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1.
Oxid Med Cell Longev ; 2022: 8923615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35941902

RESUMO

Retinal degeneration is the major and principal cause behind many incurable blindness diseases. Several studies indicated the neuroprotective effect of Curcuma longa in eye pathologies, specifically retinopathy. However, the molecular mechanism behind its effect has not been completely elucidated. Using an ex vivo model of retinal degeneration obtained from an ex vivo optic nerve cut (ONC), we demonstrated that Curcuma extract (Cur) exerted a neuroprotective effect. Importantly, Cur was able to modulate apoptosis and MAPK signaling pathway activation and prevent retinal ganglion cell (RGC) loss. Other well-known neuroprotective pharmacological tools, including memantine (Mem), citicoline (Cit), and ginkgolic acid (GA), were used to compare the potential mechanisms of Cur. The antioxidant activity of retinas treated with Cur following optic nerve cut was significantly higher than control, but Cur failed to change the retina glutamate content. Considering the antioxidant effect of Cur and taking advantage of our recent findings on the crosstalk between oxidative stress and post-translational protein modifiers, in particular, small ubiquitin-related modifier (SUMO), we were interested in exploring the effect of Cur on SUMOylation. We found that Cur significantly prevented the increase of protein SUMOylation, confirming our previous in vitro data indicating the cytoprotective effect of curcumin through modulating the oxidative stress and SUMO-JNK axis. Altogether, these results suggest that Curcuma protects the retina from degeneration via antioxidant activity and targets SUMOylation. Therefore, it might be considered for the combination therapy with other neuroprotective agents with different mechanisms in preclinical studies on retinal degeneration.


Assuntos
Curcumina , Fármacos Neuroprotetores , Degeneração Retiniana , Antioxidantes/farmacologia , Curcuma , Curcumina/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Degeneração Retiniana/tratamento farmacológico , Sumoilação
2.
Biomater Adv ; 138: 212870, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35913251

RESUMO

Drug delivery systems that not only show efficacy through multiple therapeutic pathways but also facilitate patient drug use and exhibit a high bioavailability profile represent a promising strategy in the treatment of Alzheimer's disease (AD). Here, donepezil (DO)/memantine (MM)/curcumin (CUR)-loaded electrospun nanofibers (NFs) were produced for the treatment of AD. DSC, XRD, and FT-IR studies demonstrated the complete incorporation of the drug into PVA/PVP NFs. The disintegration profile was improved by loading the drugs in PVA/PVP with fast wetting (less than 1 s), the start of disintegration (21 s), and dispersion in 110 s. The desired properties for sublingual application were achieved with the dissolution of NFs in 240 s. The cell viability in DO/MM/CUR-loaded NFs was similar to the control group after 48 h in the cell culture. DO/MM/CUR-loaded NFs enhanced the expressions of BDNF (13.5-fold), TUBB3 (8.9-fold), Neurog2 (5.6-fold), NeuroD1 (5.8-fold), Nestin (166-fold), and GFAP (115-fold). DO/MM/CUR-loaded NFs and powder of these drugs contained in these fibers were daily administered sublingually to intracerebroventricular-streptozotocin (icv-STZ) treated rats. DO/MM/CUR-loaded NFs treatment improved the short-term memory damage and enhanced memory, learning ability, and spatial exploration talent. Results indicated that the levels of Aß, Tau protein, APP, GSK-3ß, AChE, and TNF-α were significantly decreased, and BDNF was increased by DO/MM/CUR-loaded NFs treatment compared to the AD group. In the histopathological analysis of the hippocampus and cortex, neuritic plaques and neurofibrillary nodes were not observed in the rats treated with DO/MM/CUR-loaded NFs. Taken together, the sublingual route delivery of DO/MM/CUR-loaded NFs supports potential clinical applications for AD.


