RESUMO
It was difficult for nanodrugs to simultaneously meet the contradictory requirements of prolonged circulation time, augmented cellular uptake, rapid lysosome escape, precise drug release, and tumor penetration in tumor drug delivery. We prepared a nanotransformer (DTIG) through assembling doxorubicin, tannic acid, and indocyanine green to overcome this dilemma. Hydrophilic DTIG showed prolonged blood circulation time. Besides, DTIG could be efficiently internalized by tumor cells through transforming into hydrophobic particles in an acidic tumor microenvironment. Subsequently, oversized hydrophobic particles were further formed in acidic lysosomes to escape from it through rupturing the lysosome. These hydrophobic DTIGs could rapidly revert to a smaller hydrophilic nanoassembly and release the payloads in cytoplasm. Similar to denaturation and renaturation of protein, these high-efficiency instantaneous transformations were activated by proton. Besides, photothermal therapy of DTIG promoted drug penetration efficiency in tumor. This optimized drug delivery process of DTIG finally offered potent antitumor efficacy and an obvious advantage on prognosis.
Assuntos
Doxorrubicina , Sistemas de Liberação de Medicamentos , Verde de Indocianina , Nanoestruturas , Neoplasias Experimentais , Taninos , Microambiente Tumoral/efeitos dos fármacos , Animais , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Feminino , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacocinética , Verde de Indocianina/farmacologia , Células MCF-7 , Camundongos , Camundongos Nus , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Taninos/química , Taninos/farmacocinética , Taninos/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Sanguisorba tannins are the major active ingredients in Sanguisorba ofJicinalis L. (Rosaceae), one of the most popular herbal medicines in China, is widely prescribed for hemostasis. In this study, three kinds of tannins extract from Sanguisorba officinalis L. (Rosaceae), and the metabolites in vivo and in vitro were detected and identified by high-pressure liquid chromatography, coupled with linear ion trap orbitrap tandem mass spectrometry (HPLC-LTQ-Orbitrap). For in vivo assessment, the rats were administered at a single dose of 150 mg/kg, after which 12 metabolites were found in urine, 6 metabolites were found in feces, and 8 metabolites were found in bile, while metabolites were barely found in plasma and tissues. For in vitro assessment, 100 µM Sanguisorba tannins were incubated with rat liver microsomes, liver cytosol, and feces, after which nine metabolites were found in intestinal microbiota and five metabolites were found in liver microsomes and liver cytosol. Moreover, the metabolic pathways of Sanguisorba tannins were proposed, which shed light on their mechanism.
Assuntos
Sanguisorba/química , Taninos/farmacocinética , Animais , Bile/metabolismo , Fezes/química , Microbioma Gastrointestinal , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Taninos/análise , Taninos/químicaRESUMO
Fucaceae is the most dominant algae family along the intertidal areas of the Northern Hemisphere shorelines, being part of human customs for centuries with applications as a food source either for humans or animals, in agriculture and as remedies in folk medicine. These macroalgae are endowed with several phytochemicals of great industrial interest from which phlorotannins, a class of marine-exclusive polyphenols, have gathered much attention during the last few years due to their numerous possible therapeutic properties. These compounds are very abundant in brown seaweeds such as Fucaceae and have been demonstrated to possess numerous health-promoting properties, including antioxidant effects through scavenging of reactive oxygen species (ROS) or enhancement of intracellular antioxidant defenses, antidiabetic properties through their acarbose-like activity, stimulation of adipocytes glucose uptake and protection of ß-pancreatic cells against high-glucose oxidative stress; anti-inflammatory effects through inhibition of several pro-inflammatory mediators; antitumor properties by activation of apoptosis on cancerous cells and metastasis inhibition, among others. These multiple health properties render phlorotannins great potential for application in numerous therapeutical approaches. This review addresses the major contribution of phlototannins for the biological effects that have been described for seaweeds from Fucaceae. In addition, the bioavailability of this group of phenolic compounds is discussed.
