ABSTRACT
The bioaccessibility of tannins as antioxidants in meat is essential to maximise their effectiveness in protecting the product. This property determines the amount of tannins available to interact with meat components, inhibiting lipid and protein oxidation and, consequently, prolonging shelf life and preserving the sensory quality of the product. The objective of this study was to evaluate the bioaccessibility of condensed tannins (CT) from Acacia mearnsii extract (AME) and their effect on the physico-chemical characteristics of fattened lamb meat. Thirty-six Dorset × Hampshire lambs (3 months old and 20.8 ± 3.3 kg live weight) were used. The lambs were distributed equally (n = 9) into four treatments: T1, T2, T3 and T4, which included a basal diet plus 0%, 0.25%, 0.5% and 0.75% of CT from AME, respectively. At the end of the fattening period, bioaccessibility was evaluated, the animals were slaughtered and a sample of the longissimus dorsi (LD) muscle was collected to assess colour, lipid oxidation, cooking weight loss and shear force on days 1, 4, 7 and 14 of shelf-life, in samples preserved at -20 °C. In addition, the long chain fatty acid profile was analysed. A completely randomised design was used, and the means were compared with Tukey's test (P < 0.05). The mean lightness (L*), yellowness (b*) and hue (H*) values were higher for T3 and T4. The addition of CT did not affect (P > 0.05) redness (a*), cooking weight loss (CWL) or shear force (SF). T4 decreased (P < 0.05) stearic acid and increased cis-9 trans-12 conjugated linoleic acid (CLA). Bioaccessibility was higher in the supplemented groups (T1 < T2, T3 and T4). In conclusion, supplementing CT from AME in the diet of lambs did not reduce lipid oxidation, but T3 or T4 improved some aspects of meat colour and CLA deposition.
Subject(s)
Proanthocyanidins , Animals , Sheep , Proanthocyanidins/pharmacokinetics , Antioxidants/pharmacokinetics , Biological Availability , Red Meat/analysis , Meat/analysis , Cooking , Plant Extracts/chemistry , Muscle, Skeletal/metabolism , Muscle, Skeletal/chemistryABSTRACT
Whey proteins and oligomeric proanthocyanidins have nutritional value and are widely used in combination as food supplements. However, the effect of the interactions between proanthocyanidins and whey proteins on their stability has not been studied in depth. In this work, we aimed to characterize the interactions between ß-Lactoglobulin (ß-LG) and α-lactalbumin (α-LA) and oligomeric proanthocyanidins, including A1, A2, B1, B2, B3, and C1, using multi-spectroscopic and molecular docking methods. Fluorescence spectroscopic data revealed that all of the oligomeric proanthocyanidins quenched the intrinsic fluorescence of ß-LG or α-LA by binding-related fluorescence quenching. Among the six oligomeric proanthocyanidins, A1 showed the strongest affinity for ß-LG (Ka = 2.951 (±0.447) × 104 Lâmol-1) and α-LA (Ka = 1.472 (±0.236) × 105 Lâmol-1) at 297 K. ß-LG/α-LA and proanthocyanidins can spontaneously form complexes, which are mainly induced by hydrophobic interactions, hydrogen bonds, and van der Waals forces. Fourier-transform infrared spectroscopy (FTIR) and circular dichroism spectroscopy showed that the secondary structures of the proteins were rearranged after binding to oligomeric proanthocyanidins. During in vitro gastrointestinal digestion, the recovery rate of A1 and A2 increased with the addition of WPI by 11.90% and 38.43%, respectively. The addition of WPI (molar ratio of 1:1) increased the retention rate of proanthocyanidins A1, A2, B1, B2, B3, and C1 during storage at room temperature by 14.01%, 23.14%, 30.09%, 62.67%, 47.92%, and 60.56%, respectively. These results are helpful for the promotion of protein-proanthocyanidin complexes as functional food ingredients in the food industry.
Subject(s)
Proanthocyanidins/chemistry , Whey Proteins/chemistry , Circular Dichroism , Digestion , Food Storage , Lactalbumin/chemistry , Lactoglobulins/chemistry , Molecular Docking Simulation , Proanthocyanidins/metabolism , Proanthocyanidins/pharmacokinetics , Spectrometry, Fluorescence , Spectroscopy, Fourier Transform Infrared , Temperature , Thermodynamics , Whey Proteins/metabolismABSTRACT
W/O/W emulsions were easily prepared by oleogelation of the oil phase using rice bran wax (RBX) and their microstructure, stability, rheology and protection of proanthocyanidins and ß-carotene were investigated. Formation of the W/O/W emulsion was confirmed using confocal laser scanning microscopy and staining of the inner aqueous phase by tartrazine. The average particle size and viscosity of the emulsion increased as the RBX concentration increased. Moreover, RBX increased the stability of the emulsion and the emulsion was the most stable when the RBX concentration was 8.0% or 10.0%. On the other hand, the W/O/W emulsions were used to simultaneously encapsulate proanthocyanidins and ß-carotene. Specifically, proanthocyanidins and ß-carotene in RBX-containing emulsions were more stable and had higher bioaccessibility than in the emulsion without RBX. Besides, both their chemical stability and bioaccessibility reached the maximum value when the RBX concentration was 8.0% or 10.0%. In summary, the optimal RBX concentration was 8.0%.
