RESUMO
BACKGROUND & AIMS: Turmeric (a source of curcumin) is an excellent food to modulate oxidative stress, inflammation, and gut dysbiosis in patients with chronic kidney disease (CKD). However, no studies report the benefits of curcumin in patients undergoing peritoneal dialysis (PD). This study aims to evaluate the effects of curcuminoid supplementation on oxidative stress, inflammatory markers, and uremic toxins originating from gut microbiota in patients with CKD undergoing PD. METHODS: This longitudinal, randomized, single-blind, placebo-controlled trial evaluated 48 patients who were randomized into two groups: Curcumin (three capsules of 500 mg of Curcuma longa extract, with 98.42 % total curcuminoids) or placebo (three capsules of 500 mg of starch) for twelve weeks. In the peripheral blood mononuclear cells (PBMCs), the transcriptional expression levels of Nrf2, HOX-1 and NF-κB were evaluated by quantitative real-time PCR. Oxidative stress was evaluated by malondialdehyde (MDA) and total Thiol (T-SH). TNF-α and IL-6 plasma levels were measured by ELISA. P-cresyl sulphate plasma level, a uremic toxin, was evaluated by high-performance liquid chromatography (HPLC) with fluorescent detection. RESULTS: Twenty-four patients finished the study: 10 in the curcumin group (57.5 ± 11.6 years) and 14 in the placebo group (56.5 ± 10.0 years). The plasma levels of MDA were reduced after 12 weeks in the curcumin group (p = 0.01), while the placebo group remained unchanged. However, regarding the difference between the groups at the endpoint, no change was observed in MDA. Still, there was a trend to reduce the p-CS plasma levels in the curcumin group compared to the placebo group (p = 0.07). Likewise, the concentrations of protein thiols, mRNA expression of Nrf2, HOX-1, NF-κB, and cytokines plasma levels did not show significant changes. CONCLUSION: Curcuminoid supplementation for twelve weeks attenuates lipid peroxidation and might reduce uremic toxin in patients with CKD undergoing PD. This study was registered on Clinicaltrials.gov as NCT04413266.
Assuntos
Curcumina , Diálise Peritoneal , Insuficiência Renal Crônica , Uremia , Humanos , Curcumina/farmacologia , Curcumina/uso terapêutico , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Leucócitos Mononucleares/metabolismo , Método Simples-Cego , Inflamação , Estresse Oxidativo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Diarileptanoides/farmacologia , Diarileptanoides/uso terapêutico , Suplementos Nutricionais , Uremia/tratamento farmacológicoRESUMO
The ability of mimicking the extracellular matrix architecture has gained electrospun scaffolds a prominent space into the tissue engineering field. The high surface-to-volume aspect ratio of nanofibers increases their bioactivity while enhancing the bonding strength with the host tissue. Over the years, numerous polyesters, such as poly(lactic acid) (PLA), have been consolidated as excellent matrices for biomedical applications. However, this class of polymers usually has a high hydrophobic character, which limits cell attachment and proliferation, and therefore decreases biological interactions. In this way, functionalization of polyester-based materials is often performed in order to modify their interfacial free energy and achieve more hydrophilic surfaces. Herein, we report the preparation, characterization, and in vitro assessment of electrospun PLA fibers with low contents (0.1 wt %) of different curcuminoids featuring π-conjugated systems, and a central ß-diketone unit, including curcumin itself. We evaluated the potential of these materials for photochemical and biomedical purposes. For this, we investigated their optical properties, water contact angle, and surface features while assessing their in vitro behavior using SH-SY5Y cells. Our results demonstrate the successful generation of homogeneous and defect-free fluorescent fibers, which are noncytotoxic, exhibit enhanced hydrophilicity, and as such greater cell adhesion and proliferation toward neuroblastoma cells. The unexpected tailoring of the scaffolds' interfacial free energy has been associated with the strong interactions between the PLA hydrophobic sites and the nonpolar groups from curcuminoids, which indicate its role for releasing hydrophilic sites from both parts. This investigation reveals a straightforward approach to produce photoluminescent 3D-scaffolds with enhanced biological properties by using a polymer that is essentially hydrophobic combined with the low contents of photoactive and multifunctional curcuminoids.