Assuntos
Fucus/química , Alga Marinha/química , Taninos/química , Taninos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Taninos/farmacocinéticaRESUMO
Geraniin (GE), an ellagitannin (ET) renowned for its promising health advantages, faces challenges in its practical applications due to its limited bioavailability. This innovative and novel formulation of GE and soy-phosphatidylcholine (GE-PL) complex has the potential to increase oral bioavailability, exhibiting high entrapment efficiency of 100.2 ± 0.8 %, and complexation efficiency of 94.6 ± 1.1 %. The small particle size (1.04 ± 0.11 µm), low polydispersity index (0.26 ± 0.02), and adequate zeta potential (-26.1 ± 0.12 mV), indicate its uniformity and stability. Moreover, the formulation also demonstrates improved lipophilicity, reduced aqueous and buffer solubilities, and better partition coefficient. It has been validated by various analytical techniques, including Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studies. Oral bioavailability and pharmacokinetics of free GE and GE-PL complex investigated in rabbits demonstrated enhanced plasma concentration of ellagic acid (EA) compared to free GE. Significantly, GE, whether in its free form or as part of the GE-PL complex, was not found in the circulatory system. However, EA levels were observed at 0.5 h after administration, displaying two distinct peaks at 2 ± 0.03 h (T1max) and 24 ± 0.06 h (T2max). These peaks corresponded to peak plasma concentrations (C1max and C2max) of 588.82 ng/mL and 711.13 ng/mL respectively, signifying substantial 11-fold and 5-fold enhancements when compared to free GE. Additionally, it showed an increased area under the curve (AUC), the elimination half-life (t1/2, el) and the elimination rate constant (Kel). The formulation of the GE-PL complex prolonged the presence of EA in the bloodstream and improved its absorption, ultimately leading to a higher oral bioavailability. In summary, the study highlights the significance of the GE-PL complex in overcoming the bioavailability limitations of GE, paving the way for enhanced therapeutic outcomes and potential applications in drug delivery and healthcare.
Assuntos
Disponibilidade Biológica , Glucosídeos , Taninos Hidrolisáveis , Animais , Coelhos , Taninos Hidrolisáveis/farmacocinética , Taninos Hidrolisáveis/química , Taninos Hidrolisáveis/administração & dosagem , Glucosídeos/farmacocinética , Glucosídeos/química , Glucosídeos/administração & dosagem , Glucosídeos/sangue , Administração Oral , Masculino , Tamanho da Partícula , Fosfatidilcolinas/química , Solubilidade , Química Farmacêutica/métodos , Ácido Elágico/farmacocinética , Ácido Elágico/química , Ácido Elágico/administração & dosagem , Ácido Elágico/sangue , Taninos/química , Taninos/farmacocinética , Taninos/administração & dosagemRESUMO
Sclerotherapy with aluminum potassium tannic acid (ALTA), which was approved in Japan for the treatment of internal hemorrhoids in July 2004 (Takano et al., Int J Colorectal Dis 21:44-51, 2006), has been widely accepted because of its effectiveness and low invasiveness. More than 200,000 patients have received ALTA injection therapy. ALTA is injected directly into 4 points of an internal hemorrhoid (4-step injection) to induce sclerosis and remission of the hemorrhoids, and consequently, resolution of symptoms such as prolapse and bleeding. The precision of the 4-step injection is considered to be a crucial determinant of the success of this therapy and the risk of complications. However, sufficient evidence has not yet been obtained concerning the diffusion and distribution of the injected drug. A pilot study visualized the real-time diffusion/distribution of the drug solution following the 4-step injection, using the ICG (indocyanine green) fluorescence technique, and an infrared camera (Photodynamic EYE; PDE, Hamamatsu Photonics K.K.).
