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1.
Int J Mol Sci ; 25(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38474103

RESUMO

Maize ranks as the second most widely produced crop globally, yielding approximately 1.2 billion tons, with corn cob being its primary byproduct, constituting 18 kg per 100 kg of corn. Agricultural corn production generates bioactive polysaccharide-rich byproducts, including xylan (Xyl). In this study, we used the redox method to modify corn cob xylan with gallic acid, aiming to enhance its antioxidant and protective capacity against oxidative stress. The conjugation process resulted in a new molecule termed conjugated xylan-gallic acid (Xyl-GA), exhibiting notable improvements in various antioxidant parameters, including total antioxidant capacity (1.4-fold increase), reducing power (1.2-fold increase), hydroxyl radical scavenging (1.6-fold increase), and cupric chelation (27.5-fold increase) when compared with unmodified Xyl. At a concentration of 1 mg/mL, Xyl-GA demonstrated no cytotoxicity, significantly increased fibroblast cell viability (approximately 80%), and effectively mitigated intracellular ROS levels (reduced by 100%) following oxidative damage induced by H2O2. Furthermore, Xyl-GA exhibited non-toxicity toward zebrafish embryos, offered protection against H2O2-induced stress, and reduced the rate of cells undergoing apoptosis resulting from H2O2 exposure. In conclusion, our findings suggest that Xyl-GA possesses potential therapeutic value in addressing oxidative stress-related disturbances. Further investigations are warranted to elucidate the molecular structure of this novel compound and establish correlations with its pharmacological activities.


Assuntos
Antioxidantes , Ácido Gálico , Animais , Antioxidantes/farmacologia , Ácido Gálico/farmacologia , Xilanos/farmacologia , Zea mays/metabolismo , Peróxido de Hidrogênio/farmacologia , Peixe-Zebra/metabolismo , Estresse Oxidativo
2.
Mar Drugs ; 21(7)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37504919

RESUMO

A blend refers to the combination of two or more components to achieve properties that are superior to those found in the individual products used for their production. Gracilaria birdiae agaran (SPGb) and chromium picolinate (ChrPic) are both antioxidant agents. However, there is no documentation of blends that incorporate agarans and ChrPic. Hence, the objective of this study was to generate blends containing SPGb and ChrPic that exhibit enhanced antioxidant activity compared to SPGb or ChrPic alone. ChrPic was commercially acquired, while SPGb was extracted from the seaweed. Five blends (B1; B2; B3; B4; B5) were produced, and tests indicated B5 as the best antioxidant blend. B5 was not cytotoxic or genotoxic. H2O2 (0.6 mM) induced toxicity in fibroblasts (3T3), and this effect was abolished by B5 (0.05 mg·mL-1); neither ChrPic nor SPGb showed this effect. The cells also showed no signs of toxicity when exposed to H2O2 after being incubated with B5 and ChrPic for 24 h. In another experiment, cells were incubated with H2O2 and later exposed to SPGb, ChrPic, or B5. Again, SPGb was not effective, while cells exposed to ChrPic and B5 reduced MTT by 100%. The data demonstrated that B5 has activity superior to SPGb and ChrPic and points to B5 as a product to be used in future in vivo tests to confirm its antioxidant action. It may also be indicated as a possible nutraceutical agent.


Assuntos
Gracilaria , Rodófitas , Alga Marinha , Antioxidantes/farmacologia , Peróxido de Hidrogênio/farmacologia , Verduras
3.
Mar Drugs ; 21(11)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37999381

