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1.
Synapse ; 79(1): e70008, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39748146

RESUMO

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.


Assuntos
Envelhecimento , Curcumina , Hipocampo , Fármacos Neuroprotetores , Ratos Wistar , Vanadatos , Animais , Curcumina/farmacologia , Fármacos Neuroprotetores/farmacologia , Vanadatos/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ratos , Masculino , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
2.
J Nutr Biochem ; 135: 109768, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39278425

RESUMO

Inflammation is a common feature of neurological disorders that alters cell function in microglia and astrocytes as well as other neuronal cell types. Astrocytes modulate blood flow, regulate glutamate metabolism, and exert antioxidant protection. When responding to inflammatory damage, astrocytes enhance immune cell infiltration and amplify inflammatory responses via the upregulation of cytokine production. Several molecules have been proposed to attenuate neuroinflammation and control neurological diseases. Curcumin gained attention due to its capacity to cross the blood-brain barrier and its well-described anti-inflammatory and antioxidant activities. Our study aimed to understand if oral curcumin administration could protect against central nervous system inflammatory damage induced by intracerebroventricular injection of LPS while focusing on astrocyte function. Despite its poor bioavailability, we found that curcumin reaches the central nervous system, prevents the locomotory damage caused by LPS, and reduces inflammatory signaling via IL-1ß and COX-2. Furthermore, we observed that curcumin was protective against LPS-induced S100B secretion in the cerebrospinal fluid and GSH reduction in the hippocampal tissue. However, curcumin could not protect the animals from anhedonia, assessed by the sucrose preference test, and weight loss induced by LPS. Our results indicate that oral curcumin administration exerts a protective anti-inflammatory action in the central nervous system, attenuating the sickness behavior induced by ICV LPS. This work demonstrates that curcumin has an important modulative effect on astrocytes, thus suggesting that astrocytes are critical to the anti-inflammatory effects of curcumin.


Assuntos
Astrócitos , Curcumina , Lipopolissacarídeos , Doenças Neuroinflamatórias , Subunidade beta da Proteína Ligante de Cálcio S100 , Animais , Curcumina/farmacologia , Lipopolissacarídeos/toxicidade , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Masculino , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Interleucina-1beta/metabolismo , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Anedonia/efeitos dos fármacos
3.
Food Microbiol ; 125: 104645, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39448155

RESUMO

This study assessed the SARS-CoV-2 surrogate bacteriophage φ6 cross-contamination between high-density polyethylene or polyvinyl chloride gloves and fruits (tomato and cucumber) using different inoculum levels (6.0 and 4.0 log PFU/sample). Bacteriophage φ6 survival on contaminated gloves was assessed over 9 days at 25 °C. The effectiveness of photodynamic treatment using curcumin as a photosensitizer to inactivate φ6 on fruits was determined. The fruit type and the glove material influenced the φ6 transfer. Longer contact times resulted in greater φ6 transfer. The highest φ6 transfer occurred from tomato to HDPE glove (0.8% or -1.1 log % transfer) after 30 s of contact at the higher inoculum level. Bacteriophage φ6 was detected on cross-contaminated HDPE gloves for up to 6 days. Bacteriophage φ6 survived better on vinyl gloves cross-contaminated by cucumber vs. tomato (detected up to 6 vs 3 days). Photodynamic inactivation of φ6 was time-dependent and varied with the tested fruit but was not influenced by viral starting concentration. Photodynamic treatment decreased the φ6 titer by 3.0 and 2.2 log PFU/sample in tomato and cucumber, respectively. Transmission electronic microscopy showed that photodynamic treatment changed the structure of the φ6 capsid. These findings may help in the management of SARS-CoV-2 contamination risks in fruit handling. They may also help in the establishment of effective measures to manage cross-contamination risk.


Assuntos
Bacteriófago phi 6 , COVID-19 , Cucumis sativus , Frutas , Fármacos Fotossensibilizantes , SARS-CoV-2 , Solanum lycopersicum , SARS-CoV-2/efeitos dos fármacos , Frutas/virologia , Solanum lycopersicum/virologia , COVID-19/virologia , Bacteriófago phi 6/efeitos dos fármacos , Bacteriófago phi 6/fisiologia , Bacteriófago phi 6/crescimento & desenvolvimento , Cucumis sativus/virologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Inativação de Vírus/efeitos dos fármacos , Inativação de Vírus/efeitos da radiação , Luvas Protetoras , Humanos , Curcumina/farmacologia , Curcumina/química
4.
Braz Oral Res ; 38: e123, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39661796

