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1.
Int J Mol Sci ; 22(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205035

RESUMO

Hyperpigmentation is a dermatological condition characterized by the overaccumulation and/or oversecretion of melanin pigment. The efficacy of curcumin as an anti-melanogenic therapeutic has been recognized, but the poor stability and solubility that have limited its use have inspired the synthesis of novel curcumin analogs. We have previously reported on comparisons of the anti-melanogenic activity of four novel chemically modified curcumin (CMC) analogs, CMC2.14, CMC2.5, CMC2.23 and CMC2.24, with that of parent curcumin (PC), using a B16F10 mouse melanoma cell model, and we have investigated mechanisms of inhibition. In the current study, we have extended our findings using normal human melanocytes from a darkly pigmented donor (HEMn-DP) and we have begun to study aspects of melanosome export to human keratinocytes. Our results showed that all the CMCs downregulated the protein levels of melanogenic paracrine mediators, endothelin-1 (ET-1) and adrenomedullin (ADM) in HaCaT cells and suppressed the phagocytosis of FluoSphere beads that are considered to be melanosome mimics. All the three CMCs were similarly potent (except CMC2.14, which was highly cytotoxic) in inhibiting melanin production; furthermore, they suppressed dendricity in HEMn-DP cells. CMC2.24 and CMC2.23 robustly suppressed cellular tyrosinase activity but did not alter tyrosinase protein levels, while CMC2.5 did not suppress tyrosinase activity but significantly downregulated tyrosinase protein levels, indicative of a distinctive mode of action for the two structurally related CMCs. Moreover, HEMn-DP cells treated with CMC2.24 or CMC2.23 partially recovered their suppressed tyrosinase activity after cessation of the treatment. All the three CMCs were nontoxic to human dermal fibroblasts while PC was highly cytotoxic. Our results provide a proof-of-principle for the novel use of the CMCs for skin depigmentation, since at low concentrations, ranging from 5 to 25 µM, the CMCs (CMC2.24, CMC2.23 and CMC2.5) were more potent anti-melanogenic agents than PC and tetrahydrocurcumin (THC), both of which were ineffective at melanogenesis at similar doses, as tested in HEMn-DP cells (with PC being highly toxic in dermal fibroblasts and keratinocytes). Further studies to evaluate the efficacy of CMCs in human skin tissue and in vivo studies are warranted.


Assuntos
Curcumina/farmacologia , Hiperpigmentação/tratamento farmacológico , Melaninas/biossíntese , Melanoma Experimental/tratamento farmacológico , Adrenomedulina/genética , Animais , Curcumina/análogos & derivados , Curcumina/química , Endotelina-1/genética , Humanos , Hiperpigmentação/metabolismo , Hiperpigmentação/patologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Melaninas/antagonistas & inibidores , Melanócitos/efeitos dos fármacos , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Melanossomas/efeitos dos fármacos , Melanossomas/genética , Camundongos , Fagocitose/genética , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia
2.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202905

RESUMO

Cereals are subject to contamination by pathogenic fungi, which damage grains and threaten public health with their mycotoxins. Fusarium graminearum and its mycotoxins, trichothecenes B (TCTBs), are especially targeted in this study. Recently, the increased public and political awareness concerning environmental issues tends to limit the use of traditional fungicides against these pathogens in favor of eco-friendlier alternatives. This study focuses on the development of biofungicides based on the encapsulation of a curcumin derivative, tetrahydrocurcumin (THC), in polysaccharide matrices. Starch octenylsuccinate (OSA-starch) and chitosan have been chosen since they are generally recognized as safe. THC has been successfully trapped into particles obtained through a spray-drying or freeze-drying processes. The particles present different properties, as revealed by visual observations and scanning electron microscopy. They are also different in terms of the amount and the release of encapsulated THC. Although freeze-dried OSA-starch has better trapped THC, it seems less able to protect the phenolic compound than spray-dried particles. Chitosan particles, both spray-dried and lyophilized, have shown promising antifungal properties. The IC50 of THC-loaded spray-dried chitosan particles is as low as 0.6 ± 0.3 g/L. These particles have also significantly decreased the accumulation of TCTBs by 39%.