Assuntos
Compostos de Alúmen/administração & dosagem , Compostos de Alúmen/farmacocinética , Hemorroidas/terapia , Imagem Molecular/métodos , Imagem Óptica/métodos , Escleroterapia/métodos , Taninos/administração & dosagem , Taninos/farmacocinética , Difusão , Hemorroidas/cirurgia , Humanos , Verde de Indocianina , Injeções , Imagem Óptica/instrumentação , Projetos Piloto , Soluções EsclerosantesRESUMO
In an experiment, the possible influence of tannic acid (TA) and polyethylene glycol (PEG) on the absorption capacity of intestine for d-xylose and ß-carotene in broiler chicken was investigated. Four groups of nine 28-day-old broiler cockerels received d-xylose (500 mg) and ß-carotene (52 µg) solutions (Group 1 to 4) with TA (1 g, Group 2 to 4) and PEG (500 mg Group 3 and 1 g Group 4), orally. One blood sample prior to, and four others after the administration of test materials, were collected from wing vein on 40 min basis, for 160 min and the concentration of plasma d-xylose was determined. The concentration of ß-carotene was also measured in plasma of blood samples taken prior to and 160 min post-administration of the test materials. Plasma d-xylose concentration of all groups showed quadratic correlations with time (p < 0.001, r(2) = 0.84, 0.60, 0.70 and 0.74 for Group 1 to 4, respectively). Administration of TA reduced the plasma concentration of d-xylose in Group 2. However, feeding PEG after TA raised the concentration of d-xylose in Group 4 to the level that there was no difference in that variable between this group and Group 1. Although the plasma concentration of ß-carotene was increased in 160 min post-ingestion of the test material, no difference was found in that variable among the experimental groups. In conclusion, TA and its interaction with PEG have impacts on the absorption capacity of intestine for d-xylose and highly likely other simple sugars, but TA or PEG have no influence on the absorption of ß-carotene and most probably other fat soluble vitamins.
Assuntos
Galinhas , Intestinos/efeitos dos fármacos , Polietilenoglicóis/farmacocinética , Taninos/farmacocinética , Xilose/farmacocinética , beta Caroteno/farmacocinética , Absorção , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Suplementos Nutricionais , Interações Medicamentosas , Mucosa Intestinal/metabolismo , Masculino , Polietilenoglicóis/farmacologia , Taninos/farmacologiaRESUMO
Radionuclide-functionalized drug delivery vehicles capable of being imaged via positron emission tomography (PET) are of increasing interest in the biomedical field as they can reveal the in vivo behavior of encapsulated therapeutics with high sensitivity. However, the majority of current PET-guided theranostic agents suffer from poor retention of radiometal over time, low drug loading capacities, and time-limited PET imaging capability. To overcome these challenges, we have developed hollow microcapsules with a thin (<100 nm) multilayer shell as advanced theranostic delivery systems for multiday PET tracking in vivo. The 3 µm capsules were fabricated via the aqueous multilayer assembly of a natural antioxidant, tannic acid (TA), and a poly(N-vinylpyrrolidone) (PVPON) copolymer containing monomer units functionalized with deferoxamine (DFO) to chelate the 89Zr radionuclide, which has a half-life of 3.3 days. We have found using radiochromatography that (TA/PVPON-DFO)6 capsules retained on average 17% more 89Zr than their (TA/PVPON)6 counterparts, which suggests that the covalent attachment of the DFO to PVPON provides stable 89Zr chelation. In vivo PET imaging studies performed in mice demonstrated that excellent stability and imaging contrast were still present 7 days postinjection. Animal biodistribution analyses showed that capsules primarily accumulated in the spleen, liver, and lungs with negligible accumulation in the femur, with the latter confirming the stable binding of the radiotracer to the capsule walls. The application of therapeutic ultrasound (US) (60 s of 20 kHz US at 120 W cm-2) to Zr-functionalized capsules could release the hydrophilic anticancer drug doxorubicin from the capsules in the therapeutic amounts. Polymeric capsules with the capability of extended in vivo PET-based tracking and US-induced drug release provide an advanced platform for development of precision-targeted therapeutic carriers and could aid in the development of more effective drug delivery systems.
Assuntos
Antineoplásicos/uso terapêutico , Quelantes/química , Meios de Contraste/química , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Neoplasias/tratamento farmacológico , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética , Animais , Cápsulas , Quelantes/farmacocinética , Meios de Contraste/farmacocinética , Desferroxamina/química , Desferroxamina/farmacocinética , Portadores de Fármacos/farmacocinética , Feminino , Camundongos Endogâmicos BALB C , Tomografia por Emissão de Pósitrons/métodos , Povidona/química , Povidona/farmacocinética , Medicina de Precisão/métodos , Radioisótopos/química , Taninos/química , Taninos/farmacocinética , Ondas Ultrassônicas , Zircônio/químicaRESUMO
This study reports the synthesis, characterization and biological properties of films based on poly(vinyl alcohol) (PVA) and a cationic tannin polymer derivative (TN). Films are obtained from polymeric blends by tuning the PVA/TN weight ratios. The materials are characterized through infrared spectroscopy, X-ray photoelectron spectroscopy, contact angle measurements, mechanical analyses, and scanning electron microscopy. More hydrophilic surfaces are created by modulating the PVA and TN concentrations in the blends. Disintegration tests showed that the films present durability in phosphate buffer (pH 7.4) and low stability in simulated gastric fluid (pH 1.2). The film created at 90/10 PVA/TN weight ratio and crosslinked at 109 PVA/glutaraldehyde molar ratio (sample PVA10/TN10) supports the attachment and proliferation of bone marrow mesenchymal stem cells after 7 days of culture. The scaffolding capacity of the PVA10/TN10 surface is compared with titanium, one of the most important biomedical materials used in bone replacements. Also, the PVA/TN films exhibited cytocompatibility, antioxidant and antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. These properties make PVA/TN films are candidates for biomedical applications in the tissue engineering field.