RESUMO

Curcumin, found in turmeric rhizomes (Curcuma longa L.), has been widely studied for its potential health benefits, including anti-inflammatory, antioxidant, and wound-healing properties. However, due to its low bioavailability and unfavorable pharmacokinetics, analogous compounds have been developed to obtain better biopharmaceutical characteristics and enhanced biological effects. In this study, we evaluated the activity of curcumin and three of its synthetic analogues (DMAD, DMAM, and RI75) on the viability and differentiation of a pre-osteoblastic cell line (MC3T3-E1). We also assessed the expression of key genes involved in tissue regeneration: vascular endothelial growth factor (vegf), stromal-derived growth factor 1 (SDF-1/CXCL12), and runt-related transcription factor 2 (runx2). The cells were treated with curcumin and the three analogues at concentrations of 10, 30, or 50 µM. All tested analogues and curcumin exhibited moderate to no cell toxicity compared to the cells treated under standard conditions across all concentrations after 24, 48, and 72 hours. Only the RI75 analogue showed upregulation of SDF-1, a crucial factor in tissue regeneration. Compared to curcumin, the DMAM and RI75 analogues also upregulated runx2 and vegf, both associated with osteodifferentiation. The RI75 analogue demonstrated greater mineralization than curcumin, and both promoted more nodule formation than the untreated control. Our data suggest that the curcumin analogue RI75 at 50 µM presents similar toxicity but enhanced biological activity compared to natural curcumin, making it a promising substance for material biomodifications.


Assuntos
Diferenciação Celular , Sobrevivência Celular , Subunidade alfa 1 de Fator de Ligação ao Core , Curcumina , Osteoblastos , Fator A de Crescimento do Endotélio Vascular , Curcumina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Osteoblastos/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Camundongos , Fatores de Tempo , Expressão Gênica/efeitos dos fármacos , Quimiocina CXCL12 , Reprodutibilidade dos Testes , Linhagem Celular , Análise de Variância , Reação em Cadeia da Polimerase em Tempo Real
5.
PLoS Negl Trop Dis ; 18(11): e0012637, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39531489

RESUMO

BACKGROUND: Sporotrichosis is a zoonotic disease caused by the dimorphic fungus Sporothrix spp., leading to skin lesions that can, in some cases, progress and result in the death of infected individuals. Candida albicans is another fungus involved in several skin, oral, and vaginal mucosal infections. Fungal diseases are concerning due to increasing incidence and the limited variety of antifungal classes available for treatment. Furthermore, antifungal medications can cause various side effects, exacerbated by their prolonged use during infection treatment. There is a need to explore alternatives to conventional drugs that are effective, fast, and safe in combating sporotrichosis. This study aimed to achieve in vitro elimination of the fungi Sporothrix brasiliensis and Sporothrix schenckii through Photodynamic Inactivation (PDI), using curcumin as a photosensitizer and in combination with antifungal agents used in the treatment of sporotrichosis. METHODOLOGY: Yeasts of Candida albicans, Sporothrix brasiliensis, and Sporothrix schenckii were subjected to Photodynamic Inactivation (PDI) using light at a wavelength of 450 ± 10 nm, irradiance of 35 mW/cm2, delivering a fluence of 31.5 J/cm2, with curcumin as the photosensitizer at doses ranging from 0.75 to 150 µg/mL. After determining the Minimum Inhibitory Concentration (MIC) values of the antifungal drugs itraconazole, ketoconazole, and potassium iodide, sub-MIC doses of these antifungals were combined with sub-MIC doses of curcumin in a new PDI session. CONCLUSION: Photodynamic inactivation is a promising technique in the treatment of sporotrichosis, as well as its combination with antifungals. The combination of curcumin in concentrations ranging from 0.75 g/mL a 7.5 g/mL with sub-MIC concentrations of itraconazole, ketoconazole, and potassium iodide was able to completely inactivate the fungi C. albicans, S. brasiliensis and S. schenckii, indicating that PDI may increase the effectiveness of antifungals. However, further studies are needed to establish protocols for future clinical applications.