Subject(s)
Emulsions/chemistry , Proanthocyanidins/chemistry , Rice Bran Oil/chemistry , beta Carotene/chemistry , Corn Oil/chemistry , Food Storage , Particle Size , Proanthocyanidins/pharmacokinetics , Rheology , Viscosity , Water/chemistry , beta Carotene/pharmacokineticsABSTRACT
Proanthocyanidins (PAs) are a group of polyphenols enriched in plant and human food. In recent decades, epidemiological studies have upheld the direct relationship between PA consumption and health benefits; therefore, studies on PAs have become a research hotspot. Although the oral bioavailability of PAs is quite low, pharmacokinetics data revealed that some small molecules and colonic microbial metabolites of PAs could be absorbed and exert their health beneficial effects. The pharmacological effects of PAs mainly include anti-oxidant, anticancer, anti-inflammation, antimicrobial, cardiovascular protection, neuroprotection, and metabolism-regulation behaviors. Moreover, current toxicological studies show that PAs have no observable toxicity to humans. This review summarizes the resources, extraction, structures, pharmacokinetics, pharmacology, and toxicology of PAs and discusses the limitations of current studies. Areas for further research are also proposed.
Subject(s)
Proanthocyanidins/chemistry , Proanthocyanidins/pharmacokinetics , Animals , Anti-Infective Agents , Anti-Inflammatory Agents , Antineoplastic Agents, Phytogenic , Antioxidants , Gastrointestinal Microbiome/physiology , Humans , Neuroprotective Agents , Polymers , Proanthocyanidins/isolation & purification , Proanthocyanidins/toxicityABSTRACT
This study assessed the phenolics and their bioaccessibility through an in vitro digestion system coupled to a simulated intestinal barrier in eight edible flowers of distinct colors, namely mini rose, torenia, mini daisy, clitoria, cosmos, cravine, begonia and tagete. The antioxidant activity of the flowers before in vitro digestion, in their derived dialyzed and non-dialyzed fractions was evaluated using distinct approaches. All flowers presented in their composition phenolic acids, stilbenes, flavanol, anthocyanin, flavonol and flavanone, however distinct compounds and contents were found in each flower. The bioaccessibility varied among the phenolics and within the flower source (p < 0.05). Cosmos presented the highest (p < 0.05) content of phenolics and activity in ORAC assay before in vitro digestion and in dialyzed and non-dialyzed fraction; the observed activity was correlated (r = 0.9) to its major compounds, hesperidin and rutin, as well as to caftaric acid and procyanidin B2. Mini rose displayed the highest antioxidant activity in FRAP and DPPH assays before in vitro digestion; its dialyzed and non-dialyzed fraction showed the highest activity in FRAP, correlated to pelargonidin 3,5-diglucoside, catechin, epicatechin galate, epicagocatechin galate, procyanidin A2, quercitin 3-glucoside and trans-resveratrol (r = 0.9). In DPPH assay, mini rose showed the highest activity in the non-dialyzed fraction, while cravine showed the highest activity in the dialyzed fraction, which was mainly correlated to syringic acid (r = 1.0), pelargonidin 3,5-diglucoside and epicatechin (r = 0.9). Results show great variability in the phenolic composition and their bioaccessibility among the edible flowers studied. Our findings indicate cosmos and mini rose as sources of bioaccessible phenolics with great antioxidant activity.