RESUMO

Fucans from marine algae have been the object of many studies that demonstrated a broad spectrum of biological activities, including anti-inflammatory effects. The aim of this study was to verify the protective effects of a fucan extracted from the brown algae Spatoglossum schröederi in animals submitted to a generalized inflammation model induced by zymosan (ZIGI). BALB/c mice were first submitted to zymosan-induced peritonitis to evaluate the treatment dose capable of inhibiting the induced cellular migration in a simple model of inflammation. Mice were treated by the intravenous route with three doses (20, 10, and 5 mg/kg) of our fucan and, 1 h later, were inoculated with an intraperitoneal dose of zymosan (40 mg/kg). Peritoneal exudate was collected 24 h later for the evaluation of leukocyte migration. Doses of the fucan of Spatoglossum schröederi at 20 and 10 mg/kg reduced peritoneal cellular migration and were selected to perform ZIGI experiments. In the ZIGI model, treatment was administered 1 h before and 6 h after the zymosan inoculation (500 mg/kg). Treatments and challenges were administered via intravenous and intraperitoneal routes, respectively. Systemic toxicity was assessed 6 h after inoculation, based on three clinical signs (bristly hair, prostration, and diarrhea). The peritoneal exudate was collected to assess cellular migration and IL-6 levels, while blood samples were collected to determine IL-6, ALT, and AST levels. Liver tissue was collected for histopathological analysis. In another experimental series, weight loss was evaluated for 15 days after zymosan inoculation and fucan treatment. The fucan treatment did not present any effect on ZIGI systemic toxicity; however, a fucan dose of 20 mg/kg was capable of reducing the weight loss in treated mice. The treatment with both doses also reduced the cellular migration and reduced IL-6 levels in peritoneal exudate and serum in doses of 20 and 10 mg/kg, respectively. They also presented a protective effect in the liver, with a reduction in hepatic transaminase levels in both doses of treatment and attenuated histological damage in the liver at a dose of 10 mg/kg. Fucan from S. schröederi presented a promising pharmacological activity upon the murine model of ZIGI, with potential anti-inflammatory and hepatic protective effects, and should be the target of profound and elucidative studies.


Assuntos
Peritonite , Phaeophyceae , Camundongos , Animais , Zimosan/toxicidade , Interleucina-6 , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Ascite , Redução de Peso
4.
Int J Mol Sci ; 24(21)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37958868

RESUMO

Oxidative stress has been associated with different diseases, and different medicinal plants have been used to treat or prevent this condition. The leaf ethanolic extract (EE) and aqueous extract (AE) from Coccoloba alnifolia have previously been characterized to have antioxidant potential in vitro and in vivo. In this study, we worked with EE and AE and two partition phases, AF (ethyl acetate) and BF (butanol), from AE extract. These extracts and partition phases did not display cytotoxicity. The EE and AE reduced NO production and ROS in all three concentrations tested. Furthermore, it was observed that EE and AE at 500 µg/mL concentration were able to reduce phagocytic activity by 30 and 50%, respectively. A scratch assay using a fibroblast cell line (NHI/3T3) showed that extracts and fractions induced cell migration with 60% wound recovery within 24 h, especially for BF. It was also observed that AF and BF had antioxidant potential in all the assays evaluated. In addition, copper chelation was observed. This activity was previously not detected in AE. The HPLC-DAD analysis showed the presence of phenolic compounds such as p-cumaric acid and vitexin for extracts, while the GNPS annotated the presence of isoorientin, vitexin, kanakugiol, and tryptamine in the BF partition phase. The data presented here demonstrated that the EE, AE, AF, and BF of C. alnifolia have potential immunomodulatory effects, antioxidant effects, as well as in vitro wound healing characteristics, which are important for dynamic inflammation process control.


Assuntos
Antioxidantes , Cicatrização , Antioxidantes/farmacologia , Estresse Oxidativo , Fenóis/farmacologia , Linhagem Celular , Extratos Vegetais/farmacologia , Extratos Vegetais/análise , Etanol/farmacologia , Folhas de Planta
5.
Molecules ; 28(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37049845