Assuntos
Antifúngicos , Candida albicans , Curcumina , Fármacos Fotossensibilizantes , Sporothrix , Sporothrix/efeitos dos fármacos , Sporothrix/efeitos da radiação , Candida albicans/efeitos dos fármacos , Candida albicans/efeitos da radiação , Antifúngicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Curcumina/farmacologia , Fotoquimioterapia/métodos , Testes de Sensibilidade Microbiana , Humanos , Esporotricose/tratamento farmacológico , Esporotricose/microbiologia
6.
J Appl Oral Sci ; 32: e20240251, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39570178

RESUMO

OBJECTIVE: Diabetes mellitus (DM) delays wound healing, including those following tooth extractions. Curcumin (CCM) can promote soft tissue and bone healing. The present study investigates the healing effects of CCM on tooth extraction sockets in diabetic rats. METHODOLOGY: Ninety-six male Wistar rats were divided into the following four groups: Control+Corn Oil (CO), Control+CCM, DM+CO, and DM+CCM. Each group was subdivided into 7-, 14-, and 28-day time point subgroups comprising eight rats. All animals had their maxillary first molars extracted. CCM-treated rats received 100 mg/kg of CCM orally for 7, 14, and 28 days. The lesion area was evaluated using macroscopic analyses, whereas socket healing was assessed by hematoxylin and eosin staining. Keratinocyte growth factor (KGF), Runt-related transcription factor 2 (Runx2), and collagen type I (COL1) expression levels were obtained using quantitative polymerase chain reaction (qPCR). Bone healing was analyzed by means of microcomputed tomography (µCT). RESULTS: After 7 days, the groups showed no significant differences in lesion area and by day 14, no lesions were present. CCM treatment increased KGF mRNA expression in diabetic rats; however, diabetic rats showed delayed bone healing unrelated to CCM. CCM treatment resulted in increased Runx2 mRNA expression only in control rats, whereas COL1 mRNA expression remained unaffected by CCM. CONCLUSION: CCM shows potential as a soft tissue healing enhancer in diabetic rats and could serve as an additional treatment to promote soft tissue repair in diabetic individuals. Although CCM did not impact alveolar bone healing, it may enhance bone healing in other skeleton regions.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core , Curcumina , Diabetes Mellitus Experimental , Ratos Wistar , Extração Dentária , Alvéolo Dental , Cicatrização , Microtomografia por Raio-X , Animais , Alvéolo Dental/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Masculino , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Subunidade alfa 1 de Fator de Ligação ao Core/análise , Curcumina/farmacologia , Fatores de Tempo , Colágeno Tipo I/análise , Reprodutibilidade dos Testes , Resultado do Tratamento , Reação em Cadeia da Polimerase em Tempo Real , Distribuição Aleatória
7.
Sci Rep ; 14(1): 28268, 2024 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-39550440

RESUMO

Antimicrobial resistance is a growing threat to global public health, requiring innovative approaches for its control. Photodynamic inactivation (PDI) with light-activated photosensitizers has emerged as a strategy to combat resistant bacteria, challenging the intrinsic heterogeneity of bacterial populations. This study evaluates the impact of PDI on both heterogeneity and shape of the distribution profile of resistant bacterial populations, specifically on strains of Staphylococcus aureus resistant to amoxicillin, erythromycin, and gentamicin, for exploring its potential as an adjuvant therapy in the fight against bacterial resistance. Curcumin (10 µM) was used as a photosensitizer and five cycles of PDI were applied on Staphylococcus aureus strains under 450 nm irradiation of 10 J/cm² energy density. The resistance variations amongst bacterial subpopulations were investigated by calculating the minimum inhibitory concentration (MIC) before and after PDI treatment. MIC was significantly reduced by the antibiotics tested post-PDI and a reduction in the heterogeneity of bacterial populations was recorded, suggesting PDI can effectively decrease the resistance diversity of Staphylococcus aureus. The result reinforces the potential of PDI as a valuable adjuvant therapy, offering a promising avenue for mitigating bacterial resistance and promoting more effective treatment strategies against resistant infections.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes , Staphylococcus aureus , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/efeitos da radiação , Fármacos Fotossensibilizantes/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Curcumina/farmacologia , Fotoquimioterapia/métodos , Eritromicina/farmacologia , Luz
8.
Int J Mol Sci ; 25(21)2024 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-39519045

RESUMO

Breast cancer is a public health concern worldwide, characterized by increasing incidence and mortality rates, requiring novel and effective therapeutic strategies. Curcumin is a bioactive compound extracted from turmeric with several pharmacological activities. Curcumin is a multifaceted anticancer agent through mechanisms including the modulation of signaling pathways, inhibition of cell proliferation, induction of apoptosis, and production of reactive oxygen species. However, the poor water solubility and bioavailability of curcumin create important barriers in its clinical application. This review elaborates on the therapeutic potential of curcumin in breast cancer treatment, focusing on the efficacy of different administration routes and synergistic effects with other therapeutic agents. The intravenous administration of curcumin-loaded nanoparticles significantly improves bioavailability and therapeutic outcomes compared to oral routes. Innovative formulations, such as nano-emulsifying drug delivery systems, have shown promise in enhancing oral bioavailability. While intravenous delivery ensures higher bioavailability and direct action on tumor cells, it is more invasive and expensive than oral administration. Advancing research on curcumin in breast cancer treatment is essential for improving therapeutic outcomes and enhancing the quality of life of patients.