Assuntos
Antifúngicos , Agentes de Controle Biológico , Quitosana , Fusarium/crescimento & desenvolvimento , Amido/análogos & derivados , Antifúngicos/química , Antifúngicos/farmacologia , Agentes de Controle Biológico/química , Agentes de Controle Biológico/farmacologia , Quitosana/química , Quitosana/farmacologia , Curcumina/análogos & derivados , Curcumina/química , Curcumina/farmacologia , Amido/química , Amido/farmacologia
3.
Food Chem ; 362: 130242, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34116430

RESUMO

Construction of nanoscale delivery systems from natural food biopolymer complexes have attracted increasing interests in the fields of food industries. In this study, novel carboxymethyl konjac glucomannan/ chitosan (CMKGM/CS) nanogels with and without 1-ethyl-3-(3-dimethylaminopropyl) /N-hydroxysuccinimide) (EDC/NHS)-initiated crosslinking were prepared. The physicochemical and structural properties of the CMKGM/CS nanogels and their potential to be a delivery vehicle for curcumin were investigated. Compared to original uncrosslinked nanogels, crosslinking did not alter particle size and morphology but decreased zeta potential of nanogels. Fourier transform infrared spectrum confirmed that the amide linkage was formed between CMKGM and CS, which obviously enhanced the stability of crosslinked nanogels under gastrointestinal conditions. Furthermore, the crosslinked nanogels not only had higher encapsulation efficiency of curcumin but also better sustained release behavior under simulated gastrointestinal conditions. These findings suggested that the crosslinked CMKGM/CS nanogels might be a promising delivery system for nutrients.


Assuntos
Quitosana/química , Curcumina/administração & dosagem , Curcumina/química , Sistemas de Liberação de Medicamentos/métodos , Mananas/química , Nanogéis/química , Tamanho da Partícula
4.
Molecules ; 26(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068636

RESUMO

The polyphenols curcumin (CU) and ferulic acid (FA) are able to inhibit the aggregation of amyloid-ß (Aß) peptide with different strengths. CU is a strong inhibitor while FA is a weaker one. In the present study, we examine the effects of CU and FA on the folding process of an Aß monomer by 1 µs molecular dynamics (MD) simulations. We found that both inhibitors increase the helical propensity and decrease the non-helical propensity of Aß peptide. They prevent the formation of a dense bulk core and shorten the average lifetime of intramolecular hydrogen bonds in Aß. CU makes more and longer-lived hydrogen bonds, hydrophobic, π-π, and cation-π interactions with Aß peptide than FA does, which is in a good agreement with the observed stronger inhibitory activity of CU on Aß aggregation.


Assuntos
Peptídeos beta-Amiloides/química , Ácidos Cumáricos/farmacologia , Curcumina/farmacologia , Dobramento de Proteína , Ácidos Cumáricos/química , Curcumina/química , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Dobramento de Proteína/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína , Solventes , Eletricidade Estática
5.
Int J Nanomedicine ; 16: 3555-3564, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079248

RESUMO

Purpose: A silver nanoparticle obtained by reducing salts with solid dispersion of curcumin (130 nm, 0.081 mg mL-1) was used to counteract against the toxic - edematogenic, myotoxic, and neurotoxic - effects of Philodryas olfersii venom. Methods: The edematogenic effect was evaluated by plasma extravasation in rat dorsal skin after injection of 50 µg per site of venom alone or preincubated with 1, 10, and 100 µL of AgNPs; the myotoxicity was evaluated by measuring the creatine kinase released into the organ-bath before the treatment and at the end of each experiment; and neurotoxicity was evaluated in chick biventer cervicis using the conventional myographic technique, face to the exogenous acetylcholine (ACh) and potassium chloride (KCl) added into the bath before the treatment and after each experiment. Preliminarily, a concentration-response curve of AgNPs was carried out to select the concentration to be used for neutralizing assays, which consists of neutralizing the venom-induced neuromuscular paralysis and edema by preincubating AgNPs with venom for 30 min. Results: The P. olfersii venom-induced edema (n=6) and a complete neuromuscular blockade (n=4) that includes the total and unrecovered block of ACh and KCl contractures. AgNPs produced a concentration-dependent decrease the venom-induced edema (n=6) from 223.3% to 134.4% and to 100.5% after 10 and 100 µL AgNPs-preincubation, respectively. The preincubation of venom with AgNPs (1 µL; n=6) was able to maintain 46.5 ± 10.9% of neuromuscular response under indirect stimuli, 39.2 ± 9.7% of extrinsic nicotinic receptors functioning in absence of electrical stimulus and 28.3 ± 8.1% of responsiveness to potassium on the sarcolemmal membrane. The CK release was not affected by any experimental protocol which was like control. Conclusion: AgNPs interact with constituents of P. olfersii venom responsible for the edema-forming activity and neuromuscular blockade, but not on the sarcolemma membrane-acting constituents. The protective effect of the studied AgNPs on avian preparation points out to molecular targets as intrinsic and extrinsic nicotinic receptors.