RESUMO

Oreochromis niloticus (tilapia) is one of the most cultivated fish species worldwide. Tilapia farming generates organic waste from fish removal processes in nurseries. Visceral waste can damage natural ecosystems. Therefore, the use of this material as a source of biomolecules helps reduce environmental impacts and improve pharmacological studies. Tilapia viscera were subjected to proteolysis and complexation with an ion-exchange resin. The obtained glycosaminoglycans were purified using ion exchange chromatography (DEAE-Sephacel). The electrophoretic profile and analysis of 1H/13C nuclear magnetic resonance (NMR) spectra allowed for the characterization of the compound as chondroitin sulfate and its sulfation position. This chondroitin was named CST. We tested the ability of CST to reduce leukocyte influx in acute peritonitis models induced by sodium thioglycolate and found a significant reduction in leukocyte migration to the peritoneal cavity, similar to the polymorphonuclear population of the three tested doses of CST. This study shows, for the first time, the potential of CST obtained from O. niloticus waste as an anti-inflammatory drug, thereby contributing to the expansion of the study of molecules with pharmacological functions.


Assuntos
Ciclídeos , Peritonite , Tilápia , Animais , Sulfatos de Condroitina , Ecossistema , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico
6.
Mar Drugs ; 20(8)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35892938

RESUMO

Sulfated polysaccharides (SPS) from seaweeds have great biochemical and biotechnological potential. This study aimed to investigate the effect of SPS isolated from the seaweed Caulerpa sertularioides on adipogenic differentiation as a possible alternative treatment for obesity. The SPS-rich extract from the seaweed C. sertularioides was fractioned into three SPS-rich fractions (F0.5; F0.9; and F1.8) chemically characterized. Among these four samples, only F0.9 showed a significant inhibitory effect on adipogenesis of 3T3-L1 preadipocytes. Ten SPS-rich fractions were isolated from F0.9 through ion-exchange chromatography. However, only the fraction (CS0.2) containing a sulfated glucan was able to inhibit adipogenesis. CS0.2 reduces lipid accumulation and inhibits the expression of key adipogenic (PPARγ, C/EBPß, and C/EBPα) and lipogenic markers (SREBP-1c, Fabp4, and CD36). The data points to the potential of sulfated glucan from C. sertularioides for the development of functional approaches in obesity management.


Assuntos
Caulerpa , Alga Marinha , Células 3T3-L1 , Adipócitos , Adipogenia , Animais , Caulerpa/metabolismo , Glucanos/farmacologia , Camundongos , PPAR gama/metabolismo , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia , Alga Marinha/química , Sulfatos/farmacologia
7.
Mar Drugs ; 20(8)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-36005493

RESUMO

Antioxidant compounds decrease the amount of intracellular reactive oxygen species (ROS) and, consequently, reduce the deleterious effects of ROS in osteoblasts. Here, we modified a 21 kDa fucoidan (FucA) with gallic acid (GA) using the redox method, to potentiate its antioxidant/protective capacity on pre-osteoblast-like cells (MC3T3) against oxidative stress. The 20 kDa FucA-GA contains 37 ± 3.0 mg GA per gram of FucA. FucA-GA was the most efficient antioxidant agent in terms of total antioxidant capacity (2.5 times), reducing power (five times), copper chelation (three times), and superoxide radical scavenging (2 times). Exposure of MC3T3 cells to H2O2 increased ROS levels and activated caspase-3 along with caspase-9. In addition, the cell viability decreased approximately 80%. FucA-GA also provided the most effective protection against oxidative damage caused by H2O2. Treatment with FucA-GA (1.0 mg/mL) increased cell viability (~80%) and decreased intracellular ROS (100%) and caspase activation (~80%). In addition, Fuc-GA (0.1 mg/mL) abolished H2O2-induced oxidative stress in zebra fish embryos. Overall, FucA-GA protected MC3T3 cells from oxidative stress and could represent a possible adjuvant for the treatment of bone fragility by counteracting oxidative phenomena.