Assuntos
Neoplasias da Mama , Curcumina , Curcumina/uso terapêutico , Curcumina/administração & dosagem , Curcumina/farmacologia , Curcumina/farmacocinética , Curcumina/química , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Animais , Disponibilidade Biológica , Vias de Administração de Medicamentos , Nanopartículas/química , Administração Oral , Sistemas de Liberação de Medicamentos/métodos
9.
Microb Pathog ; 197: 107079, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39454803

RESUMO

Bacteria coordinate gene expression in a cell density-dependent manner using a communication process called quorum sensing (QS). The expression of virulence factors, biofilm formation and enzyme production are examples of QS-regulated phenotypes that can interfere with food quality and safety. Due to the importance of these phenotypes, the inhibition of bacterial communication as an anti-virulence strategy is of great interest. This work aimed to evaluate the effect of phenolic compounds on the inhibition of biofilm formation by Pseudomonas aeruginosa PAO1, using concentrations that do not interfere in bacterial growth. The synergistic effect of rosmarinic acid, baicalein, curcumin and resveratrol with tobramycin and between the phenolics themselves was evaluated. The tested combinations proved to be a good strategy for reducing the dose of antibiotics used in treatments and obtaining satisfactory results against P. aeruginosa biofilms. The combination of the four compounds at the highest concentration (500 µM) completely inhibited biofilm formation. The obtained results contribute to understanding the effect of phenolic compounds on QS inhibition, which may help to define the mechanism of inhibition, in addition to expanding the biotechnological potential of these compounds for future applications in the food, pharmaceutical and medical fields.


Assuntos
Antibacterianos , Biofilmes , Depsídeos , Sinergismo Farmacológico , Flavanonas , Fenóis , Pseudomonas aeruginosa , Percepção de Quorum , Resveratrol , Ácido Rosmarínico , Tobramicina , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Pseudomonas aeruginosa/efeitos dos fármacos , Tobramicina/farmacologia , Antibacterianos/farmacologia , Percepção de Quorum/efeitos dos fármacos , Fenóis/farmacologia , Depsídeos/farmacologia , Resveratrol/farmacologia , Flavanonas/farmacologia , Curcumina/farmacologia , Cinamatos/farmacologia , Testes de Sensibilidade Microbiana , Fatores de Virulência
10.
Int J Biol Macromol ; 281(Pt 4): 136650, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39419161

RESUMO

The traditional treatment of colorectal cancer (CRC) involves a combination of chemotherapy and synthetic and natural drugs. In this study, a hybrid compound of 5-fluorouracil-curcumin encapsulated in bacterial nanocellulose (BNC) was evaluated for CRC treatment. Bacterial nanocellulose was produced using K. medellinensis and spray-dried. The encapsulation technique involved solvent evaporation. The interactions between cellulose and the hybrid were evaluated using adsorption isotherms and kinetics, and the system was morphologically and physiochemically characterized. The capsules were tested in vitro using Dukes' C and B CRC cells. The results indicated heterogeneous and incomplete adsorption of the hybrid onto the active sites of cellulose. Capsules with a BNC:hybrid mass ratio of 1:1 maintained the encapsulant properties while maximizing the drug load according to desorption in simulated stomach and colon fluids, where desorption in the colon was 1.79 times greater than that in the stomach. Finally, the cancer cell inhibition results indicated that the encapsulated hybrid performed better on Dukes' C-stage cells than on Duke's B-stage cells. In this study, a new system based on a hybrid cellulose compound was proposed for CRC treatment, specifically for metastatic CRC.


Assuntos
Celulose , Neoplasias Colorretais , Curcumina , Fluoruracila , Celulose/química , Fluoruracila/farmacologia , Fluoruracila/química , Curcumina/química , Curcumina/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Humanos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Nanopartículas/química , Cápsulas , Adsorção
11.
Biomolecules ; 14(10)2024 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-39456228

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is a challenging childhood cancer to treat, with limited therapeutic options and high relapse rates. This study explores deamidated triosephosphate isomerase (dTPI) as a novel therapeutic target. We hypothesized that selectively inhibiting dTPI could reduce T-ALL cell viability without affecting normal T lymphocytes. Computational modeling and recombinant enzyme assays revealed that disulfiram (DS) and curcumin (CU) selectively bind and inhibit dTPI activity without affecting the non-deamidated enzyme. At the cellular level, treatment with DS and CU significantly reduced Jurkat T-ALL cell viability and endogenous TPI enzymatic activity, with no effect on normal T lymphocytes, whereas the combination of sodium dichloroacetate (DCA) with DS or CU showed synergistic effects. Furthermore, we demonstrated that dTPI was present and accumulated only in Jurkat cells, confirming our hypothesis. Finally, flow cytometry confirmed apoptosis in Jurkat cells after treatment with DS and CU or their combination with DCA. These findings strongly suggest that targeting dTPI represents a promising and selective target for T-ALL therapy.