Assuntos
Colubridae , Nanopartículas Metálicas , Prata/química , Prata/farmacologia , Venenos de Serpentes/antagonistas & inibidores , Venenos de Serpentes/toxicidade , Animais , Galinhas , Creatina Quinase/metabolismo , Curcumina/química , Relação Dose-Resposta a Droga , Edema , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Neurotoxinas/antagonistas & inibidores , Neurotoxinas/toxicidade , Nervo Frênico/efeitos dos fármacos , Ratos
6.
Int J Nanomedicine ; 16: 4147-4159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168445

RESUMO

Purpose: To develop microchannel-based preparation of curcumin (Cur)-loaded hybrid nanoparticles using enzyme-targeted peptides and star-shaped polycyclic lipids as carriers, and to accomplish a desirable targeted drug delivery via these nanoparticles, which could improve the bioavailability and antitumor effects of Cur. Methods: The amphiphilic tri-chaintricarballylic acid-poly (ε-caprolactone)-methoxypolyethylene glycol (Tri-CL-mPEG) and the enzyme-targeted tetra-chain pentaerythritol-poly (ε-caprolactone)-polypeptide (PET-CL-P) were synthesized. The Cur-loaded enzyme-targeted hybrid nano-delivery systems (Cur-P-NPs) were prepared by using the microfluidic continuous granulation technology. The physicochemical properties, release behavior in vitro, and stability of these Cur-P-NPs were investigated. Their cytotoxicity, cellular uptake, anti-proliferative efficacy in vitro, biodistribution, and antitumor effects in vivo were also studied. Results: The particle size of the prepared Cur-P-NPs was 146.1 ± 1.940 nm, polydispersity index was 0.175 ± 0.014, zeta potential was 10.1 ± 0.300 mV, encapsulation rate was 74.66 ± 0.671%, and drug loading capacity was 5.38 ± 0.316%. The stability of Cur-P-NPs was adequate, and the in vitro release rate increased with the decrease of the environmental pH. Seven days post incubation, the cumulative release values of Cur were 52.78%, 67.39%, and 98.12% at pH 7.4, pH 6.8 and pH 5.0, respectively. Cur-P-NPs exhibited better cell entry and antiproliferation efficacy against U251 cells than the Cur-solution and Cur-NPs and were safe for use. Cur-P-NPs specifically targeted tumor tissues and inhibited their growth (78.63% tumor growth inhibition rate) with low toxic effects on normal tissues. Conclusion: The enzyme-targeted hybrid nanoparticles prepared in the study clearly have the tumor-targeting ability. Cur-P-NPs can effectively improve the bioavailability of Cur and have potential applications in drug delivery and tumor management.


Assuntos
Curcumina/química , Curcumina/farmacologia , Dispositivos Lab-On-A-Chip , Nanopartículas/química , Nanotecnologia/instrumentação , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Disponibilidade Biológica , Caproatos/química , Linhagem Celular Tumoral , Curcumina/farmacocinética , Portadores de Fármacos/química , Humanos , Lactonas/química , Camundongos , Tamanho da Partícula , Polietilenoglicóis/química , Distribuição Tecidual
7.
J Food Sci ; 86(6): 2242-2254, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33931881

RESUMO

The aim of the present study was to design a delivery system of curcumin (CU) loaded solid lipid nanoparticles (CU-CSLNs) for evaluating the antimicrobial properties in hamburger patty. Solid lipid nanoparticle (SLN) was prepared through a homogenizing technique. A response surface methodology was applied to optimize the CU-CSLNs to minimize the particle size (PS), polydispersity index (PDI), as well as to maximize the zeta potential to avoid aggregation of particles. The optimized sample revealed a spherical morphology under scanning electron microscope (SEM) and dynamic light scattering (DLS) with particle sizes of 126.87 ± 0.94 nm and 0.21 ± 0.025 PDI. The zeta potential and encapsulation efficiency (EE %) were found to be -30 ± 0.3 mV and 99.96 ± 0.01%, respectively. The CSLNs exhibited higher in vitro antimicrobial effect (142 µg·ml-1 ) against Staphylococcus aureus and generic Escherichia coli as compared to free CU (1000 µg·ml-1 ). Finally, the CSLNs antimicrobial effect was tested in hamburger patty inoculated with foodborne pathogens during eight days of storage at 4 °C. The results indicated that CSLNs had a higher antimicrobial effect than free CU. This study provides insight into the preparation of the novel antimicrobial nanoparticles for food safety applications.


