adjusting the spinning-related parameters, which could ensure that the composite dressing had sufficient anti-inflammatory, antibacterial and antioxidant properties. The HPAN membrane treated with alkali for 30 min had significantly enhanced liquid wetting ability, and the unidirectional transport of liquid could be achieved by simple combination with the 20 um PCPLLA fiber membrane. In addition, the 4 % loaded PCA showed more obvious color difference than the colorimetric membrane. In vivo and ex vivo experiments have demonstrated the potential of multifunctional dressings for the treatment of chronic wounds.


Bandages , Curcumin , Polyesters , Wound Healing , Hydrogen-Ion Concentration , Polyesters/chemistry , Porosity , Animals , Wound Healing/drug effects , Curcumin/chemistry , Curcumin/pharmacology , Acrylic Resins/chemistry , Anthocyanins/chemistry , Anthocyanins/pharmacology , Hydrophobic and Hydrophilic Interactions , Rats , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Male , Antioxidants/pharmacology , Antioxidants/chemistry , Brassica/chemistry
18.
Int J Biol Macromol ; 266(Pt 2): 131330, 2024 May.
Article En | MEDLINE | ID: mdl-38570003

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2-) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (-4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.


Metal-Organic Frameworks , Methicillin-Resistant Staphylococcus aureus , Nanoparticles , Photochemotherapy , Photosensitizing Agents , Polylysine , Reactive Oxygen Species , Polylysine/chemistry , Polylysine/pharmacology , Photochemotherapy/methods , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Nanoparticles/chemistry , Animals , Mice , Reactive Oxygen Species/metabolism , Hydrogen-Ion Concentration , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Drug Liberation , Curcumin/pharmacology , Curcumin/chemistry , Staphylococcal Infections/drug therapy
19.
Int J Biol Macromol ; 266(Pt 2): 131206, 2024 May.
Article En | MEDLINE | ID: mdl-38574919

In this study, cinnamic acid modified acid-ethanol hydrolyzed starch (CAES) with different degrees of substitution (DS) was fabricated to stabilize Pickering emulsions and probed their application for encapsulating curcumin (Cur). Successful preparation of CAES (with DS from 0.016 to 0.191) was confirmed by 1H NMR and FT-IR, and their physicochemical properties were characterized by XRD, SEM, and TGA. The biosafety evaluations and surface wettability confirmed the excellent safety and amphiphilic character of CAES. CAES-stabilized Pickering emulsion (CS-PE) exhibited different emulsion stability at different DS, with CS-PE (0.031) showing the highest stability. CLSM revealed that the CAES (0.031) formed a dense barrier on the surface of the oil droplets, preventing them from coalescing. The CS-PE (0.031) achieved effective encapsulation of Cur (up to 96.2 %). Compared with free Cur, CS-PE (0.031) exhibited better photochemical stability, higher free fatty acids (FFA) release, and enhanced bioaccessibility. These studies suggested that CAES may serve as a promising emulsifier for stabilizing Pickering emulsions to encapsulate and deliver hydrophobic bioactive compounds.


Curcumin , Emulsifying Agents , Emulsions , Starch , Curcumin/chemistry , Starch/chemistry , Emulsions/chemistry , Emulsifying Agents/chemistry , Hydrophobic and Hydrophilic Interactions , Cinnamates/chemistry , Drug Compounding
20.
Food Chem ; 449: 139233, 2024 Aug 15.
Article En | MEDLINE | ID: mdl-38593725

This investigation was focused on the impact of cold plasma (CP) on the extraction of curcumin and bioactive compounds of turmeric powder (TP). TP was treated with CP at different applied voltages (10, 20, and 30 kV), with various exposure times (10, 20, and 30 min). The curcumin content was highest at 30 kV for 10 min with a yield of 46.49 mg/g of TP. Total phenols significantly (p < 0.05) enhanced from 163.91 to 360.78 mg GAE/g DW accompanied by a remarkable 16% increment in total flavonoids, paralleled by a 26% increment in antioxidants as of control. Nuclear magnetic resonance spectra justified the extraction of curcuminoids. Moreover, micrographs displayed cell lysis in the treated powder. CP has exhibited a positive effect on surface colour parameters and thermal properties of TP. Overall, CP technology can be tailored for better curcumin extraction and the enhancement of phytochemicals.


Antioxidants , Curcuma , Curcumin , Phytochemicals , Plant Extracts , Plasma Gases , Powders , Curcuma/chemistry , Curcumin/chemistry , Curcumin/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Plasma Gases/chemistry , Plasma Gases/pharmacology , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Powders/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification
...