Assuntos
Curcumina , Ácido Dicloroacético , Dissulfiram , Sinergismo Farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Triose-Fosfato Isomerase , Humanos , Células Jurkat , Triose-Fosfato Isomerase/antagonistas & inibidores , Triose-Fosfato Isomerase/metabolismo , Dissulfiram/farmacologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Curcumina/farmacologia , Curcumina/análogos & derivados , Ácido Dicloroacético/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química
12.
Cell Biochem Funct ; 42(7): e4119, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39244707

RESUMO

In the present study, we investigated whether curcumin administration would interfere with the main renal features of l-NAME-induced hypertension model. For this purpose, we conducted both in vitro and in vivo experiments to evaluate renal indicators of inflammation, oxidative stress, and metalloproteinases (MMPs) expression/activity. Hypertension was induced by l-NAME (70 mg/kg/day), and Wistar rats from both control and hypertensive groups were treated with curcumin (50 or 100 mg/kg/day; gavage) or vehicle for 14 days. Blood and kidneys were collected to determine serum creatinine levels, histological alterations, oxidative stress, MMPs expression and activity, and ED1 expression. l-NAME increased blood pressure, but both doses of curcumin treatment reduced these values. l-NAME treatment increased creatinine levels, glomeruli area, Bowman's space, kidney MMP-2 activity, as well as MMP-9 and ED1 expression, and reduced the number of glomeruli. Curcumin treatment prevented the increase in creatinine levels, MMP-2 activity, and reduced MMP-2, MMP-9, ED1, and superoxide levels, as well as increased superoxide dismutase activity and partially prevented glomeruli alterations. Moreover, curcumin directly inhibited MMP-2 activity in vitro. Thus, our main findings demonstrate that curcumin reduced l-NAME-induced hypertension and renal glomerular alterations, inhibited MMP-2 and MMP-9 expression/activity, and reduced oxidative stress and inflammatory processes, which may indirectly impact hypertension-induced renal outcomes.


Assuntos
Curcumina , Hipertensão , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , NG-Nitroarginina Metil Éster , Animais , Masculino , Ratos , Curcumina/farmacologia , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Nefropatias/patologia , Nefropatias/metabolismo , Nefropatias/tratamento farmacológico , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar
13.
Braz J Med Biol Res ; 57: e13550, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39258670

RESUMO

Emerging evidence demonstrates that curcumin has an inhibitory effect on non-small cell lung cancer (NSCLC), and its targets and mechanism of action need further exploration. The goal of this study was to explore the potential targets and mechanism of curcumin against NSCLC by network pharmacology, bioinformatics, and experimental validation, thereby providing more insight into combination treatment with curcumin for NSCLC in preclinical and clinical research. Curcumin targets against NSCLC were predicted based on HIT2.0, STD, CTD, and DisGeNET, and the core targets were analyzed via protein-protein interaction network construction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and molecular docking. The gene expression levels of samples in A549 cells, NCI-H460, and curcumin treated groups were detected by real-time quantitative PCR. A total of 67 common targets between curcumin and NSCLC were collected by screening public databases. GO and KEGG analysis suggested that curcumin treatment of NSCLC mainly involves cancer-related pathways, such as PI3K-AKT signaling pathway, Foxo signaling pathway, microRNAs, MAPK signaling pathway, HIF-1 signaling pathway, etc. The targets with the highest degree were identified through the PPI network, namely CASP3, CTNNB1, JUN, IL6, MAPK3, HIF1A, STAT3, AKT1, TP53, CCND1, VEGFA, and EGFR. The results of the in vitro experiments showed that curcumin treatment of NSCLC down-regulated the gene expressions of CCND1, CASP3, HIF1A, IL-6, MAPK3, STAT3, AKT1, and TP53. Our findings revealed that curcumin functions as a potential therapeutic candidate for NSCLC by suppressing multiple signaling pathways and interacting with multiple gene targets.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Biologia Computacional , Curcumina , Neoplasias Pulmonares , Simulação de Acoplamento Molecular , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Curcumina/farmacologia , Curcumina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mapas de Interação de Proteínas/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real
14.
Int J Biol Macromol ; 278(Pt 3): 134887, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39168194