Assuntos
Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Materiais Biocompatíveis/química , Taninos/farmacocinética , Animais , Antibacterianos/química , Antioxidantes/farmacocinética , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Glutaral/química , Hidrogéis/síntese química , Hidrogéis/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Masculino , Teste de Materiais , Células-Tronco Mesenquimais/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Espectroscopia Fotoeletrônica , Álcool de Polivinil/química , Pseudomonas aeruginosa/efeitos dos fármacos , Ratos Wistar , Staphylococcus aureus/efeitos dos fármacos , Taninos/químicaRESUMO
Exendin-4 has been clinically adopted as an effective drug for treating type 2 diabetes (T2D), but its short circulation half-life in the blood requires two injections per day to maintain effective glycemic control. This significantly limits its clinical application. In this study, we developed a tannic acid/exendin-4/Fe3+ ternary nanoparticle system to provide sustained release of exendin-4 in vivo. The formation of these nanoparticles relies on TA/exendin-4 complexation and stabilization through TA-Fe3+ coordination, where the rapid reaction kinetics can benefit from efficient mixing of all three components. Adapting our recently developed flash nanocomplexation (FNC) method, we formulated nanoparticles with high encapsulation efficiency (~ 100%) of exendin-4, high payload capacity, and high degrees of uniformity and stability because the rapid turbulent mixing facilitated a homogeneous distribution of all three components in the complexation process. Intraperitoneal injection in mice showed that exendin-4 released from the nanoparticles had an AUC 7.2-fold higher than the free exendin-4 injection. Efficacy study in a T2D mouse model showed that the optimized formulation achieved a rapid reduction of the blood glucose level to the normal range within <12â¯h and maintained the same level for 72â¯h following a single intraperitoneal dose. The blood glucose level was maintained to below the therapeutic level (< 15â¯mmol/L) for 6â¯days, and the treatment led to reduced body weight with pathological and functional improvements in the kidney and liver. This tannic acid/exendin-4/Fe3+ ternary nanoparticle system holds translational potential in treating T2D, due to its improved treatment outcomes in terms of extended release of exendin-4, prolonged control of blood glucose level, reduced dosing frequency, and improved pathological indicators.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Exenatida/administração & dosagem , Hipoglicemiantes/administração & dosagem , Nanopartículas/administração & dosagem , Animais , Glicemia/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Diabetes Mellitus Experimental/sangue , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Exenatida/química , Exenatida/farmacocinética , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Ferro/administração & dosagem , Ferro/química , Ferro/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/química , Taninos/administração & dosagem , Taninos/química , Taninos/farmacocinéticaRESUMO
Oral chemotherapy has been emerging as a hopeful therapeutic regimen for the treatment of various cancers because of its high safety and convenience, lower costs, and high patient compliance. Currently, nanoparticulate drug delivery systems (NDDS) exhibit many unique advantages in mediating oral drug delivery; however, many anticancer drugs that were susceptible in hostile gastrointestinal (GI) environment showed poor permeability across intestinal epithelium, and most materials used as drug carriers are nonactive excipients and displayed no therapeutically relevant function, which leads to low oral bioavailability and therapeutic efficacy of anticancer drugs (e.g., paclitaxel). Inspired by these, in this study, paclitaxel (PTX) was used as a model drug, depending on intermolecular hydrogen-bonded interactions, PTX-loaded tannic acid/poly( N-vinylpyrrolidone) nanoparticles (PTX-NP) were produced by a flash nanoprecipitation (FNP) process. The optimized PTX-NP showed an average diameter of 54 nm with a drug encapsulation efficiency of 80% and loading capacity of 14.5%. Molecular dynamics simulations were carried out to illuminate the assembling mechanism of hydrogen-bonded PTX-NP. In vitro and in vivo results confirmed that PTX-NP showed pH-dependent intestinal site-specific drug release, P-gp inhibitory function by tannic acid (TA), prolonged intestinal retention, and improved trans-epithelial transport properties. Oral administration of PTX-NP generated a high oral delivery efficiency and relative oral bioavailability of 25.6% in rats, and further displayed a significant tumor-inhibition effect in a xenograft breast tumor model. These findings confirmed that our PTX-NP might be a promising oral drug formulation for chemotherapy.