Assuntos
Doença de Alzheimer , Curcumina , Nanofibras , Doença de Alzheimer/tratamento farmacológico , Animais , Fator Neurotrófico Derivado do Encéfalo/uso terapêutico , Curcumina/farmacologia , Donepezila/uso terapêutico , Glicogênio Sintase Quinase 3 beta , Memantina/uso terapêutico , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier
3.
Cardiovasc Ther ; 2022: 3159717, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909950

RESUMO

Diabetes causes lipid peroxide to accumulate within cardiomyocytes. Furthermore, lipid peroxide buildup is a risk factor for ferroptosis. This study is aimed at examining whether curcumin can ameliorate ferroptosis in the treatment of diabetic cardiomyopathy. Hematoxylin and eosin and Masson sections were used to examine the morphology, arrangement, and degree of fibrosis of the myocardium of diabetic rabbit models. The expression levels of nuclear Nrf2, Gpx4, Cox1, and Acsl4 in diabetic animal and cell models were quantitatively analyzed using immunofluorescence and western blotting. Nrf2-overexpression lentivirus vectors were transfected into cardiomyocytes, and the protective effects of curcumin and Nrf2 on cardiomyocytes under high glucose stimulation were assessed using terminal deoxynucleotidyl transferase dUTP nick-end labelling and reactive oxygen species probes. Diabetes was found to disorder myocardial cell arrangement and significantly increase the degree of myocardial fibrosis and collagen expression in myocardial cells. Curcumin treatment can increase nuclear transfer of Nrf2 and the expression of Gpx4 and HO-1, reduce glucose induced myocardial cell damage, and reverse myocardial cell damage caused by the ferroptosis inducer erastin. This study confirmed that curcumin can promote the nuclear translocation of Nrf2, increase the expression of oxidative scavenging factors, such as HO-1, reduce excessive Gpx4 loss, and inhibit glucose-induced ferroptosis in cardiomyocytes. This highlights a potentially new therapeutic route for investigation for the treatment diabetic cardiomyopathy.


Assuntos
Curcumina , Diabetes Mellitus , Cardiomiopatias Diabéticas , Ferroptose , Animais , Apoptose , Curcumina/farmacologia , Cardiomiopatias Diabéticas/prevenção & controle , Glucose/toxicidade , Peróxidos Lipídicos/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Coelhos
4.
Drug Des Devel Ther ; 16: 2365-2382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910781

RESUMO

Background: As the main component of turmeric (Curcuma longa L.), curcumin is widely used in the treatment of various diseases. Previous studies have demonstrated that curcumin has great potential as a therapeutic agent, but the lack of understanding of the functional mechanism of the drug has hindered the widespread use of the natural product. In the present study, we used comprehensive bioinformatics analysis and in vitro experiments to explore the anti-tumor mechanism of curcumin. Materials and Methods: LUAD mRNA expression data were obtained from TCGA database and differentially expressed genes (DEGs) were identified using R software. Functional enrichment analysis was conducted to further clarify its biological properties and hub genes were identified by a protein-protein interaction (PPI) network analysis. Survival analysis and molecular docking were used to analyze the effectiveness of the hub genes. By an in vitro study, we evaluated whether curcumin could influence the proliferation, migration, and invasion activities of LUAD cells. Results: In this study, 1783 DEGs from LUAD tissue samples compared to normal samples were evaluated. Functional enrichment analysis and the PPI network revealed the characteristics of the DEGs. We performed a topological analysis and identified 10 hub genes. Of these, six genes (INS, GCG, SST, F2, AHSG, and NPY) were identified as potentially effective biomarkers of LUAD. The molecular docking results indicated that curcumin targets in regulating lung cancer may be INS and GCG. We found that curcumin significantly inhibited the proliferation, migration, and invasion of LUAD cells and significantly decreased the expression of the INS and GCG genes. Conclusion: The results of this study suggest that the therapeutic effects of curcumin on LUAD may be achieved through the intervention of INS and GCG, which may act as potential biomarkers for LUAD prevention and treatment.


Assuntos
Adenocarcinoma de Pulmão , Curcumina , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais , Biologia Computacional , Curcumina/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Simulação de Acoplamento Molecular
5.
Drug Deliv ; 29(1): 2481-2490, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35912830