RESUMO

This study aimed to develop mucoadhesive chitosan-based films capable of enhancing the curcumin penetration into the oral mucosa to treat oral cancers. We developed three films containing medium molecular weight chitosan (190-310 KDa) and other excipients (polyvinyl alcohol, Poloxamer®407, and propylene glycol) that have proven to be compatible with each other and with curcumin in thermal analyses. The films were smooth, flexible, and precipitates free, with uniform weight and thickness, pH compatible with the oral mucosa, resistance to traction, and entrapped curcumin in a high proportion. They also exhibited necessary swelling and mucoadhesion for tissue adherence. Ex vivo penetration studies proved that the films significantly increased the penetration of curcumin into the oral mucosa compared to control, even when the mucosa was subjected to a condition of simulated salivation. Curcumin exhibited cytotoxic activity in vitro in the two head and neck cancer cell lines (FaDu, SCC-9) at doses close to those found in penetration studies with the films. When combined with radiotherapy, curcumin demonstrated superiority over single doses of radiotherapy at 4, 8, and 12 Gy. Therefore, the developed films may represent a promising alternative for the topical treatment of oral tumors.


Assuntos
Quitosana , Curcumina , Mucosa Bucal , Neoplasias Bucais , Curcumina/química , Curcumina/farmacologia , Curcumina/administração & dosagem , Quitosana/química , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Humanos , Linhagem Celular Tumoral , Mucosa Bucal/metabolismo , Mucosa Bucal/efeitos dos fármacos , Animais , Administração Tópica , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Adesividade
15.
Biomolecules ; 14(7)2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39062565

RESUMO

(1) Introduction: Curcumin and Lippia origanoides essential oils have a broad spectrum of biological activities; however, their physicochemical instability, low solubility, and high volatility limit their therapeutic use. Encapsulation in liposomes has been reported as a feasible approach to increase the physicochemical stability of active substances, protect them from interactions with the environment, modulate their release, reduce their volatility, improve their bioactivity, and reduce their toxicity. To date, there are no reports on the co-encapsulation of curcumin and Lippia origanoides essential oils in liposomes. Therefore, the objective of this work is to prepare and physiochemical characterize liposomes loaded with the mixture of these compounds and to evaluate different in vitro biological activities. (2) Methods: Liposomes were produced using the thin-layer method and physiochemical characteristics were calculated. The antimicrobial and cytotoxic activities of both encapsulated and non-encapsulated compounds were evaluated. (3) Results: Empty and loaded nanometric-sized liposomes were obtained that are monodisperse and have a negative zeta potential. They inhibited the growth of Staphylococcus aureus and did not exhibit cytotoxic activity against mammalian cells. (4) Conclusions: Encapsulation in liposomes was demonstrated to be a promising strategy for natural compounds possessing antimicrobial activity.


Assuntos
Curcumina , Lipossomos , Lippia , Óleos Voláteis , Staphylococcus aureus , Lipossomos/química , Curcumina/química , Curcumina/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Lippia/química , Humanos , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacos , Tamanho da Partícula
16.
J Biophotonics ; 17(9): e202400190, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39021314

RESUMO

Candida albicans biofilm can cause diseases that are resistant to conventional antifungal agents. Photodynamic (PDI), sonodynamic (SDI), and sonophotodynamic (SPDI) inactivation have arisen as promising antimicrobial strategies. This study evaluated these treatments mediated by curcumin against C. albicans biofilms. For this, C. albicans biofilms were submitted to PDI, SDI, or SPDI with different light and ultrasound doses, then, the viability assay was performed to measure the effectiveness. Finally, a mathematical model was suggested to fit acquired experimental data and understand the synergistic effect of light and ultrasound in different conditions. The results showed that SPDI, PDI, and SDI reduced the viability in 6 ± 1; 1 ± 1; and 2 ± 1 log, respectively, using light at 60 J/cm2, ultrasound at 3 W/cm2, and 80 µM of curcumin. The viability reduction was proportional to the ultrasound and light doses delivered. These results encourage the use of SPDI for the control of microbial biofilm.