Assuntos
Antioxidantes , Ácido Gálico , Animais , Antioxidantes/farmacologia , Ácido Gálico/farmacologia , Peróxido de Hidrogênio/farmacologia , Oxirredução , Estresse Oxidativo , Polissacarídeos , Espécies Reativas de Oxigênio
8.
Int J Mol Sci ; 23(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35955687

RESUMO

Leishmanolysin, also known as major promastigote protease (PSP) or gp63, is the most abundant surface glycoprotein of Leishmania spp., and has been extensively studied and recognized as the main parasite virulence factor. Characterized as a metalloprotease, gp63 can be powerfully inactivated in the presence of a metal chelator. In this study, we first used the structural parameters of a 7-hydroxycoumarin derivative, L1 compound, to evaluate the theoretical-computational experiments against gp63, comparing it with an available metal chelator already described. The methodology followed was (i) analysis of the three-dimensional structure of gp63 as well as its active site, and searching the literature and molecular databases for possible inhibitors; (ii) molecular docking simulations and investigation of the interactions in the generated protein-ligand complexes; and (iii) the individual energy of the gp63 amino acids that interacted most with the ligands of interest was quantified by ab initio calculations using Molecular Fraction with Conjugated Caps (MFCC). MFCC still allowed the final quantum balance calculations of the protein interaction to be obtained with each inhibitor candidate binder. L1 obtained the best energy quantum balance result with -2 eV, followed by DETC (-1.4 eV), doxycycline (-1.3 eV), and 4-terpineol (-0.6 eV), and showed evidence of covalent binding in the enzyme active site. In vitro experiments confirmed L1 as highly effective against L. amazonensis parasites. The compound also exhibited a low cytotoxicity profile against mammalian RAW and 3T3 cells lines, presenting a selective index of 149.19 and 380.64 µM, respectively. L1 induced promastigote forms' death by necrosis and the ultrastructural analysis revealed disruption in membrane integrity. Furthermore, leakage of the contents and destruction of the parasite were confirmed by Spectroscopy Dispersion analysis. These results together suggested L1 has a potential effect against L. amazonensis, the etiologic agent of diffuse leishmaniasis, and the only one that currently does not have a satisfactory treatment.


Assuntos
Leishmania , Animais , Quelantes , Leishmania/metabolismo , Mamíferos/metabolismo , Metaloendopeptidases/metabolismo , Metaloproteases , Camundongos , Simulação de Acoplamento Molecular , Fagocitose
9.
Mar Drugs ; 19(2)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673266

RESUMO

The global rise of infectious disease outbreaks and the progression of microbial resistance reinforce the importance of researching new biomolecules. Obtained from the hydrolysis of chitosan, chitooligosaccharides (COSs) have demonstrated several biological properties, including antimicrobial, and greater advantage over chitosan due to their higher solubility and lower viscosity. Despite the evidence of the biotechnological potential of COSs, their effects on trypanosomatids are still scarce. The objectives of this study were the enzymatic production, characterization, and in vitro evaluation of the cytotoxic, antibacterial, antifungal, and antiparasitic effects of COSs. NMR and mass spectrometry analyses indicated the presence of a mixture with 81% deacetylated COS and acetylated hexamers. COSs demonstrated no evidence of cytotoxicity upon 2 mg/mL. In addition, COSs showed interesting activity against bacteria and yeasts and a time-dependent parasitic inhibition. Scanning electron microscopy images indicated a parasite aggregation ability of COSs. Thus, the broad biological effect of COSs makes them a promising molecule for the biomedical industry.


Assuntos
Anti-Infecciosos/farmacologia , Antiparasitários/farmacologia , Quitina/análogos & derivados , Anti-Infecciosos/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antiparasitários/química , Quitina/química , Quitina/farmacocinética , Quitosana , Microscopia Eletrônica de Varredura , Oligossacarídeos , Fatores de Tempo
10.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638973

RESUMO

The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from Bacillus toyonensis. Additionally, this study aimed to structurally characterize the COS via mass spectrometry, to analyze their biocompatibility in acute toxicity models in vivo, to evaluate their healing action in a cell migration model in vitro, to analyze the anti-inflammatory activity in in vivo models of xylol-induced ear edema and zymosan-induced air pouch, and to assess the wound repair action in vivo. The structural characterization process pointed out the presence of hexamers. The in vitro and in vivo biocompatibility of COS was reaffirmed. The COS stimulated the fibroblast migration. In the in vivo inflammatory assays, COS showed an antiedematogenic response and significant reductions in leukocyte migration, cytokine release, and protein exudate. The COS healing effect in vivo was confirmed by the significant wound reduction after seven days of the experiment. These results indicated that the presence of hexamers influences the COS biological properties, which have potential uses in the pharmaceutical field due to their healing and anti-inflammatory action.