Assuntos
Diarileptanoides/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Diarileptanoides/farmacologia , Matriz Extracelular/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Varredura , Poliésteres/química , Espectroscopia de Prótons por Ressonância Magnética , Engenharia Tecidual/métodosRESUMO
The irrational use of medications has increased the incidence of microbial infections, which are a major threat to public health. Moreover, conventional therapeutic strategies are starting to become ineffective to treat these infections. Hence, there is a need to develop and characterize novel antimicrobial compounds. Phytochemicals are emerging as a safe and accessible alternative to conventional therapeutics for treating infectious diseases. Curcumin is extracted from the dried rhizome of the spice turmeric (Curcuma longa (Zingiberaceae)). However, the bioavailability of curcumin is low owing to its lipophilic property and thus has a low therapeutic efficacy in the host. A previous study synthesized structural variants of curcumin, which are called monocurcuminoids (CNs). CNs are synthesized based on the chemical structure of curcumin with only one methyl bridge. The biological activities of four previously synthesized CNs (CN59, CN63, CN67, and CN77), curcumin, and turmeric powder were examined in this study. Gas chromatography-tandem mass spectrometry analysis of curcumin and turmeric powder revealed similar peaks, which indicated the presence of curcumin in turmeric powder. The antioxidant activity of the test compounds was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays. The ABTS radical scavenging activities of the test compounds were similar to those of vitamin C. The minimum inhibitory concentration (MIC) values of the test compounds against seven microbial strains were in the range of 4.06-150⯵g/mL. The MIC value was equal to minimum bactericidal concentration value for CN63 (150⯵g/mL) and CN67 (120⯵g/mL) against Staphylococcus aureus. The treatment combination of CN77 (8.75 or 4.37⯵g/mL) and turmeric powder (9.37 or 4.68⯵g/mL) exerted synergistic growth-inhibiting effects on Aeromonas hydrophila, Candida albicans, and Pseudomonas aeruginosa. Photodynamic therapy using 2X MIC of CN59 decreased the growth of Enterococcus faecalis by 4.18-fold compared to the control group and completely inhibited the growth of Escherichia coli. The results of the hemolytic assay revealed that the test compounds were not cytotoxic with half-maximal inhibitory concentration values ranging from 49.65-130.9 µM. The anticoagulant activity of most compounds was comparable to that of warfarin but higher than that of heparin. This indicated that these compounds target the intrinsic coagulation pathway. These results demonstrated that these CNs are a safe and promising alternative for curcumin.
Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Bioprospecção , Candida albicans/efeitos dos fármacos , Diarileptanoides/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/toxicidade , Antioxidantes/síntese química , Antioxidantes/toxicidade , Bactérias/crescimento & desenvolvimento , Benzotiazóis/química , Compostos de Bifenilo/química , Coagulação Sanguínea/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Diarileptanoides/síntese química , Diarileptanoides/toxicidade , Resistência Microbiana a Medicamentos , Hemólise/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/toxicidade , Picratos/química , Carneiro Doméstico , Ácidos Sulfônicos/químicaRESUMO
The present study evaluated the anti-inflammatory effect of nanoencapsulated curcuminoid preparations of poly(vinyl pyrrolidone) (Nano-cur) and free curcuminoids (Cur) in an experimental model of croton oil-induced cutaneous inflammation. Male Swiss mice, weighing 25-30 g, received oral treatment by gavage 1 h before CO application or topical treatment immediately after CO application (200 µg diluted in 70% acetone) with a single dose of Cur and Nano-cur. After 6 h, the animals were anesthetized and euthanized. The ears were sectioned into disks (6.0 mm diameter) and used to determine edema, myeloperoxidase (MPO) activity, and oxidative stress. Photoacoustic spectroscopy (PAS) was used to evaluate the percutaneous penetration of Cur and Nano-cur. Topical treatment with both preparations had a similar inhibitory effect on the development of edema, MPO activity, and the oxidative response. The PAS technique showed that the percutaneous permeation of both topically applied preparations was similar. Oral Nano-cur administration exerted a higher anti-inflammatory effect than Cur. Topical Cur and Nano-cur application at the same dose similarly inhibited the inflammatory and oxidative responses. Oral Nano-cur administration inhibited such responses at doses that were eight times lower than Cur, suggesting the better bioavailability of Nano-cur compared with Cur.Graphical abstract.