Assuntos
Biofilmes , Candida albicans , Curcumina , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Curcumina/farmacologia , Viabilidade Microbiana/efeitos dos fármacos , Luz , Ondas Ultrassônicas , Fármacos Fotossensibilizantes/farmacologia , Fotoquimioterapia
17.
Poult Sci ; 103(10): 104022, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39068694

RESUMO

The maternal diet and egg incubation temperature are some of the factors that can influence the embryonic development and performance of the newly chicks at 15 d of age. This study evaluated the effects of adding a blend of organic acids, essential oils, curcumin, tannins, vitamin E, and zinc microencapsulated in to the diet of female quails (Coturnix coturnix japonica) on their productive, reproductive performance and redox parameters of their eggs and the interaction of maternal diet × incubation temperature on embryo (E16 and E18) and chicks development. At 98 d of age, 64 female quails with a mean body weight of 150 g ± 0.5 were distributed into two treatments: a Basal diet or a diet supplemented with blend (Sannimix). The eggs from each female were incubated at 37.5°C (Control) and 38.5°C (High Temperature) throughout the incubation period. After hatching, chicks were distributed in a 2 (maternal diet) × 2 (incubation temperature) factorial design. Female quails supplemented with Sannimix showed better productive and reproductive performance and produced higher-quality embryos. Their offspring had greater weight at hatch and at 15 d of age. The eggs and offspring of supplemented with Sannimix female quails showed better oxidative stability. At E16 and E18, High Temperature increased yolk sac utilization and gene expression of the growth hormone receptor (GHR). At E16, embryos from supplemented with Sannimix female quail had higher expression of insulin-like growth factor type I (IGFI) and heat shock protein 70 kDa genes. At 15 d of age, highest expression of the GHR and IGFI genes was observed in chicks from female quails fed the Sannimix diet, regardless of incubation temperature. Regarding the maternal diet × incubation temperature an improved result was observed for chicks from female quails fed with Sannimix even when eggs are exposed to High Temperature during the incubation. The supplementation of quail diets with blend Sannimix improves productive and reproductive performance, egg quality and their embryos, as well as their offspring quality.


Assuntos
Ração Animal , Coturnix , Curcumina , Dieta , Suplementos Nutricionais , Óleos Voláteis , Vitamina E , Zinco , Animais , Ração Animal/análise , Dieta/veterinária , Feminino , Suplementos Nutricionais/análise , Coturnix/crescimento & desenvolvimento , Óleos Voláteis/administração & dosagem , Vitamina E/administração & dosagem , Zinco/administração & dosagem , Zinco/metabolismo , Curcumina/administração & dosagem , Curcumina/farmacologia , Taninos/administração & dosagem , Temperatura , Reprodução/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos
18.
Dalton Trans ; 53(47): 18902-18916, 2024 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-38938129

RESUMO

Palladium(II) complexes have stimulated research interest mainly due to their in vitro cytotoxicity against various cancer cell lines and their low cytotoxicity in healthy cells. Thus, in this work, we combined Pd(II)/phosphine systems with the natural product curcumin as a ligand, obtaining a series of complexes, [Pd(cur)(PPh3)2]PF6 (A1), [Pd(cur)(dppe)]PF6 (A2), [Pd(cur)(dppp)]PF6 (A3), [Pd(cur)(dppb)]PF6 (A4) and [Pd(cur)(dppf)]PF6 (A5), where dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, dppb = 1,4-bis(diphenylphosphino)butane, and dppf = 1,1'-bis(diphenylphosphino)ferrocene (P-P), which were characterized by elemental analysis, molar conductivity analysis, and mass, NMR (1H, 13C, 31P{1H}), UV-vis, and IR spectroscopies, and four of them (A1, A2, A4, and A5) by X-ray crystallography. The in vitro cell viability of the complexes A1-A5, cisplatin, and the free ligand curcumin against MDA-MB-231 (human triple-negative breast tumor cells), SK-BR-3 (human breast tumor cells), A549 (human lung tumor cells), MRC-5 (non-tumor human lung cells), A2780 (human ovarian carcinoma cells), and A2780cis (cisplatin-resistant human ovarian carcinoma cells), was evaluated by the MTT colorimetric assay. For the tumor cell lines tested, the complexes showed good anticancer activities. The results showed that in general the complexes had lower IC50 values than free curcumin and the precursors [PdCl2(P-P)]. IC50 results obtained for the A1-A5 complexes, in the MCF-7 cell line, are similar to those that had already been observed for some Pd/bipy/curcumin complexes. In the MDA-MB-231 cell line, complexes A1 and A5 stood out, with their lowest IC50 values, around 5 µmol L-1, and the complexes appeared to be more active (lower IC50 values) against the ovarian cell lines. Complex A1 was 23 and 22-fold more cytotoxic than cisplatin, against the A2780 and A2780cis cells, respectively. The complex A1 was studied on A2780cis cells and it was found that this complex inhibits colony formation and induces cell cycle arrest in the sub-G1 phase in a concentration-dependent manner and leads to cell death by apoptosis. The DCFDA assay revealed a potent ROS induction for complex A1.