Assuntos
Anti-Inflamatórios/administração & dosagem , Materiais Biocompatíveis/administração & dosagem , Quitosana/administração & dosagem , Otopatias/tratamento farmacológico , Edema/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Cicatrização/efeitos dos fármacos , Células 3T3 , Animais , Anti-Inflamatórios/química , Bacillus/enzimologia , Materiais Biocompatíveis/química , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Citocinas/metabolismo , Modelos Animais de Doenças , Otopatias/induzido quimicamente , Edema/induzido quimicamente , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Glicosídeo Hidrolases/química , Hidrólise , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oligossacarídeos/química
11.
Molecules ; 27(1)2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-35011403

RESUMO

Animal chitosan (Chit-A) is gaining more acceptance in daily activities. It is used in a range of products from food supplements for weight loss to even raw materials for producing nanoparticles and hydrogel drug carriers; however, it has low antioxidant activity. Fungal oligochitosan (OChit-F) was identified as a potential substitute for Chit-A. Cunninghamella elegans is a fungus found in the Brazilian savanna (Caatinga) that produces OligoChit-F, which is a relatively poorly studied compound. In this study, 4 kDa OChit-F with a 76% deacetylation degree was extracted from C. elegans. OChit-F showed antioxidant activity similar to that of Chit-A in only one in vitro test (copper chelation) but exhibited higher activity than that of Chit-A in three other tests (reducing power, hydroxyl radical scavenging, and iron chelation). These results indicate that OChit-F is a better antioxidant than Chit-A. In addition, Chit-A significantly increased the formation of calcium oxalate crystals in vitro, particularly those of the monohydrate (COM) type; however, OChit-F had no effect on this process in vitro. In summary, OChit-F had higher antioxidant activity than Chit-A and did not induce the formation of CaOx crystals. Thus, OChit-F can be used as a Chit-A substitute in applications affected by oxidative stress.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Quitosana/química , Quitosana/farmacologia , Cunninghamella/metabolismo , Oligossacarídeos/biossíntese , Oligossacarídeos/farmacologia , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Oxalato de Cálcio/química , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier
12.
Mar Drugs ; 18(5)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365741

RESUMO

Sulfated polysaccharides (SPs) obtained from green seaweeds are structurally heterogeneous molecules with multifunctional bioactivities. In this work, two sulfated and pyruvated galactans were purified from Caulerpa cupressoides var. flabellata (named SP1 and SP2), and their immunostimulatory effect was evaluated using cultured murine macrophage cells. Both SPs equally increased the production of nitric oxide, reactive oxygen species, and the proinflammatory cytokines TNF-α and IL-6. NMR spectroscopy revealed that both galactans were composed primarily of 3)-ß-d-Galp-(1→3) units. Pyruvate groups were also found, forming five-membered cyclic ketals as 4,6-O-(1'carboxy)-ethylidene-ß-d-Galp residues. Some galactoses are sulfated at C-2. In addition, only SP2 showed some galactose units sulfated at C-4, indicating that sulfation at this position is not essential for the immunomodulatory activity of these galactans. Overall, the data showed that the galactans of C. cupressoides exhibited immunostimulating activity with potential therapeutic applications, which can be used in the development of new biomedical products.