Assuntos
Antibacterianos/farmacologia , Curcumina/farmacologia , Lipídeos/química , Produtos da Carne/microbiologia , Nanopartículas/química , Animais , Antibacterianos/química , Bovinos , Curcumina/química , Portadores de Fármacos , Escherichia coli/efeitos dos fármacos , Microbiologia de Alimentos , Tamanho da Partícula , Staphylococcus aureus/efeitos dos fármacos
8.
Food Chem ; 360: 130000, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33984567

RESUMO

Curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) - the class of natural compound derived from turmeric can exist as keto-enol and ß-diketone tautomer form. The structure and dynamics of particular relevance CUR is reported in prior studies, whereas DMC and BDMC, by far, have not been scrutinized. In the present studies, we have investigated the detailed molecular structure of CUR, DMC and BDMC by employing NMR spectroscopy as a key tool. The bridging carbon as methylene in ß-diketone form and methine in keto-enol form shows significant difference in NMR spectrum. The results justified that Curcuminoids (CC) has nearly 3% of ß-diketone tautomer in DMSO solvent at 298 K. Further, results revealed that ß-diketone form was favoured in alkaline pH condition whereas acidic and neutral pH conditions favour keto-enol tautomer. However, at higher temperature equilibrium shift towards ß-diketone tautomer. Moreover, this is the first report by NMR for observing the presence of ß-diketone tautomer.


Assuntos
Diarileptanoides/química , Cetonas/química , Cromatografia Líquida de Alta Pressão , Curcumina/química , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Conformação Molecular
9.
Food Chem ; 360: 129994, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33989877

RESUMO

The combinations of curcumin with green tea flavan-3-ols produce various synergistic biological effects. This study aimed to verify the antioxidant effects in mixtures of curcumin with (-)-epicatechin (EC) or with EC fraction from green tea in a non-polar lipid system (triacylglycerol autoxidation) and in a polar conditions (ABTS assay). Curcumin was 2.5-2.6 and 2.9-3.6 times weaker antioxidant than EC and EC fraction, respectively. The synergism was found in mixtures using the isobologram analysis of ABTS•+ scavenging activity results. The strongest effect with a combination index of 0.751 was in the equimolar mixture of pure compounds. In the lipid system, antagonism occurred for curcumin and EC fraction combination. However, an additive effect was found between curcumin and EC. In conclusion, the antioxidant effects in the curcumin and EC mixtures depended on the polarity of the assay media, the ratio of antioxidants, and presence other phenolics in the system.


Assuntos
Antioxidantes/química , Catequina/química , Curcumina/química , Chá/química , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Delgada , Sinergismo Farmacológico , Cinética , Extratos Vegetais/química , Estereoisomerismo , Chá/metabolismo
10.
Food Chem ; 361: 130117, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34058659

RESUMO

To overcome the poor water solubility of curcumin, a curcumin-ß-cyclodextrin (Cur-ß-CD) complex was prepared as a novel photosensitizer. Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to verify the formation of Cur-ß-CD. Furthermore, the ROS generation capacity and photodynamic bactericidal effect were measured to confirm this Cur-ß-CD complex kept photodynamic activity of curcumin. The result showed Cur-ß-CD could effectively generate ROS upon blue-light irradiation. The plate count assay demonstrated Cur-ß-CD complex possess desirable photodynamic antibacterial effect against food-borne pathogens including Staphylococcus aureus, Listeria monocytogenes and Escherichia coli. The cell morphology determined by scanning electron microscope (SEM) and transmission electron microscope (TEM) showed Cur-ß-CD could cause cell deformation, surface collapse and cell structure damage of the bacteria, resulting in the leakage of cytoplasmic; while agarose gel electrophoresis and SDS-PAGE further illustrated the inactivation mechanisms by Cur-ß-CD involve bacterial DNA damage and protein degradation.