Assuntos
Neoplasias da Mama , Portadores de Fármacos , Nanopartículas , Paclitaxel , Taninos , Administração Oral , Animais , Antineoplásicos Fitogênicos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Células CACO-2 , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Feminino , Humanos , Ligação de Hidrogênio , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , Ratos , Ratos Sprague-Dawley , Taninos/química , Taninos/farmacocinética , Taninos/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Lactoferrin (Lf) has considerable potential as a functional ingredient in food, cosmetic and pharmaceutical applications. However, the bioavailability of Lf is limited as it is susceptible to digestive enzymes in gastrointestinal tract. The shells comprising alternate layers of bovine serum albumin (BSA) and tannic acid (TA) were tested as Lf encapsulation system for oral administration. Lf absorption by freshly prepared porous 3 µm CaCO3 particles followed by Layer-by-Layer assembly of the BSA-TA shells and dissolution of the CaCO3 cores was suggested as the most efficient and harmless Lf loading method. The microcapsules showed high stability in gastric conditions and effectively protected encapsulated proteins from digestion. Protective efficiency was found to be 76 ± 6% and 85 ± 2%, for (BSA-TA)4 and (BSA-TA)8 shells, respectively. The transit of Lf along the gastrointestinal tract (GIT) of mice was followed in vivo and ex vivo using NIR luminescence. We have demonstrated that microcapsules released Lf in small intestine allowing 6.5 times higher concentration than in control group dosed with the same amount of free Lf. Significant amounts of Lf released from microcapsules were then absorbed into bloodstream and accumulated in liver. Suggested encapsulation system has a great potential for functional foods providing lactoferrin.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Lactoferrina , Soroalbumina Bovina , Taninos , Administração Oral , Animais , Cápsulas , Bovinos , Feminino , Lactoferrina/química , Lactoferrina/farmacocinética , Lactoferrina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/farmacologia , Taninos/química , Taninos/farmacocinética , Taninos/farmacologiaRESUMO
Eleven fungal strains (4 Penicillium commune, 2 Aspergillus niger, 2 Aspergillus rugulosa, Aspergillus terricola, Aspergillus ornatus and Aspergillus fumigatus) were isolated, characterized morphologically and by their capacity to degrade tannins. Aspergillus niger Aa-20 was used as control strain. Several concentrations of hydrolysable tannin (tannic acid) were used as sole carbon source. All strains were able to degrade hydrolysable tannins. Aspergillus niger GH1 and PSH showed the highest tannin-degrading capacity (67 and 70%, respectively). Also, the fungal capacity to degrade condensed tannin (catechin) was tested. Aspergillus niger PSH and Penicillium commune EH2 degraded 79.33% and 76.35% of catechin. The results demonstrated the capacity of fungi to use hydrolysable and condensed tannins as carbon source.