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Dermatite de Contato/tratamento farmacológico , Diarileptanoides/administração & dosagem , Fitoterapia/métodos , Pele/efeitos dos fármacos , Administração Oral , Administração Tópica , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Biomarcadores/metabolismo , Óleo de Cróton , Dermatite de Contato/etiologia , Dermatite de Contato/metabolismo , Dermatite de Contato/patologia , Diarileptanoides/farmacologia , Diarileptanoides/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Masculino , Camundongos , Nanocápsulas , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Pele/metabolismo , Pele/patologia , Resultado do TratamentoRESUMO
Curcumin, the most important secondary metabolite isolated from Curcuma longa, is known for its numerous purported therapeutic properties and as a natural dye. Herein, based on curcumin's intrinsic fluorescence, a search for improved curcumin-based fluorophores was conducted. Within the set of semi-synthetic curcumin derivatives i.e. mono (1), di (2), tri (3), tetra (4) benzylated and dibenzyl-fluoroborate (5), the fluorescence properties of 2 and 5 in solution outstood with a two-fold quantum yield compared to curcumin. Furthermore, all benzylated derivatives showed a favorable minimal cytotoxic activity upon screening at 25 µM against human cancer and non-tumoral COS-7 cell lines, with a reduction of its cytotoxic effect related to the degree of substitution. Fluorophores 2 and 5 are versatile bioimaging tools, as revealed by Confocal Fluorescence Microscopy (CFM), and showed permeation of living cell membranes of astrocytes and astrocytomas. When 2 is excited with a 405- (blue) or 543-nm (green) laser, it is possible to exclusively and intensively visualize the nucleus. However, the fluorescence emission fades as the laser wavelength moves towards the red region. In comparison, 5 allows selective visualization of cytoplasm when a 560-nm laser is used, showing emission in the NIR region, while it is possible to exclusively observe the nucleus at the blue region with a 405-nm laser.
Assuntos
Núcleo Celular , Citoplasma , Diarileptanoides/química , Diarileptanoides/farmacologia , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Imagem Molecular , Núcleo Celular/metabolismo , Curcumina/química , Curcumina/farmacologia , Citoplasma/metabolismo , Modelos Moleculares , Conformação Molecular , Imagem Molecular/métodos , Estrutura MolecularRESUMO
A facile protocol that enables synthetic interconversion of CUR-BF2 and CUR compounds is described that significantly widens the preparative scope of curcuminoids, providing access to larger libraries of compounds, thus enabling comparative antiproliferative and apoptotic study of a larger library of synthetic analogs in cancer cell lines.
Assuntos
Antineoplásicos/farmacologia , Diarileptanoides/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Diarileptanoides/síntese química , Diarileptanoides/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: Curcuminoids are known anti-inflammatory molecules with multiple mechanisms of action while adiponectin is an anti-inflammatory molecule secreted by the adipocytes. Curcuminoids may upregulate the expression of adiponectin and thus modulate their levels in serum. A meta-analysis was performed to identify randomized controlled trials evaluating the effect of curcuminoids on adiponectin concentrations. MATERIALS AND METHODS: The search included PubMed-Medline, Scopus, ISI Web of Science and Google Scholar databases (from inception to October 20, 2018) and the quality of studies was assessed according to Cochrane criteria. Quantitative data synthesis was conducted using a random-effects model and sensitivity analysis by the leave-one out method. Additional analysis was performed to assess the impact of potential confounders on adiponectin levels. RESULTS: The meta-analysis of five randomized clinical trials (n = 686) showed a significant elevation of plasma adiponectin concentrations following supplementation with curcuminoids (WMD: 6.47 ng/mL, 95% CI: 1.85, 11.10, p = 0.010; I2 = 94.85%). The effect size was robust in the leave-one-out sensitivity analysis and the effect size was not driven by a single study in the meta-analysis. CONCLUSION: This meta-analysis showed a significant increase in plasma levels of adiponectin following curcuminoids therapy, which may be one of the mechanisms of anti-inflammatory activity of curcumin.