Assuntos
Antibacterianos/química , Curcumina/química , Fármacos Fotossensibilizantes/química , beta-Ciclodextrinas/química , Antibacterianos/farmacologia , Varredura Diferencial de Calorimetria , Curcumina/farmacologia , Escherichia coli/efeitos dos fármacos , Luz , Listeria monocytogenes/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X , beta-Ciclodextrinas/farmacologia
11.
Acta Trop ; 220: 105945, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33945825

RESUMO

Schistosomiasis continues to pose significant public health problems in many developing countries. Mass drug administration (MDA) is the most adopted control option but there is increasing evidence for the development of praziquantel-resistant Schistosoma strains. This shortcoming has necessitated the search for other effective methods for the control of schistosomiasis. The breaking of Schistosoma transmission cycles through the application of molluscicides into snail infested freshwater bodies has yielded positive outcomes when integrated with MDA in some countries. However, few of such effective molluscicides are currently available, and where available, their application is restricted due to toxicity concerns. Some nanotized particles with molluscicidal activities against the different stages of snail intermediate hosts of schistosomes have been reported. Importantly, the curcumin-nisin nanoparticle synthesized by our group was very effective and it showed no significant toxicity in a mouse model and brine shrimps. This, therefore, offers the possibility of developing a molluscicide that is not only safe for man but also is environmentally friendly. This paper reviews nanoparticles with molluscicidal potential. The methods of their formulation, activities, probable mechanisms of actions, and their toxicity profiles are discussed. More research should be made in this field as it offers great potential for the development of new molluscicides.


Assuntos
Moluscocidas/química , Moluscocidas/farmacologia , Nanopartículas/química , Esquistossomose/transmissão , Caramujos/efeitos dos fármacos , Animais , Curcumina/química , Curcumina/farmacologia , Composição de Medicamentos , Humanos , Camundongos , Nisina/química , Nisina/farmacologia , Esquistossomose/prevenção & controle , Caramujos/fisiologia
12.
Food Chem ; 355: 129686, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33799264

RESUMO

In this study, core-shell biopolymer nanoparticles were fabricated for the encapsulation and delivery of curcumin using a pH-driven method. The influences of the coating composition on the physicochemical properties and curcumin release characteristics of the core-shell nanoparticles were studied. Fourier transform infrared spectroscopy and X-ray diffraction analyses indicated that curcumin was encapsulated in an amorphous state inside the nanoparticles. Particle size and ζ-potential measurements indicated that the biopolymer nanoparticles were relatively stable under different environmental conditions: long term storage, heating, pH changes and salt. The DPPH radical scavenging activity of the curcumin was increased after encapsulation within the nanoparticles, whereas the gastrointestinal release of curcumin was prolonged. These results were attributed to the ability of alginate and NaCas to form a thick layer around the nanoparticles, which increased the steric and electrostatic repulsion between them, as well as inhibiting the release of curcumin.


Assuntos
Alginatos/química , Fenômenos Químicos , Curcumina/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Nanopartículas/química , Zeína/química , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Eletricidade Estática
13.
Fish Shellfish Immunol ; 114: 65-81, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33895254

RESUMO

This study aimed to investigate the effectiveness of five natural plant extract compounds Curcumin (CUR); Eugenol (EUG), Cinnamaldehyde (CIN), Stigmasterol (ST) and Morin (MOR), on two species of Saprolegnia; Saprolegnia parasitica and S. australis. Selective compounds were screened for the minimum inhibitory concentration, first for anti-oomycetes activity and then mycelium growth inhibition, spore germination inhibition and colonisation test. Nitric oxide production and myeloperoxidase activity of the compounds were tested in head kidney leukocytes of rainbow trout, Oncorhynchus mykiss to assess the immunostimulatory potential. Molecular docking of effective compounds was carried out with effector proteins of S. parasitica to investigate the target binding sites. Among all, CUR could completely inhibit zoospore production and significantly (p ≤ .05) inhibit hyphal growth at 16 mg l-1 against S. parasitica and S. australis. CIN at the concentration of 50 mg l-1 completely inhibited hyphal growth of both Saprolegnia spp., although the zoospore production of S. parasitica and S. australis was reduced at 25 mg l-1 and 10 mg l-1. In the case of EUG, significant inhibition of the hyphal growth and germination of S. parasitica zoospores was observed at 50 mg l-1. ST and MOR did not show antioomycetes activity. The molecular docking results were consistent with in vitro studies, possibly due to the binding with the vital proteins (Plasma membrane ATPase, V-type proton ATPase, TKL protein kinase, Host targeting protein 1) of S. parasitica and ultimately inhibiting their activity. CUR and CIN showed increased nitric oxide production at the highest concentration of 250 and 256 mg l-1 but the value was not significant (p ≤ .05) with control. CUR showed significantly higher peroxidase activity (p ≤ .05) at a concentration of 256 mg l-1 though values were significantly similar with concentration from 16 to 128 mg l-1. The nitric oxide and total peroxidase activity of rainbow trout leukocytes in the case of CIN showed a significant difference only at 250 mg l-1 against the control. The results conclude that CUR, CIN showed the better anti-Saprolegnia activity and could be used as phyto-additives in aquaculture. Among all, the inclusion of CUR as phyto-additives will provide additional immunostimulatory activity.