Assuntos
Adjuvantes Imunológicos/metabolismo , Caulerpa/metabolismo , Galactanos/metabolismo , Macrófagos/efeitos dos fármacos , Alga Marinha , Adjuvantes Imunológicos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Galactanos/farmacologia , Macrófagos/metabolismo
13.
Molecules ; 25(9)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32354047

RESUMO

The genus Gracilaria synthesizes sulfated polysaccharides (SPs). Many of these SPs, including those synthesized by the edible seaweed Gracilaria birdiae, have not yet been adequately investigated for their use as potential pharmaceutical compounds. Previous studies have demonstrated the immunomodulatory effects of sulfated galactans from G. birdiae. In this study, a galactan (GB) was extracted from G. birdiae and evaluated by cell proliferation and antioxidant tests. GB showed no radical hydroxyl (OH) and superoxide (O2-) scavenging ability. However, GB was able to donate electrons in two further different assays and presented iron- and copper-chelating activity. Urolithiasis affects approximately 10% of the world's population and is strongly associated with calcium oxalate (CaOx) crystals. No efficient compound is currently available for the treatment of this disease. GB appeared to interact with and stabilize calcium oxalate dihydrate crystals, leading to the modification of their morphology, size, and surface charge. These crystals then acquired the same characteristics as those found in healthy individuals. In addition, GB showed no cytotoxic effect against human kidney cells (HEK-293). Taken together, our current findings highlight the potential application of GB as an antiurolithic agent.


Assuntos
Antioxidantes/química , Oxalato de Cálcio/antagonistas & inibidores , Gracilaria/química , Polissacarídeos/química , Cálcio/química , Oxalato de Cálcio/química , Sobrevivência Celular , Quelantes/farmacologia , Cobre/química , Desenho de Fármacos , Elétrons , Galactanos/química , Células HEK293 , Humanos , Hidrólise , Radical Hidroxila , Íons , Ferro/química , Rim/efeitos dos fármacos , Monossacarídeos/química , Oxigênio/química , Proteínas , Alga Marinha/química , Superóxidos/química
14.
Mar Drugs ; 17(9)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466337

RESUMO

Some antioxidant compounds decrease the amount of intracellular reactive oxygen species (ROS) and consequently reduce the deleterious effects of ROS in osteoblasts. Thus, these compounds fight against osteoporosis. Brown seaweeds are a rich source of antioxidant fucose-containing sulfated polysaccharides (fucans and fucoidans). We obtained six fucoidans (FRFs)-F0.3, F0.5, F0.7, F1.0, F1.5, and F2.1-from Dictyota mertensii by proteolytic digestion followed by sequential acetone precipitation. Except for F0.3, all FRFs showed antioxidant activity in different in vitro tests. In pre- osteoblast-like cells (MC3T3-L1) exposed to H2O2-oxidative stress, caspase-3 and caspase-9 were activated, resulting in apoptosis of the cells. We also observed a decrease in superoxide dismutase (SOD) and alkaline phosphatase (ALP) activity. The antioxidant FRFs protected the cells from the oxidative damage caused by H2O2, decreasing intracellular ROS and caspase activation, and increasing SOD activity. The most effective protection against damage was provided by F0.7, F1.5, and F2.1. At 0.5 mg/mL, these FRFs also suppressed the H2O2-mediated inhibition of ALP activity. The data indicated that FRFs F0.7, F1.5, and F2.1 from D. mertensii were antioxidants that protected bone tissue from oxidative stress and could represent possible adjuvants for the treatment of bone fragility through counteracting oxidative phenomena.


Assuntos
Sequestradores de Radicais Livres/farmacologia , Phaeophyceae/química , Polissacarídeos/farmacologia , Alga Marinha/química , Células 3T3 , Animais , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/uso terapêutico , Humanos , Peróxido de Hidrogênio/toxicidade , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Osteoporose/tratamento farmacológico , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico
15.
Mar Drugs ; 17(2)2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30744130

RESUMO

Green seaweeds are rich sources of sulfated polysaccharides (SPs) with potential biomedical and nutraceutical applications. The aim of this work was to evaluate the immunostimulatory activity of SPs from the seaweed, Caulerpa cupressoides var. flabellata on murine RAW 264.7 macrophages. SPs were evaluated for their ability to modify cell viability and to stimulate the production of inflammatory mediators, such as nitric oxide (NO), intracellular reactive oxygen species (ROS), and cytokines. Additionally, their effect on inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) gene expression was investigated. The results showed that SPs were not cytotoxic and were able to increase in the production of NO, ROS and the cytokines, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). It was also observed that treatment with SPs increased iNOS and COX-2 gene expression. Together, these results indicate that C. cupressoides var. flabellata SPs have strong immunostimulatory activity, with potential biomedical applications.