RESUMO

The development of effective carriers enabling combination cancer therapy is of practical importance due to its potential to enhance the effectiveness of cancer treatment. However, most of the reported carriers are monofunctional in nature. The carriers that can be applied to concomitantly mediate multiple treatment modalities are highly deficient. This study fills this gap by reporting the design and fabrication of ROS-generating carbohydrate-based pH-responsive beads with intrinsic anticancer therapy and multidrug co-delivery capacity for combination cancer therapy. Sodium alginate (SA) microspheres and reduced graphene oxide (rGO)-embedded chitosan (CS) beads are developed via emulsion-templated ionic gelation for a combination therapy involving co-delivery of curcumin (CUR) and 5-fluororacil (5-FU). Drug-encapsulated microbeads are characterized by FTIR, DSC, TGA, XRD, and SEM. 5-FU and CUR-encapsulated microbeads are subjected to in vitro drug release studies at pH 6.8 and 1.2 at 37 °C. Various release kinetic parameters are evaluated. The results show that the Korsmeyer-Peppas model and non-Fickian release kinetics are best suited. The microspheres and microbeads are found to effectively act against MCF7 cells and show intrinsic anticancer capacity. These results indicate the promising performance of our beads in mediating combination drug therapy to improve the effectiveness of cancer treatment.


Assuntos
Quitosana , Curcumina , Neoplasias , Alginatos/química , Quitosana/química , Curcumina/química , Curcumina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Fluoruracila/química , Grafite , Humanos , Concentração de Íons de Hidrogênio , Microesferas , Espécies Reativas de Oxigênio
6.
Int J Med Sci ; 19(7): 1138-1146, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35919818

RESUMO

Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, can induce oxidative stress and cause renal disease progression. However, the different cytotoxic effects on renal cells between IS and PCS are not stated. Due to uremic toxins are generally found in CKD patients, the mechanisms of uremic toxins-induced renal injury are required to study. Curcumin has anti-oxidant, anti-inflammatory and anti-apoptotic effects which may be potential used to protect against renal damage. In contrast, curcumin also exert cytotoxic effects on various cells. In addition, curcumin may reduce or enhance cytotoxicity combined with different chemicals treatments. However, whether curcumin may influence uremic toxins-induced renal injury is unclear. The goal of this study is to compare the different cytotoxic effects on renal cells between IS and PCS treatment, as well as the synergistic or antagonistic effects by combination treatments with curcumin and PCS. Our experimental result shows the PCS exerts a stronger antiproliferative effect on renal tubular cells than IS treatment. In addition, our study firstly demonstrates that curcumin enhances PCS-induced cell cytotoxicity through caspase-dependent apoptotic pathway and cell cycle alteration.


Assuntos
Curcumina , Insuficiência Renal Crônica , Cresóis/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Humanos , Indicã/metabolismo , Indicã/toxicidade , Rim/metabolismo , Insuficiência Renal Crônica/metabolismo , Sulfatos , Ésteres do Ácido Sulfúrico/metabolismo , Ésteres do Ácido Sulfúrico/toxicidade
7.
Biomater Adv ; 137: 212806, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35929233

RESUMO

Decellularized extracellular matrix (ECM) has been widely used for wound healing. But, ECM failed to integrate tissue and restore the tissue function properly, when elevated levels of free radicals and biofilm formation occur at the wound site. Here, nanoemulgel systems were fabricated, considering the combinatorial approach of nanotechnology (nanoceria and curcumin nanoemulsion) and ECM gel of goat small intestine submucosa. The curcumin was encapsulated in the nanoemulgel system to enhance bioavailability in terms of antibacterial, antioxidant, sustained release and permeation at the wound site. Nanoceria was also incorporated to enhance the antibacterial, antioxidant and wound healing properties of the fabricated nanoemulgel formulation. All the formulations were porous, hydrophilic, biodegradable, antioxidant, antibacterial, hemocompatible, biocompatible, and showed enhanced wound healing rate. The formulation (DG-SIS/Ce/NC) showed the highest free radicals scavenging capacity and antibacterial property with prolonged curcumin release (62.9% in 96 h), skin permeability (79.7% in 96 h); showed better cell growth under normal and oxidative-stressed conditions: it also showed full-thickness wound contraction (97.33% in 14 days) with highest collagen synthesis at the wound site (1.61 µg/mg in 14 days). The outcomes of this study suggested that the formulation (DG-SIS/Ce/NC) can be a potential nanoemulgel system for full-thickness wound healing application.