Assuntos
Fungos/isolamento & purificação , Plantas/microbiologia , Microbiologia do Solo , Taninos/farmacocinética , Biodegradação Ambiental , Biomassa , Catequina/farmacocinética , Clima Desértico , Fungos/crescimento & desenvolvimento , Fungos/metabolismo , MéxicoRESUMO
In this study, we monitored the inhibition and deactivation effects of various compounds associated with lignocellulosic hydrolysates on individual and combinations of cellulases. Tannic acid representing polymeric lignin residues strongly inhibited cellobiohydrolase 1 (CBH1) and ß-glucosidase 1 (BGL1), but had a moderate inhibitory effect on endoglucanase 2 (EG2). Individual monomeric lignin residues had little or no inhibitory effect on hydrolytic enzymes. However, coniferyl aldehyde and syringaldehyde substantially decreased the activity of CBH1 and deactivated BGL1. Acetic and formic acids also showed strong inhibition of BGL1 but not CBH1 and EG2, whereas tannic, acetic and formic acid strongly inhibited a combination of CBH1 and EG2 during Avicel hydrolysis. Diminishing enzymatic hydrolysis is largely a function of inhibitor concentration and the enzyme-inhibitor relationship, rather than contact time during the hydrolysis process (i.e. deactivation). This suggests that decreased rates of hydrolysis during the enzymatic depolymerisation of lignocellulosic hydrolysates may be imparted by other factors related to substrate crystallinity and accessibility.
Assuntos
Celulases/antagonistas & inibidores , Lignina/metabolismo , Lignina/farmacologia , Biomassa , Biotecnologia , Celulase/antagonistas & inibidores , Celulose/metabolismo , Celulose 1,4-beta-Celobiosidase/antagonistas & inibidores , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Glucana 1,3-beta-Glucosidase/antagonistas & inibidores , Hidrólise , Cinética , Lignina/química , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Taninos/metabolismo , Taninos/farmacocinética , beta-Glucosidase/antagonistas & inibidoresRESUMO
Practical application of tannic acid is limited because it readily binds proteins to form insoluble aggregates. In this study, tannic acid was self-assembled with fish scale gelatin hydrolysates (FSGH) to form stable colloidal complex nanoparticles. The nanoparticles prepared from 4 mg ml(-1) tannic acid and 4 mg ml(-1) FSGH had a mean particle size of 260.8 ± 3.6 nm, and showed a positive zeta potential (20.4 ± 0.4 mV). The nanoparticles acted as effective nano-biochelators and free radical scavengers because they provided a large number of adsorption sites for interaction with heavy metal ions and scavenging free radicals. The maximum adsorption capacity for Cu(2+) ions was 123.5 mg g(-1) and EC50 of DPPH radical scavenging activity was 21.6 ± 1.2 µg ml(-1). Hydroxyl radical scavenging effects of the nanoparticles were investigated by electron spin resonance spectroscopy. The copper-chelating capacity and free radical scavenging activity of the nanoparticles were associated with their capacity to inhibit Cu(2+) ion-induced barrier impairment and hyperpermeability of Caco-2 intestinal epithelial tight junction (TJ). However, α-amylase inhibitory activity of the nanoparticles was significantly lower than that of free tannic acid. The results suggest that the nanoparticles can ameliorate Cu(2+) ion induced intestinal epithelial TJ dysfunction without severely inhibiting the activity of the digestive enzymes.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Proteínas de Peixes/química , Gelatina/química , Intestinos/enzimologia , Hidrolisados de Proteína/química , Taninos/química , alfa-Amilases/metabolismo , Animais , Células CACO-2 , Cobre/metabolismo , Portadores de Fármacos/química , Peixes , Humanos , Intestinos/efeitos dos fármacos , Nanopartículas/química , Taninos/farmacocinéticaRESUMO
Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-Fe(III) nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-Fe(III) nanocoat, mimicking the sporulation and germination processes found in nature.
Assuntos
Proliferação de Células , Compostos Férricos , Protetores Solares , Taninos , Raios Ultravioleta , Animais , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Compostos Férricos/química , Compostos Férricos/farmacocinética , Compostos Férricos/farmacologia , Células HeLa , Humanos , Células Jurkat , Camundongos , Células NIH 3T3 , Protetores Solares/química , Protetores Solares/farmacocinética , Protetores Solares/farmacologia , Taninos/química , Taninos/farmacocinética , Taninos/farmacologiaRESUMO
Gammadelta T cells are innate immune cells that participate in host responses against many pathogens and cancers. Recently, phosphoantigen-based drugs, capable of expanding gammadelta T cells in vivo, entered clinical trials with the goal of enhancing innate immune system functions. Potential shortcomings of these drugs include the induction of nonresponsiveness upon repeated use and the expansion of only the Vdelta2 subset of human gammadelta T cells. Vdelta1 T cells, the major tissue subset, are unaffected by phosphoantigen agonists. Using FACS-based assays, we screened primary bovine cells for novel gammadelta T cell agonists with activities not encompassed by the current treatments in an effort to realize the full therapeutic potential of gammadelta T cells. We identified gammadelta T cell agonists derived from the condensed tannin fractions of Uncaria tomentosa (Cat's Claw) and Malus domestica (apple). Based on superior potency, the apple extract was selected for detailed analyses on human cells. The apple extract was a potent agonist for both human Vdelta1 and Vdelta2 T cells and NK cells. Additionally, the extract greatly enhanced phosphoantigen-induced gammadelta T cell expansion. Our analyses suggest that a tannin-based drug may complement the phosphoantigen-based drugs, thereby enhancing the therapeutic potential of gammadelta T cells.