Subject(s)
Antioxidants/pharmacokinetics , Flowers/chemistry , Polyphenols/pharmacokinetics , Anthocyanins/analysis , Anthocyanins/pharmacokinetics , Antioxidants/analysis , Biflavonoids/analysis , Biflavonoids/pharmacokinetics , Catechin/analogs & derivatives , Catechin/analysis , Catechin/pharmacokinetics , Digestion , Gallic Acid/analogs & derivatives , Gallic Acid/analysis , Gallic Acid/pharmacokinetics , Hydroxybenzoates/analysis , Hydroxybenzoates/pharmacokinetics , Phenols/analysis , Phenols/pharmacokinetics , Polyphenols/analysis , Principal Component Analysis , Proanthocyanidins/analysis , Proanthocyanidins/pharmacokinetics , Rosa/chemistry , Rosa/classification , Rutin/analysis , Rutin/pharmacokinetics , Stilbenes/analysis , Stilbenes/pharmacokineticsABSTRACT
SCOPE: The majority of ingested flavanols reach the colon where they are catabolized by the microbiota to form hydroxyphenyl-γ-valerolactones (HGVLs). It is not known if the HGVLs are catabolic products of monomeric (epi)catechins (EPC), oligomeric procyanidins (OPCs), or both. Using data from a randomized, double-blind, placebo-controlled crossover trial the relative contributions of catechins and OPC to the bioavailable pool of HGVLs are estimated. METHODS AND RESULTS: Participants ingested an apple extract once daily for 28 days that delivered the following: i) 70 mg EPC and 65 mg OPC (low dose EPC), ii) 140 mg EPC and 130 mg OPC (high dose EPC), iii) 6 mg EPC and 130 mg OPC (OPC), and iv) a placebo control. Urine is collected over a 24-h period before and after treatments. The median urinary excretion of HGVLs after ingestion of the high dose EPC is tenfold higher than that excreted after ingestion of the OPC that provided an equivalent dose of PC. Approximately 22% of catechins are converted to HGVLs in contrast to PC, for which there is limited conversion. CONCLUSION: Monomeric catechins are efficiently converted to derived HGVLs that are absorbed and excreted in human urine, whereas oligomeric PCs are much less efficiently converted.
Subject(s)
Catechin/pharmacokinetics , Gastrointestinal Microbiome/physiology , Lactones/metabolism , Proanthocyanidins/pharmacokinetics , Aged , Biological Availability , Blood Pressure/drug effects , Catechin/chemistry , Catechin/urine , Female , Gastrointestinal Microbiome/drug effects , Humans , Lactones/chemistry , Lactones/urine , Male , Malus/chemistry , Middle Aged , Observer Variation , Placebos , Plant Extracts/chemistry , Proanthocyanidins/chemistryABSTRACT
In this paper, the Dynamic Gastrointestinal Simulator (simgi®) is used as a model to the study the metabolic activity of probiotics at the intestinal level, and in particular, to assess the impact of probiotic supplementation in the microbial metabolism of grape polyphenols. Two independent simulations using fecal samples from two healthy volunteers were carried out. Changes in microbiota composition and in metabolic activity were assessed by qPCR and 16S rRNA gene sequencing and by analyses of phenolic metabolites and ammonium ions (NH4+). The strain Lactobacillus plantarum CLC 17 was successfully implanted in the colon compartments of the simgi® after daily feeding of 2 × 1010 CFU/day for 7 days. Overall, no changes in bacterial diversity were observed after probiotic implantation. In comparison to the digestion of the grape polyphenols on their own, the inclusion of L. plantarum CLC 17 in the simgi® colon compartments led to a greater formation of phenolic metabolites such as benzoic acids, probably by the breakdown of high-molecular-weight procyanidin polymers. These results provide evidence that the probiotic strain Lactobacillus plantarum CLC 17 may improve the metabolism of dietary polyphenols when used as a food ingredient.
Subject(s)
Gastrointestinal Microbiome , Gastrointestinal Tract/microbiology , Polyphenols/pharmacokinetics , Probiotics , Vitis/chemistry , Adult , Ammonium Compounds/metabolism , Benzoates/metabolism , Biflavonoids/analysis , Biflavonoids/pharmacokinetics , Catechin/analysis , Catechin/pharmacokinetics , Colony Count, Microbial , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Diet, Western , Female , Gastrointestinal Tract/metabolism , Healthy Volunteers , Humans , Lactobacillus plantarum/metabolism , Molecular Weight , Polyphenols/analysis , Proanthocyanidins/analysis , Proanthocyanidins/pharmacokinetics , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/isolation & purification , Sequence Analysis, DNAABSTRACT
Studying bioavailability of polyphenols is essential to understand the health effects of these compounds. Human epithelial cells are commonly used in intestinal absorption and transport experiments but the changes polyphenols undergo during incubation, due to their chemical instability under the cell culture conditions, are scarcely known and might lead to inaccurate conclusions. Based on abundance of flavanols and hydroxycinnamic acids in the diet, epicatechin, epicatechin-3-gallate and procyanidin B2 as flavanols along with 5-caffeoylquinic and 3,5-dicaffeoylquinic acids as hydroxycinnamic acids were selected to comparatively evaluate their absorption and metabolism using an in vitro Caco-2 cell model. Special emphasis was paid to the structure-stability relationship of these phenolic compounds in Dulbecco's Modified Eagle's Medium (DMEM) under the cell culture conditions. The tested compounds were scarcely absorbed and minimally metabolized by the intestinal epithelium cells. The cell transport study showed prevalent efflux for flavanols opposite to absorption for hydroxycinnamates. Intestinal metabolism revealed that hydroxycinnamates were preferentially hydrolyzed and subsequently methylated, whereas hydrolysis of flavanols could not be confirmed, being mostly conjugated to sulfate, methyl- and methyl-sulfate derivatives. It is noteworthy that methyl derivatives of procyanidin-B2 were detected inside Caco-2 cells, confirming its absorption. In addition, culture medium influenced phenol isomerization to a higher extent than cells. In conclusion, hydroxycinnamates were better absorbed than flavanols although their bioavailability was limited in this intestinal cell model.