Assuntos
Curcumina , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Cério , Curcumina/farmacologia , Matriz Extracelular Descelularizada , Cicatrização
8.
Biomater Adv ; 136: 212783, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35929317

RESUMO

In this work, the magnetic α-Fe2O3/Fe3O4 heterogeneous nanotubes were successfully prepared by solvent hydrothermal-controlled calcination method. The effects of additive concentration, hydrothermal temperature and time on morphology of products were investigated. The α-Fe2O3/Fe3O4 nanotubes with a saturation magnetization of 50 emu/g were prepared calcinated at 600 °C for 4 h using 0.8 g of glucose. Their average length, the outer and inner diameters were around 240 nm, 178 nm and 145 nm, respectively. The α-Fe2O3/Fe3O4 heterogeneous nanotubes coated with water-soluble liposome were applied for targeted delivery of curcumin. The release of curcumin inside the hollow structure of the nanocomposites could be triggered and effectively sustained represented a process of slow release. The encapsulation efficiency of curcumin in the α-Fe2O3/Fe3O4-CUR@LIP nanocomposites reached 82.1 ± 0.9%. MTT assays demonstrated that blank carriers had excellent biocompatibility and application of magnetic field significantly elevated the cytotoxicity of α-Fe2O3/Fe3O4-CUR@LIP nanocomposites on MCF-7 cell. Electrochemical experiment and Prussian blue staining indicated that the α-Fe2O3/Fe3O4@LIP nanocomposites could aggregate in cells to promote the internalization of curcumin. Magnetic α-Fe2O3/Fe3O4-CUR@LIP nanocomposites and curcumin enhanced the expression of reactive oxygen species in MCF-7 cells and induced apoptosis by fluorescence detection. Flow cytometry and western blot verified that the α-Fe2O3/Fe3O4@LIP nanocomposites under magnetic field enhanced cells late-apoptosis by adjusting the expression of apoptosis-related proteins.


Assuntos
Curcumina , Nanotubos , Apoptose , Curcumina/farmacologia , Humanos , Células MCF-7 , Fenômenos Magnéticos
9.
Biomater Adv ; 139: 213040, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35914429

RESUMO

Curcumin (Cur) plays a key role in photodynamic antibacterial activity as a photosensitizer. On the other hand, the antimicrobial potential of graphene oxide (GO) has been reported controversially, and how to improve its antimicrobial ability has become an meaningful study. In this study, we prepared polydopamine-curcumin (PDA-Cur) by pi-pi stacking and loaded it onto the GO surface to obtain GO/PDA-Cur composite nanomaterials. GO/PDA-Cur was characterized by physical and optical means, and GO/PDA-Cur possessed good dispersion and stability in water. In vitro antibacterial results showed that GO/PDA-Cur mediated photodynamic therapy significantly reduced Gram-positive Staphylococcus aureus (S. aureus) by 4 orders of magnitude with a bactericidal rate of 99.99 %. The antibacterial mechanism stems from the fact that GO/PDA-Cur can generate reactive oxygen species (ROS) under white light irradiation (405-780 nm), which causes bacterial outer membrane breakage and cellular deformation. In addition, GO/PDA-Cur has good biocompatibility. The antibacterial ability of graphene oxide was significantly improved by combining it with PDA-Cur, which allows it to be used as a photodynamic antibacterial material.


Assuntos
Curcumina , Nanoestruturas , Antibacterianos/farmacologia , Curcumina/farmacologia , Grafite , Indóis , Polímeros , Staphylococcus aureus
10.
Molecules ; 27(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35807258

RESUMO

Previous research reported that the curcumin derivative (CU17) inhibited several cancer cell growths in vitro. However, its anticancer potential against human lung cancer cells (A549 cell lines) has not yet been evaluated. The purpose of this research was to examine the HDAC inhibitory and anti-cancer activities of CU17 compared to curcumin (CU) in A549 cells. An in vitro study showed that CU17 had greater HDAC inhibitory activity than CU. CU17 inhibited HDAC activity in a dose dependent manner with the half-maximal inhibitory concentration (IC50) value of 0.30 ± 0.086 µg/mL against HDAC enzymes from HeLa nuclear extract. In addition, CU17 could bind at the active pockets of both human class I HDACs (HDAC1, 2, 3, and 8) and class II HDACs (HDAC4, 6, and 7) demonstrated by molecular docking studies, and caused hyperacetylation of histone H3 (Ac-H3) in A549 cells shown by Western blot analysis. MTT assay indicated that both CU and CU17 suppressed A549 cell growth in a dose- and time-dependent manner. Besides, CU and CU17 induced G2/M phase cell cycle arrest and p53-independent apoptosis in A549 cells. Both CU and CU17 down-regulated the expression of p53, p21, Bcl-2, and pERK1/2, but up-regulated Bax expression in this cell line. Although CU17 inhibited the growth of lung cancer cells less effectively than CU, it showed less toxicity than CU for non-cancer cells. Accordingly, CU17 is a promising agent for lung cancer treatment. Additionally, CU17 synergized the antiproliferative activity of Gem in A549 cells, indicating the possibility of employing CU17 as an adjuvant treatment to enhance the chemotherapeutic effect of Gem in lung cancer.