Assuntos
Acroleína/análogos & derivados , Curcumina/farmacologia , Eugenol/farmacologia , Extratos Vegetais/farmacologia , Saprolegnia/efeitos dos fármacos , Acroleína/administração & dosagem , Acroleína/química , Acroleína/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Curcumina/química , Relação Dose-Resposta a Droga , Eugenol/química , Rim Cefálico/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Oncorhynchus mykiss , Extratos Vegetais/química
14.
Int J Mol Sci ; 22(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804997

RESUMO

Over the last years, different nanomaterials have been investigated to design highly selective and sensitive sensors, reaching nano/picomolar concentrations of biomolecules, which is crucial for medical sciences and the healthcare industry in order to assess physiological and metabolic parameters. The discovery of graphene (G) has unexpectedly impulsed research on developing cost-effective electrode materials owed to its unique physical and chemical properties, including high specific surface area, elevated carrier mobility, exceptional electrical and thermal conductivity, strong stiffness and strength combined with flexibility and optical transparency. G and its derivatives, including graphene oxide (GO) and reduced graphene oxide (rGO), are becoming an important class of nanomaterials in the area of optical and electrochemical sensors. The presence of oxygenated functional groups makes GO nanosheets amphiphilic, facilitating chemical functionalization. G-based nanomaterials can be easily combined with different types of inorganic nanoparticles, including metals and metal oxides, quantum dots, organic polymers, and biomolecules, to yield a wide range of nanocomposites with enhanced sensitivity for sensor applications. This review provides an overview of recent research on G-based nanocomposites for the detection of bioactive compounds, providing insights on the unique advantages offered by G and its derivatives. Their synthesis process, functionalization routes, and main properties are summarized, and the main challenges are also discussed. The antioxidants selected for this review are melatonin, gallic acid, tannic acid, resveratrol, oleuropein, hydroxytyrosol, tocopherol, ascorbic acid, and curcumin. They were chosen owed to their beneficial properties for human health, including antibiotic, antiviral, cardiovascular protector, anticancer, anti-inflammatory, cytoprotective, neuroprotective, antiageing, antidegenerative, and antiallergic capacity. The sensitivity and selectivity of G-based electrochemical and fluorescent sensors are also examined. Finally, the future outlook for the development of G-based sensors for this type of biocompounds is outlined.


Assuntos
Técnicas Biossensoriais , Condutividade Elétrica , Grafite/química , Antioxidantes/química , Ácido Ascórbico/química , Curcumina/química , Eletrodos , Radicais Livres , Ácido Gálico/química , Humanos , Glucosídeos Iridoides/química , Melatonina/química , Metais/química , Nanocompostos/química , Nanoestruturas/química , Óxidos/química , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , Pontos Quânticos , Resveratrol/química , Taninos/química , Tocoferóis/química
15.
Molecules ; 26(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806326