Assuntos
Adjuvantes Imunológicos/farmacologia , Caulerpa/química , Polissacarídeos/farmacologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/isolamento & purificação , Animais , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
Mar Drugs ; 17(6)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31159355

RESUMO

Urolithiasis affects approximately 10% of the world population and is strongly associated with calcium oxalate (CaOx) crystals. Currently, there is no efficient compound that can be used to prevent this disease. However, seaweeds' sulfated polysaccharides (SPs) can change the CaOx crystals surface's charge and thus modify the crystallization dynamics, due to the interaction of the negative charges of these polymers with the crystal surface during their synthesis. We observed that the SPs of Caulerpa cupressoides modified the morphology, size and surface charge of CaOx crystals. Thus, these crystals became similar to those found in healthy persons. In the presence of SPs, dihydrate CaOx crystals showed rounded or dumbbell morphology. Infrared analysis, fluorescence microscopy, flow cytometry (FITC-conjugated SPs) and atomic composition analysis (EDS) allowed us to propose the mode of action between the Caulerpa's SPs and the CaOx crystals. This study is the first step in understanding the interactions between SPs, which are promising molecules for the treatment of urolithiasis, and CaOx crystals, which are the main cause of kidney stones.


Assuntos
Antioxidantes/farmacologia , Oxalato de Cálcio/química , Caulerpa/química , Polissacarídeos/farmacologia , Humanos , Técnicas In Vitro , Cálculos Renais/química , Cálculos Renais/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Propriedades de Superfície/efeitos dos fármacos , Urolitíase/tratamento farmacológico
17.
Molecules ; 24(11)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151328

RESUMO

It has recently been shown that chitosan (Chit) induces the formation of calcium oxalate (CaOx) crystals, which are mainly responsible for the appearance of kidney stones, and this might limit the use of Chit in vivo. Here, Chit was conjugated with gallic acid (Chit-Gal) to decrease the formation of CaOx crystal. This conjugation was confirmed by FTIR and NMR analyses. Chit-Gal contains 10.2 ± 1.5 mg GA per g of Chit. Compared to the control group, Chit increased the number of crystals by six-fold, mainly in the number of monohydrated CaOx crystals, which are the most harmful CaOx crystals. In addition, Chit increased the zeta potential (ζ) of CaOx crystals by three-fold, indicating that Chit was associated with the crystals. These alterations were abolished when Chit-gal was used in these tests. As oxidative stress is related to renal calculus formation, Chit and Chit-Gal were also evaluated as antioxidants using total antioxidant Capacity (TAC), reducing power, ferrous chelation, and copper chelation tests. Chit-gal was more efficient antioxidant agent in TAC (2 times), in ferrous chelation (90 times), and in reducing Power (5 times) than Chit. Overall, Chit-gal has higher antioxidant activity than Chit, does not induce the formation of CaOx crystals. Thus, Chit-Gal has potential to be used as a chit substitute.


Assuntos
Oxalato de Cálcio/química , Quitosana/química , Ácido Gálico/química , Antioxidantes/química , Cristalização , Quelantes de Ferro/química , Cálculos Renais/química , Espectroscopia de Ressonância Magnética , Peso Molecular , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Molecules ; 24(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374887

RESUMO

Dithiocarbamates represent a class of compounds that were evaluated in different biomedical applications because of their chemical versatility. For this reason, several pharmacological activities have already been attributed to these compounds, such as antiparasitic, antiviral, antifungal activities, among others. Therefore, compounds that are based on dithiocarbamates have been evaluated in different in vivo and in vitro models as potential new antimicrobials. Thus, the purpose of this review is to present the possibilities of using dithiocarbamate compounds as potential new antitrypanosomatids-drugs, which could be used for the pharmacological control of Chagas disease, leishmaniasis, and African trypanosomiasis.