Assuntos
Antineoplásicos , Curcumina , Neoplasias Pulmonares , Células A549 , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Cobre/farmacologia , Curcumina/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Simulação de Acoplamento Molecular , Proteína Supressora de Tumor p53
11.
Molecules ; 27(13)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35807304

RESUMO

Diabetes mellitus is a multifactorial chronic metabolic disorder, characterized by altered metabolism of macro-nutrients, such as fats, proteins, and carbohydrates. Diabetic retinopathy, diabetic cardiomyopathy, diabetic encephalopathy, diabetic periodontitis, and diabetic nephropathy are the prominent complications of diabetes. Inflammatory mediators are primarily responsible for these complications. Curcumin, a polyphenol derived from turmeric, is well known for its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. The regulation of several signaling pathways effectively targets inflammatory mediators in diabetes. Curcumin's anti-inflammatory and anti-oxidative activities against a wide range of molecular targets have been shown to have therapeutic potential for a variety of chronic inflammatory disorders, including diabetes. Curcumin's biological examination has shown that it is a powerful anti-oxidant that stops cells from growing by releasing active free thiol groups at the target location. Curcumin is a powerful anti-inflammatory agent that targets inflammatory mediators in diabetes, and its resistant form leads to better therapeutic outcomes in diabetes complications. Moreover, Curcumin is an anti-oxidant and NF-B inhibitor that may be useful in treating diabetes. Curcumin has been shown to inhibit diabetes-related enzymes, such as a-glucosidase, aldose reductase and aldose reductase inhibitors. Through its anti-oxidant and anti-inflammatory effects, and its suppression of vascular endothelial development and nuclear transcription factors, curcumin has the ability to prevent, or reduce, the course of diabetic retinopathy. Curcumin improves insulin sensitivity by suppressing phosphorylation of ERK/JNK in HG-induced insulin-resistant cells and strengthening the PI3K-AKT-GSK3B signaling pathway. In the present article, we aimed to discuss the anti-inflammatory mechanisms of curcumin in diabetes regulated by various molecular signaling pathways.


Assuntos
Curcumina , Diabetes Mellitus , Nefropatias Diabéticas , Aldeído Redutase , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes , Curcumina/farmacologia , Curcumina/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Humanos , Mediadores da Inflamação/metabolismo , Fosfatidilinositol 3-Quinases
12.
J Nanobiotechnology ; 20(1): 322, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836190

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective therapy and lack diagnosis strategy for preclinical AD patients. There is an urgent need for development of both early diagnosis and therapeutic intervention of AD. RESULTS: Herein, we developed a nanotheranostics platform consisting of Curcumin (Cur), an anti-inflammatory molecule, and superparamagnetic iron oxide (SPIO) nanoparticles encapsulated by diblock 1,2-dio-leoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)] (DSPE-PEG) that are modified with CRT and QSH peptides on its surface. Furthermore, we demonstrated that this multifunctional nanomaterial efficiently reduced ß-amyloid plaque burden specifically in APP/PS1 transgenic mice, with the process noninvasively detected by magnetic resonance imaging (MRI) and the two-dimensional MRI images were computed into three-dimension (3D) plot. Our data demonstrated highly sensitive in vivo detection of ß-amyloid plaques which more closely revealed real deposition of Aß than previously reported and we quantified the volumes of plaques for the first time based on 3D plot. In addition, memory deficits of the mice were significantly rescued, probably related to inhibition of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasomes. CONCLUSIONS: Gathered data demonstrated that this theranostic platform may have both early diagnostic and therapeutic potential in AD.