Assuntos
Unha-de-Gato , Divisão Celular/efeitos dos fármacos , Frutas , Subunidade alfa de Receptor de Interleucina-2/imunologia , Malus , Extratos Vegetais/farmacologia , Receptores de Antígenos de Linfócitos T gama-delta/agonistas , Taninos/farmacocinética , Regulação para Cima/efeitos dos fármacos , Animais , Unha-de-Gato/química , Bovinos , Frutas/química , Humanos , Subunidade alfa de Receptor de Interleucina-2/biossíntese , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Malus/química , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T , Taninos/química , Taninos/uso terapêuticoRESUMO
Despite occurring in a wide variety of taxa, deliberate soil consumption (geophagy) is a poorly understood behavior. In humans, geophagy is sometimes considered aberrant or a sign of metabolic dysfunction. However, geophagy is normally assigned an adaptive function in nonhuman primates and various other organisms. One hypothesis submits that clay-rich soil adsorbs intestinal insults, namely plant metabolites or diarrhoea-causing enterotoxins. Here we test the capacity of kaolin, a commonly ingested clay, to adsorb quinine (an alkaloid) and two types of tannin (digestion-inhibitors). Trials were conducted in vitro using the TNO Intestinal Model, a device that closely simulates digestion by the human stomach and small intestine. Kaolin reduced the bioavailability of each compound by < or =30%. However, because we could not replicate clay-epithelial adhesion and reduced motility, these results may underestimate adsorption in vivo. We also show that kaolin fails to render calcium oxalate soluble. We conclude that gastrointestinal adsorption is the most plausible function of human geophagy. Adaptive advantages include greater exploitation of marginal plant foods and reduced energetic costs of diarrhoea, factors that could account for the high frequency of geophagy in children and pregnant women across the tropics.
Assuntos
Adaptação Fisiológica/fisiologia , Comportamento Alimentar/fisiologia , Intestino Delgado/fisiologia , Caulim/química , Modelos Anatômicos , Solo , Adsorção , Disponibilidade Biológica , Humanos , Quinina/química , Quinina/farmacocinética , Taninos/química , Taninos/farmacocinéticaRESUMO
The degree of obturation of dentinal tubules as well as the dentinal uptake of F, Zn and Sr was investigated after placement of glass ionomer cement (GIC) containing variable proportions of the tannin-fluoride preparation, HY agent, into freshly prepared cavities. It was found that when HY agent was incorporated into the cement powder, there was both increase in electrical resistance in the dentinal floor of the GIC-restored cavity in addition to inhibition of dye penetration. Further, these changes were directly proportional to the concentration of HY agent. Electron probe microanalysis of the principal constituents of HY agent (F, Zn and Sr) revealed that the penetration depth for F and Zn was also directly proportional to the relative amount of incorporated HY agent, whereas Sr could not be detected regardless of HY concentration. Results clearly demonstrated that the higher the concentration of HY agent incorporated into GIC, the greater the degree of dentinal tubular obturation.