Assuntos
Antiparasitários/uso terapêutico , Leishmaniose/tratamento farmacológico , Tiocarbamatos/uso terapêutico , Trypanosoma/efeitos dos fármacos , Animais , Antiparasitários/química , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Humanos , Leishmaniose/parasitologia , Tiocarbamatos/química , Trypanosoma/patogenicidade , Tripanossomíase Africana/tratamento farmacológico , Tripanossomíase Africana/parasitologia
19.
Mar Drugs ; 16(4)2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29677120

RESUMO

Seaweed is a rich source of bioactive sulfated polysaccharides. We obtained six sulfated polysaccharide-rich fractions (UF-0.3, UF-0.5, UF-0.6, UF-0.7, UF-1.0, and UF-2.0) from the green seaweed Udotea flabellum (UF) by proteolytic digestion followed by sequential acetone precipitation. Biochemical analysis of these fractions showed that they were enriched with sulfated galactans. The viability and proliferative capacity of 3T3 fibroblasts exposed to FeSO4 (2 µM), CuSO4 (1 µM) or ascorbate (2 mM) was not affected. However, these cells were exposed to oxidative stress in the presence of FeSO4 or CuSO4 and ascorbate, which caused the activation of caspase-3 and caspase-9, resulting in apoptosis of the cells. We also observed increased lipid peroxidation, evaluated by the detection of malondialdehyde and decreased glutathione and superoxide dismutase levels. Treating the cells with the ultrafiltrate fractions (UF) fractions protected the cells from the oxidative damage caused by the two salts and ascorbate. The most effective protection against the oxidative damage caused by iron was provided by UF-0.7 (1.0 mg/mL); on treatment with UF-0.7, cell viability was 55%. In the case of copper, cell viability on treatment with UF-0.7 was ~80%, but the most effective fraction in this model was UF-2.0, with cell viability of more than 90%. The fractions, mainly UF-0.7 and UF-2.0, showed low iron chelating activity, but high copper chelating activity and total antioxidant capacity (TAC). These results suggested that some of their protective mechanisms stem from these properties.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Alga Marinha/química , Sulfatos/farmacologia , Células 3T3 , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Clorófitas/química , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Camundongos , Oxirredução/efeitos dos fármacos , Superóxido Dismutase/metabolismo
20.
Mar Drugs ; 16(6)2018 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-29867001

RESUMO

Fucus vesiculosus is a brown seaweed used in the treatment of obesity. This seaweed synthesizes various bioactive molecules, one of them being a sulfated polysaccharide known as fucoidan (FF). This polymer can easily be found commercially, and has antiadipogenic and lipolytic activity. Using differential precipitation with acetone, we obtained four fucoidan-rich fractions (F0.5/F0.9/F1.1/F2.0) from FF. These fractions contain different proportions of fucose:glucuronic acid:galactose:xylose:sulfate, and also showed different electrophoretic mobility and antioxidant activity. Using 3T3-L1 adipocytes, we found that all samples had lipolytic action, especially F2.0, which tripled the amount of glycerol in the cellular medium. Moreover, we observed that FF, F1.0, and F2.0 have antiadipogenic activity, as they inhibited the oil red staining by cells at 40%, 40%, and 50%, respectively. In addition, they decreased the expression of key proteins of adipogenic differentiation (C/EBPα, C/EBPß, and PPARγ). However, F0.5 and F0.9 stimulated the oil red staining at 80% and increased the expression of these proteins. Therefore, these fucoidan fractions have an adipogenic effect. Overall, the data show that F2.0 has great potential to be used as an agent against obesity as it displays better antioxidant, lipolytic and antiadipogenic activities than the other fucoidan fractions that we tested.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Fucus/química , Polissacarídeos/farmacologia , Células 3T3 , Animais , Antioxidantes/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Fucose/farmacologia , Galactose/farmacologia , Camundongos , PPAR gama/metabolismo , Alga Marinha/química , Sulfatos/farmacologia , Xilose/farmacologia
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