Assuntos
Doença de Alzheimer , Curcumina , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/química , Animais , Cognição , Curcumina/química , Curcumina/farmacologia , Curcumina/uso terapêutico , Modelos Animais de Doenças , Imageamento por Ressonância Magnética , Camundongos , Camundongos Transgênicos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Placa Amiloide/diagnóstico por imagem , Placa Amiloide/tratamento farmacológico , Nanomedicina Teranóstica
13.
Biomed Res Int ; 2022: 5886269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837379

RESUMO

Background: Breast cancer is one of the most common types of cancer diagnosed and the second leading cause of death among women. Breast cancer susceptibility proteins of type 1 and 2 are human tumor suppressor genes. Genetic variations/mutations in these two genes lead to overexpression of human breast tumor suppressor genes (e.g., BRCA1, BRCA2), which triggers uncontrolled duplication of cells in humans. In addition, multidrug resistance protein 1 (MDR1), an important cell membrane protein that pumps many foreign substances from cells, is also responsible for developing resistance to cancer chemotherapy. Aim of the Study. The aim of this study was to analyze some natural compounds or their derivatives as part of the development of strong inhibitors for breast cancer. Methodology. Molecular docking studies were performed using compounds known in the literature to be effective against BRCA1 and BRCA2 and MDR1, with positive control being 5-fluorouracil, an antineoplastic drug as a positive control. Results: The binding affinity of the compounds was analyzed, and it was observed that they had a better binding affinity for the target proteins than the standard drug 5-fluorouracil. Among the compounds analyzed, α-hederin, andrographolide, apigenin, asiatic acid, auricular acid, sinularin, curcumin, citrinin, hispolon, nerol, phytol, retinol palmitate, and sclareol showed the best binding affinity energy to the BRCA1, BRCA2, and MDR1 proteins, respectively. Conclusions: α-Hederin, andrographolide, apigenin, asiatic acid, auricular acid, hispolon, sclareol, curcumin, citrinin, and sinularin or their derivatives can be a good source of anticancer agents in breast cancer.


Assuntos
Neoplasias da Mama , Citrinina , Curcumina , Apigenina , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Curcumina/farmacologia , Feminino , Fluoruracila , Genes BRCA1 , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Simulação de Acoplamento Molecular
14.
Ann Parasitol ; 68(2): 263-273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35809560

RESUMO

Trichomonosis, caused by infection with a motile protozoan parasite called Trichomonas vaginalis, is the most common non-viral sexually transmitted disease worldwide. Since the 1960s, metronidazole has been used as a drug of choice. Considering increased resistance to anti-trichomonial drugs, alternative treatments are urgently needed. In this study, the standard strain of T. vaginalis was cultured in TYM medium. Curcumin and quercetin loaded with hyaluronic acid niosomes were prepared by the thin film hydration method. The mean vesicle size, polydispersity index, and zeta potential of each prepared formulation were characterized, and its anti-Trichomonas activity was assessed by concentrations of 0.01, 0.1, 1, 10 and 100 mg/ml. The cytotoxicity effects of the mentioned drugs were determined using a MTT assay on L929 fibroblast cell viability. The particle sizes of curcumin, quercetin, and curcumin-quercetin entrapped modified nano-niosomes were characterised as 243 ± 5.28, 223 ± 7.21 and 266 ± 4.81 nm. The results showed that quercetin and curcumin at a concentration of 100 mg/ml after 24 h had anti-T. vaginalis activity. However, curcumin at a concentration of 100 at time 3h with 97% growth inhibition had better performance than positive control (metronidazole). According to the results of the MTT assay, all drugs, even at the highest concentration (400 mg/ml), had no toxic effect on the fibroblast cell line. According to potent in vitro activity of curcumin and quercetin nanoniosomes against T. vaginalis in comparison with metronidazole, it can be concluded these compounds could be promising therapeutic candidates for trichomonosis in future.


Assuntos
Curcumina , Tricomoníase , Trichomonas vaginalis , Curcumina/farmacologia , Curcumina/uso terapêutico , Humanos , Lipossomos/farmacologia , Lipossomos/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Quercetina/farmacologia , Quercetina/uso terapêutico , Trichomonas vaginalis/fisiologia
15.
Molecules ; 27(14)2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35889538

RESUMO

A series of novel cobalt bis(dicarbollide)-curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained. In contrast to curcumin, the conjugates obtained were found to be non-cytotoxic against both tumor and normal cell lines. The analysis of the intracellular accumulation of the conjugates by flow cytometry showed that all cobalt bis(dicarbollide)-curcumin conjugates entered HCT116 colorectal carcinoma cells in a time-dependent manner. New non-cytotoxic conjugates contain a large amount of boron atoms in the biomolecule and can potentially be used for further biological research into boron neutron capture therapy (BNCT).