Assuntos
Permeabilidade da Dentina/efeitos dos fármacos , Cimentos de Ionômeros de Vidro/farmacologia , Animais , Bovinos , Dentina/efeitos dos fármacos , Dentina/metabolismo , Dentina/ultraestrutura , Relação Dose-Resposta a Droga , Microanálise por Sonda Eletrônica , Fluoretos/farmacocinética , Cimentos de Ionômeros de Vidro/química , Cimentos de Ionômeros de Vidro/farmacocinética , Estrôncio/farmacocinética , Taninos/farmacocinética , Zinco/farmacocinéticaRESUMO
The protective effects of various tannins on ocular lens against the induced oxidative damage were examined. Oxidative damage on mouse lenses was induced by incubating them with xanthine-xanthine oxidase, ADP and Fe3+ (X.XOD system). X.XOD system caused an increase in lipid peroxide of lens membrane and decreases in Na,K-ATPase and GSH reductase activities in the lenses. After pretreatment of lenses with X.XOD system, the lenses were incubated with tannins in the medium containing no X.XOD system and the effects of tannins on biochemical parameters in the lenses were determined. Higher molecular tannins (penta-O-galloyl-beta-D-glucopyranose and geraniin) decreased the lipid peroxide in the lens and restored GSH content, Na,K-ATPase and GSH reductase activities in the lens to the level comparable to control. However, all of tannins tested restored much insufficiently the cation level (ratio of Na+/K+) in the lens regardless of extents of restoration of Na,K-ATPase level by them. Because it was supposed that tannins might act primarily on the plasma membrane, the effect of tannins on lens plasma membrane was examined using cell free system. Lens was homogenated and separated into membrane pellet and supernatant. When the pellet was treated with X.XOD system, the lipid peroxide in the pellet increased and its Na,K-ATPase activity decreased. In addition, the treated pellet decreased the GSH level and GSH reductase activity in the supernatant, when the pellet was combined with the supernatant. Higher molecular tannins reduced lipid peroxide content in the X.XOD-treated pellet to control level and the pellet in which lipid peroxide content was reduced by tannins caused much less decreases of GSH level and GSH reductase activity in the supernatant. These results suggest that, in intact lens, higher molecular tannins act on plasma membrane to eliminate lipid peroxide produced by the X.XOD system and consequently suppress the decreases in both Na,K-ATPase and GSH reductase activities without their entering inside the cell.
Assuntos
Cristalino/metabolismo , Taninos/farmacologia , Xantina Oxidase/farmacologia , Xantinas/farmacologia , Animais , Sistema Livre de Células/efeitos dos fármacos , Glutationa Redutase/metabolismo , Técnicas In Vitro , Cristalino/enzimologia , Cristalino/patologia , Peróxidos Lipídicos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Oxirredução , ATPase Trocadora de Sódio-Potássio/metabolismo , Taninos/farmacocinética , XantinaRESUMO
BACKGROUND & AIMS: Punicalagin is an antioxidant ellagitannin of pomegranate juice. This compound is responsible for the high antioxidant activity of this juice. Nothing is known about the bioavailability and metabolism of punicalagin or other food ellagitannins. The present work aims to evaluate the bioavailability and metabolism of punicalagin in the rat as an animal model. DESIGN: Two groups of rats were studied. One fed with standard rat diet (n = 5) and another with the same diet plus 6 % punicalagin (n = 5). Samples of urine and faeces were taken during 37 days and plasma every week. The different metabolites were analysed by HPLC-MS-MS. RESULTS: The daily intake of punicalagin ranged from 0.6 to 1.2 g. Values around 3-6 % the ingested punicalagin were excreted as identified metabolites in faeces and urine. In faeces, punicalagin is transformed to hydrolysis products and partly metabolites by the rat microflora to 6H-dibenzo[b,d]pyran-6-one derivatives. In plasma, punicalagin was detected at concentrations around 30 microg/mL, and glucuronides of methyl ether derivatives of ellagic acid were also detected. 6H-Dibenzo[b,d]pyran-6-one derivatives were also detected especially during the last few weeks of the experiment. In urine, the main metabolites observed were the 6H-dibenzo[b,d]pyran-6-one derivatives, as aglycones or glucuronides. CONCLUSION: As only 3-6 % of the ingested punicalagin was detected as such or as metabolites in urine and faeces, the majority of this ellagitannin has to be converted to undetectable metabolites (i. e. CO(2)) or accumulated in non-analysed tissues, however with only traces of punicalagin metabolites being detected in liver or kidney. This is the first report on the absorption of an ellagitannin and its presence in plasma. In addition, the transformation of ellagic acid derivatives to 6H-dibenzo[b,d]pyran-6-one derivatives in the rat is also confirmed.