Assuntos
Antineoplásicos , Complexos de Coordenação , Curcumina , Ensaios de Seleção de Medicamentos Antitumorais , Paládio , Fosfinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Curcumina/farmacologia , Curcumina/química , Paládio/química , Paládio/farmacologia , Fosfinas/química , Fosfinas/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estrutura Molecular
19.
Nanomedicine (Lond) ; 19(15): 1407-1423, 2024 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-38920352

RESUMO

Aim: To investigate the effect of surfactant type on curcumin-loaded (CUR) PLGA nanoparticles (NPs) to modulate monocyte functions. Materials & methods: The nanoprecipitation method was used, and PLGA NPs were designed using Pluronic F127 (F127) and/or lecithin (LEC) as surfactants. Results: The Z-average of the NPs was <200 nm, they had a spherical shape, Derjaguin-Muller-Toporov modulus >0.128 MPa, they were stable during storage at 4°C, ζ-potential ∼-40 mV, polydispersity index <0.26 and % EE of CUR >94%. PLGA-LEC/F127 NPs showed favorable physicochemical and nanomechanical properties. These NPs were bound and internalized mainly by monocytes, suppressed monocyte-induced reactive oxygen species production, and decreased the ability of monocytes to modulate T-cell proliferation. Conclusion: These results demonstrate the potential of these NPs for targeted therapy.


This study explores how different surfactants affect curcumin-loaded PLGA nanoparticles, a biodegradable polymer. The nanoparticles were designed using Pluronic F127 and/or lecithin as surfactants. They are less than 200 nm and spherical. They are stable when stored at 4 °C, with a surface charge of about -40 mV, and can encapsulate more than 94% of curcumin.The results of this study are promising, showing that PLGA nanoparticles using a mixture of lecithin and Pluronic F127 as surfactants have favorable properties toward monocyte adhesion. They are primarily taken up by monocytes, a type of white blood cell, and demonstrate a remarkable ability to reduce the production of reactive oxygen species, which can cause cell damage, as well as the ability of monocytes to stimulate the proliferation of T cells. This underscores the potential of these nanoparticles in targeted therapy, particularly in diseases where monocytes play a pivotal role, such as chronic inflammatory conditions.


Assuntos
Curcumina , Lecitinas , Monócitos , Nanopartículas , Poloxâmero , Humanos , Proliferação de Células/efeitos dos fármacos , Curcumina/química , Curcumina/farmacologia , Portadores de Fármacos/química , Lecitinas/química , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Nanopartículas/química , Tamanho da Partícula , Poloxâmero/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Espécies Reativas de Oxigênio/metabolismo , Tensoativos/química , Linfócitos T/efeitos dos fármacos
20.
Jpn J Infect Dis ; 77(5): 260-268, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-38825455

RESUMO

Biofilm-producing methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (MR-CoNS) pose clinical challenges in treating healthcare-associated infections. As alternative antimicrobial options are needed, in this study, we aimed to determine the effect of curcumin-chitosan magnetic nanoparticles (Cur-Chi-MNP) on the biofilms of staphylococcal clinical isolates. MRSA and CoNS clinical isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing was performed using the broth microdilutions. Nanoparticles were synthesized by the co-precipitation of magnetic nanoparticles (MNP) and encapsulated by the ionotropic gelation of curcumin (Cur) and chitosan (Chi). Biofilm inhibition and eradication by nanoparticles, with and without the addition of oxacillin (OXA), were assessed in Staphylococcus strains. Cur-Chi-MNP showed antimicrobial activity against planktonic cells of MRSA and MR-CoNS strains and inhibited MRSA biofilm. The addition of OXA to Cur-Chi-MNP increased the biofilm inhibition and eradication activity against all staphylococcal strains (P = 0.0007), and higher biofilm activity was observed in the early biofilm stages. Cur-Chi-MNP showed antimicrobial and biofilm inhibitory activities against S. aureus. Addition of OXA increased biofilm inhibition and eradication activity against all staphylococcal strains. A combination treatment of Cur-Chi-MNP and OXA could potentially be used to treat staphylococcal biofilm-associated infections in the early stages before the establishment of biofilm bacterial cells.


Assuntos
Antibacterianos , Biofilmes , Quitosana , Curcumina , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Biofilmes/efeitos dos fármacos , Quitosana/farmacologia , Quitosana/química , Curcumina/farmacologia , Antibacterianos/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Nanopartículas de Magnetita/química , Oxacilina/farmacologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/fisiologia
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