Assuntos
Terapia por Captura de Nêutron de Boro , Curcumina , Neoplasias , Boro/farmacologia , Compostos de Boro , Cobalto , Curcumina/farmacologia , Humanos
16.
Food Chem Toxicol ; 167: 113281, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35817260

RESUMO

Deoxynivalenol (DON) induces intestinal epithelial barrier disruption, posing a threat to the body. Curcumin (Cur) possesses pharmacological bioactivities such as antioxidant and anti-inflammatory effects that help maintain intestinal health. Here, the protective effects of Cur against DON-induced intestinal epithelial barrier disruption were explored. Cur (75 or 150 mg/kg body weight [B.W.]) alleviated DON-induced (2.4 mg/kg B.W.) inhibition of growth performance and morphological damage to intestinal epithelium in mice. Cur also significantly attenuated DON-induced intestinal epithelial barrier disruption and structural damage to the tight junctions (TJs), as assessed by ultrastructure observation, serum FITC-dextran concentrations and diamine oxidase activity. Cur mitigated the DON-induced increase in reactive oxygen species, malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels; p53, cytoplasmic cytochrome c, Bax, and Bcl-2 expression; and TUNEL-positive cell rate and caspase-3 activity. It decreased the total antioxidant capacity and expression of nuclear Nrf2 and its downstream target genes. Lastly, Cur attenuated the DON-induced increase in MLCK, p-MLC, nuclear NF-κB p65 expression, and the NF-κB downstream target genes; decrease in the expression of TJs proteins (claudin-1, occludin, and zonula occludens-1 [ZO-1]); and abnormal ZO-1 distribution. Overall, Cur mitigated the DON-induced disruption of the intestinal epithelial barrier by regulating the Nrf2/p53-mediated apoptotic pathway and NF-κB/MLCK-mediated TJs pathway in mice.


Assuntos
Curcumina , NF-kappa B , Animais , Antioxidantes/farmacologia , Curcumina/metabolismo , Curcumina/farmacologia , Mucosa Intestinal/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Junções Íntimas , Tricotecenos , Proteína Supressora de Tumor p53/metabolismo
17.
Tissue Cell ; 77: 101873, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35868051

RESUMO

Demyelination disease as diabetes mellitus (DM) complication is characterized by apoptosis of Schwann cells (SCs) and several reports have demonstrated that high glucose content can induce an inflammation response and lead to the apoptosis of SCs. For NF-κB plays a pivotal role in the inflammatory response, hence we hypothesized that high glucose content can induce inflammation though the NF-κB pathway. First we verified that 150 mM high glucose can increase the expression of cleaved caspase 3, interleukin (IL)- 1ß, Cyto-C and NF-κB with time through Western blot and increase the apoptosis of RSC96s through Flow Cytometry. Then we found that high glucose can increase the nuclear translocation NF-κB through confocal system which can promote the expression of inflammation genes such as IL-1ß. Curcumin has been reported to possess anti-inflammation activities to protect cells. In this study, we found that application with 25 µM curcumin could alleviate the inflammation response and protect the cells from apoptosis. We revealed that the expression of NF-κB and p-NF-κB was decreased and the translocation was also inhibited after curcumin application. Accordingly, the secretion of IL-1ß and the apoptosis of RSC96s induce by high glucose was suppressed. Our cumulative findings suggest that curcumin can protect SCs from apoptosis through the inhibition of the inflammatory response though the NF-κB pathway.