Assuntos
Adiponectina/metabolismo , Anti-Inflamatórios/farmacologia , Diarileptanoides/farmacologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Crohn's Disease (CD) and Ulcerative Colitis (UC) result from an overreaction of the bowel to multifactorial stimuli leading to discomfort, pain, and it is associated with high morbidity and lethality. The medications commonly used are expensive and associated with multiple side effects. Curcuma longa exerts anti-inflammatory and antioxidant actions and has shown positive effects on CD and UC treatment, possibly due to the presence of curcuminoids. The objective of this review was to evaluate the role of curcuminoids in the treatment of IBD. A search for articles associating curcuminoids and CD and UC was performed using MEDLINE-PubMed. It has been found that curcumin can reduce oxidative stress and inhibit the migration of neutrophils and inducible nitric oxide synthase in the intestine. It may also improve micro and macroscopic lesions, prevent apoptosis of intestinal cells and also induce the restoration of the mitogen-activated protein kinase immune reaction. As the incidence of CD and UC is growing in many populations, there is an urgency to find an appropriate and accessible therapeutic approach to improve quality of life of patients. The use of curcumin is cheap, efficient and associated with no side effects, and may become an alternative to the IBD treatment.
Assuntos
Adjuvantes Imunológicos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Curcuma/química , Diarileptanoides/uso terapêutico , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/uso terapêutico , Bases de Dados Factuais , Diarileptanoides/farmacologia , Humanos , Neutrófilos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Qualidade de VidaRESUMO
Propolis is commercialized in Chile as an antimicrobial agent. It is obtained mainly from central and southern Chile, but is used for the same purposes regardless of its origin. To compare the antimicrobial effect, the total phenolic (TP), the total flavonoid (TF) content and the phenolic composition, 19 samples were collected in the main production centers in the Región del Maule, Chile. Samples were extracted with MeOH and assessed for antimicrobial activity against Gram (+) and Gram (-) bacteria. TP and TF content, antioxidant activity by the DPPH, FRAP and TEAC methods were also determined. Sample composition was assessed by HPLD-DAD-ESI-MS/MS. Differential compounds in the samples were isolated and characterized. The antimicrobial effect of the samples showed MICs ranging from 31.5 to > 1000 µg/mL. Propolis from the central valley was more effective as antibacterial than those from the coastal area or Andean slopes. The samples considered of interest (MIC ≤ 62.5 µg/mL) showed effect on Escherichia coli, Pseudomonas sp., Yersinia enterocolitica and Salmonella enteritidis. Two new diarylheptanoids, a diterpene, the flavonoids pinocembrin and chrysin were isolated and elucidated by spectroscopic and spectrometric means. Some 29 compounds were dereplicated by HPLC-MS and tentatively identified, including nine flavones/flavonol derivatives, one flavanone, eight dihydroflavonols and nine phenyl-propanoids. Propolis from the Región del Maule showed large variation in antimicrobial effect, antioxidant activity and composition. So far the presence of diarylheptanoids in samples from the coastal area of central Chile can be considered as a marker of a new type of propolis.
Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/análise , Própole/química , Antibacterianos/química , Antioxidantes/química , Chile , Cromatografia Líquida de Alta Pressão , Diarileptanoides/química , Diarileptanoides/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
The activity of several diarylheptanoid derivatives (curcuminoids) was previously evaluated against Leishmania amazonensis promastigotes and among them the most active compound was 5-hydroxy-7- (4-hydroxy-3-methoxyphenyl)-1-(4-methoxyphenyl)-1,4,6-heptatrien-3-one. This study was carried out to investigate the influence of this diaryl derivative on the infective promastigotes and Balb/c mice peritoneal macrophage interaction. The potential in vitro toxicity was also evaluated. Promastigotes pretreated for 24 hours with the compound had their infective capacity significantly decreased. When the infection of Balb/c macrophage by L. amazonensis promastigotes was already installed, addition of the drug resulted in a diminishing of the infection rate. It was demonstrated that the compound was not toxic to the host macrophage in a concentration equivalent to the LD50/24h from the previous in vitro experiment.