RESUMO

Recent evidence suggests that the formation of soluble amyloid ß (Aß) aggregates with high toxicity, such as oligomers and protofibrils, is a key event that causes Alzheimer's disease (AD). However, understanding the pathophysiological role of such soluble Aß aggregates in the brain in vivo could be difficult due to the lack of a clinically available method to detect, visualize, and quantify soluble Aß aggregates in the brain. We had synthesized a novel fluorinated curcumin derivative with a fixed keto form, named as Shiga-Y51, which exhibited high selectivity to Aß oligomers in vitro. In this study, we investigated the in vivo detection of Aß oligomers by fluorine-19 (19F) magnetic resonance imaging (MRI) using Shiga-Y51 in an APP/PS1 double transgenic mouse model of AD. Significantly high levels of 19F signals were detected in the upper forebrain region of APP/PS1 mice compared with wild-type mice. Moreover, the highest levels of Aß oligomers were detected in the upper forebrain region of APP/PS1 mice in enzyme-linked immunosorbent assay. These findings suggested that 19F-MRI using Shiga-Y51 detected Aß oligomers in the in vivo brain. Therefore, 19F-MRI using Shiga-Y51 with a 7 T MR scanner could be a powerful tool for imaging Aß oligomers in the brain.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/patologia , Curcumina/metabolismo , Modelos Animais de Doenças , Imagem por Ressonância Magnética de Flúor-19/métodos , Placa Amiloide/patologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/química , Animais , Encéfalo/metabolismo , Curcumina/química , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Placa Amiloide/metabolismo
16.
Molecules ; 26(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923340

RESUMO

Curcumin (CUR), a natural polyphenol extracted from rhizome of the Curcuma longa L, has received great attention for its multiple potential health benefits as well as disease prevention. For instance, CUR protects against toxic agents acting on the human body, including the nervous system. In detail, CUR possesses, among others, strong effects as an autophagy activator. The present study indicates that CUR counteracts methamphetamine (METH) toxicity. Such a drug of abuse is toxic by disturbing the autophagy machinery. We profited from an unbiased, low variable cell context by using rat pheochromocytoma PC12 cell line. In such a system, a strong protection was exerted by CUR against METH toxicity. This was associated with increased autophagy flux, merging of autophagosomes with lysosomes and replenishment of autophagy vacuoles with LC3, which instead is moved out from the vacuoles by METH. This is expected to enable the autophagy machinery. In fact, while in METH-treated cells the autophagy substrates α-synuclein accumulates in the cytosol, CUR speeds up α-synuclein clearance. Under the effects of CUR LC3 penetrate in autophagy vacuoles to commit them to cell clearance and promotes the autophagy flux. The present data provide evidence that CUR counteracts the neurotoxic effects induced by METH by promoting autophagy.


Assuntos
Curcumina/farmacologia , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Curcuma/química , Curcumina/química , Humanos , Metanfetamina/toxicidade , Fármacos Neuroprotetores/química , Síndromes Neurotóxicas/patologia , Células PC12 , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos
17.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805912

RESUMO

The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.


Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Suplementos Nutricionais , Inflamação/metabolismo , Obesidade/metabolismo , Termogênese , Adipogenia , Tecido Adiposo/metabolismo , Animais , Curcumina/química , Dieta , Retículo Endoplasmático/metabolismo , Ácidos Graxos Insaturados/metabolismo , Humanos , Resistência à Insulina , Intestinos/química , Lipídeos/química , Macrófagos/metabolismo , Polifenóis/química , Resveratrol/farmacologia , Transdução de Sinais
18.
Molecules ; 26(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919066

RESUMO

This study focuses on the role of photosensitizers in photodynamic therapy. The photosensitizers were prepared in combinations of 110/220 µM erythrosine and/or 10/20 µM demethoxy/bisdemethoxy curcumin with/without 10% (w/w) nano-titanium dioxide. Irradiation was performed with a dental blue light in the 395-480 nm wavelength range, with a power density of 3200 mW/cm2 and yield of 72 J/cm2. The production of ROS and hydroxyl radical was investigated using an electron paramagnetic resonance spectrometer for each individual photosensitizer or in photosensitizer combinations. Subsequently, a PrestoBlue® toxicity test of the gingival fibroblast cells was performed at 6 and 24 h on the eight highest ROS-generating photosensitizers containing curcumin derivatives and erythrosine 220 µM. Finally, the antifungal ability of 22 test photosensitizers, Candida albicans (ATCC 10231), were cultured in biofilm form at 37 °C for 48 h, then the colonies were counted in colony-forming units (CFU/mL) via the drop plate technique, and then the log reduction was calculated. The results showed that at 48 h the test photosensitizers could simultaneously produce both ROS types. All test photosensitizers demonstrated no toxicity on the fibroblast cells. In total, 18 test photosensitizers were able to inhibit Candida albicans similarly to nystatin. Conclusively, 20 µM bisdemethoxy curcumin + 220 µM erythrosine + 10% (w/w) nano-titanium dioxide exerted the highest inhibitory effect on Candida albicans.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Curcumina/química , Curcumina/farmacologia , Eritrosina/química , Fotoquimioterapia , Titânio/química , Antioxidantes/química , Antioxidantes/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Fibroblastos/metabolismo , Gengiva/citologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo
19.
Molecules ; 26(8)2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33920154