Assuntos
Curcumina , NF-kappa B , Apoptose , Curcumina/metabolismo , Curcumina/farmacologia , Glucose/metabolismo , Glucose/toxicidade , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , NF-kappa B/metabolismo , Células de Schwann/metabolismo , Transdução de Sinais
18.
Biomater Adv ; 139: 213017, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35882115

RESUMO

We herein fabricated a cancer nanotheranostics platform based on Graphene Oxide Quantum Dot-Chitosan-polyethylene glycol nanoconjugate (GOQD-CS-PEG), which were targeted with MUC-1 aptamer towards breast and colon tumors. The interaction between aptamer and MUC-1 receptor on the desired cells was investigated utilizing molecular docking. The process of curcumin release was investigated, as well as the potential of the produced nanocomposite in targeted drug delivery, specific detection, and photoluminescence imaging. The fluorescence intensity of GOQD-CS-PEG was reduced due to transferred energy between (cytosine-guanin) base pairs in the hairpin structure of the aptamer, resulting in an "on/off" photoluminescence bio-sensing. Interestingly, the integration of pH-responsive chitosan nanoparticles in the nanocomposite results in a smart nanocomposite capable of delivering more curcumin to desired tumor cells. When selectively binds to the MUC-1 receptor, the two strands of aptamer separate in acidic conditions, resulting in a sustained drug release and photoluminescence recovery. The cytotoxicity results also revealed that the nanocomposite was more toxic to MUC-1-overexpressed tumor cells than to negative control cell lines, confirming its selective targeting. As a result, the proposed nanocomposite could be used as an intelligent cancer nanotheranostic platform for tracing MUC-1-overexpressed tumor cells and targeting them with great efficiency and selectivity.


Assuntos
Quitosana , Curcumina , Neoplasias , Pontos Quânticos , Quitosana/química , Curcumina/farmacologia , Grafite , Humanos , Concentração de Íons de Hidrogênio , Simulação de Acoplamento Molecular , Pontos Quânticos/química , Nanomedicina Teranóstica
19.
Biomolecules ; 12(7)2022 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-35883488

RESUMO

The investigation of the usability of solid insoluble ß-cyclodextrin polymers (ßCDP) in micro-sized, controlled drug delivery systems has only recently attracted interest. Our aim was to form complexes with poorly soluble active pharmaceutical ingredients (APIs) with two types of ßCDP for drug delivery applications. Solid insoluble cyclodextrin polymer of irregular shape (ßCDPIS) and cyclodextrin microbeads (ßCDPB) were used in the experiments. Morphology, surface area, size distribution and swelling capacity of carriers were investigated. We created complexes with two APIs, curcumin and estradiol, and applied powder X-ray diffraction, FTIR and thermal analysis (TGA/DSC) to prove the complexation. Finally, the dissolution, biocompatibility and permeation of APIs on Caco-2 cells were investigated. The size of the beads was larger than 100 µm, their shape was spherical and surfaces were smooth; while the ßCDPIS particles were around 4 µm with irregular shape and surface. None of the polymers showed any cytotoxic effect on Caco-2 cells. Both carriers were able to extract curcumin and estradiol from aqueous solutions, and the dissolution test showed prolonged estradiol release. Caco-2 permeability tests were in accordance with the complexation abilities and dissolution of the complexes. This study offers useful data for further pharmaceutical applications of insoluble cyclodextrin polymers.


Assuntos
Curcumina , Ciclodextrinas , Células CACO-2 , Celulose , Curcumina/farmacologia , Portadores de Fármacos , Estradiol , Humanos , Microesferas , Polímeros , Solubilidade
20.
Biomater Adv ; 139: 212978, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35891599

RESUMO

The pharmacological effects of curcumin can be ascribed to its dose-dependent activity. Therapeutic application of curcumin is hindered by its poor solubility and low bioavailability. Carbon dots are gaining attention in biomedical applications in view of their unique photo-physical properties. Some carbon dots derived from bioactive molecules have shown superior activity than the parent compound. With an aim to address the limitations of curcumin, herein we compared the wound healing activity of curcumin-derived carbon dots (CurCD) with curcumin. The improved solubility and stability of CurCD, combined with its superior proliferative, proangiogenic and anti-bacterial activity suggested that CurCD would be more beneficial than curcumin in wound healing. To enable the sustained release of CurCD at the wound site, a protease-responsive hydrogel (GHCD) was prepared with CurCD acting as a cross-linker. A comparative study using a skin excision model revealed that GHCD supported faster wound closure with improved angiogenesis and complete restoration of the epithelium. Apart from the establishment of CurCD as a wound healing agent, the study provides a novel carbon dot based approach for molecules with limitations of solubility and bioavailability.


Assuntos
Curcumina , Carbono/farmacologia , Curcumina/farmacologia , Hidrogéis/farmacologia , Peptídeo Hidrolases/farmacologia , Cicatrização
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