RESUMO

Cross-linked chitosan (CS) films with aldehyde groups obtained by oxidation of carboxymethyl cellulose (CMC) with NaIO4 were prepared using different molar ratios between the CHO groups from oxidized carboxymethyl cellulose (CMCOx) and NH2 groups from CS (from 0.25:1 to 2:1). Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy demonstrated the aldehyde groups' presence in the CMCOx. The maximum oxidation degree was 22.9%. In the hydrogel, the amino groups' conversion index value increased when the -CHO/-NH2 molar ratio, cross-linking temperature, and time increased, while the swelling degree values decreased. The hydrogel films were characterized by scanning electron microscopy (SEM) and FTIR analysis. The curcumin encapsulation efficiency decreases from 56.74% to 16.88% when the cross-linking degree increases. The immobilized curcumin release efficiency (REf%) and skin membrane permeability were evaluated in vitro in two different pH solutions using a Franz diffusion cell, and it was found to decrease when the molar ratio -CH=O/NH2 increases. The curcumin REf% in the receptor compartment was higher at pH = 7.4 (18%- for the sample with a molar ratio of 0.25:1) than at pH = 5.5 (16.5%). The curcumin absorption in the skin membrane at pH = 5.5 (47%) was more intense than at pH = 7.4 (8.6%). The curcumin-loaded films' antioxidant activity was improved due to the CS presence.


Assuntos
Celulose Oxidada/farmacologia , Quitosana/farmacologia , Curcumina/farmacologia , Dermatopatias/tratamento farmacológico , Animais , Carboximetilcelulose Sódica/química , Carboximetilcelulose Sódica/farmacologia , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Celulose Oxidada/química , Galinhas , Quitosana/química , Curcumina/química , Fármacos Dermatológicos/química , Fármacos Dermatológicos/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Dermatopatias/patologia , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Molecules ; 26(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806197

RESUMO

The acetylcholinesterase (AChE) inhibitors are the main drugs for symptomatic treatment of neurodegenerative disorders like Alzheimer's disease. A recently designed, synthesized and tested hybrid compound between the AChE inhibitor galantamine (GAL) and the antioxidant polyphenol curcumin (CU) showed high AChE inhibition in vitro. Here, we describe tests for acute and short-term toxicity in mice as well as antioxidant tests on brain homogenates measured the levels of malondialdehide (MDA) and glutathione (GSH) and in vitro DPPH, ABTS, FRAP and LPO inhibition assays. Hematological and serum biochemical analyses were also performed. In the acute toxicity tests, the novel AChE inhibitor given orally in mice showed LD50 of 49 mg/kg. The short-term administration of 2.5 and 5 mg/kg did not show toxicity. In the ex vivo tests, the GAL-CU hybrid performed better than GAL and CU themselves; in a dose of 5 mg/kg, it demonstrates 25% reduction in AChE activity, as well as a 28% and 73% increase in the levels of MDA and GSH, respectively. No significant changes in blood biochemical data were observed. The antioxidant activity of 4b measured ex vivo was proven in the in vitro tests. In the ABTS assay, 4b showed radical scavenging activity 10 times higher than the positive control butylhydroxy toluol (BHT). The GAL-CU hybrid is a novel non-toxic AChE inhibitor with high antioxidant activity which makes it a prospective multitarget drug candidate for treatment of neurodegenerative disorders.


Assuntos
Encéfalo/metabolismo , Inibidores da Colinesterase , Curcumina , Galantamina , Doenças Neurodegenerativas/tratamento farmacológico , Animais , Encéfalo/patologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Curcumina/análogos & derivados , Curcumina/química , Curcumina/farmacologia , Modelos Animais de Doenças , Feminino , Galantamina/análogos & derivados , Galantamina/química , Galantamina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia
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