Subject(s)
Coumaric Acids/analysis , Coumaric Acids/pharmacokinetics , Polyphenols/analysis , Polyphenols/pharmacokinetics , Biflavonoids/analysis , Biflavonoids/pharmacokinetics , Biological Availability , Biological Transport , Caco-2 Cells , Catechin/analogs & derivatives , Catechin/analysis , Catechin/pharmacokinetics , Culture Media/chemistry , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Evaluation Studies as Topic , Humans , Hydrolysis , Intestinal Absorption/drug effects , Intestinal Mucosa/cytology , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Proanthocyanidins/analysis , Proanthocyanidins/pharmacokineticsABSTRACT
The ultimate health benefits of peanuts and tree nuts partially depend on the effective gastrointestinal delivery of their phytochemicals. The chemical composition and in vitro bioaccessibility of tocopherols, tocotrienols and phenolic compounds from peanuts and seven tree nuts were evaluated by analytical and chemometric methods. Total fat and dietary fiber (g 100 g-1) ranged from 34.2 (Emory oak acorn) to 72.5 (pink pine nut; PPN) and from 1.2 (PPN) to 22.5 (pistachio). Samples were rich in oleic and linoleic acids (56-87 g 100 g-1 oil). Tocopherols and tocotrienols (mg·kg-1) ranged from 48.1 (peanut) to 156.3 (almond) and 0 (almond, pecan) to 22.1 (PPN) and hydrophilic phenolics from 533 (PPN) to 12,896 (Emory oak acorn); flavonoids and condensed tannins (mg CE.100 g-1) ranged from 142 (white pine nut) to 1833 (Emory oak acorn) and 14 (PPN) to 460 (Emory oak acorn). Three principal components explained 90% of the variance associated with the diversity of antioxidant phytochemicals in samples. In vitro bioaccessibility of tocopherols, tocotrienols, hydrophilic phenolics, flavonoids, and condensed tannins ranged from 11-51%, 16-79%, 25-55%, 0-100%, and 0-94%, respectively. Multiple regression analyses revealed a potential influence of dietary fiber, fats and/or unsaturated fatty acids on phytochemical bioaccessibility, in a structure-specific manner.
Subject(s)
Antioxidants/pharmacokinetics , Nuts/chemistry , Phytochemicals/pharmacokinetics , Biological Availability , Flavonoids/pharmacokinetics , Humans , Hydroxybenzoates/pharmacokinetics , Principal Component Analysis , Proanthocyanidins/pharmacokinetics , Regression Analysis , Tocopherols/pharmacokinetics , Tocotrienols/pharmacokineticsABSTRACT
The low solubility, instability, and low bioavailability of food bioactive compounds such as polyphenols and flavonoids, restrict their applications in the fields of food science and nutrition. Ferritin protein has received more and more attention in encapsulation and delivery of the bioactive compounds due to its nanosized shell-like structure and its reversible self-assembly character. After encapsulation, bioactive compounds can be functionalized by the ferritin vehicle to achieve stabilization, solubilization, and targeted delivery. In addition, the outer interfaces and the porous structure of ferritin are also artfully harnessed for encapsulation. This review focuses on the newest advances in the fabrication, characterization, and application of ferritin-based nano-carriers for bioactive compounds by the reversible self-assembly, outer-interface decoration methods, and the channel-directed approach. The functional improvements of food bioactive compounds, including their solubility, stability, and cellular uptake, are emphasized. The limitations that affect ferritin encapsulation are also examined.
Subject(s)
Ferritins/chemistry , Ferritins/pharmacokinetics , Food , Nanostructures/chemistry , Anthocyanins/administration & dosage , Anthocyanins/chemistry , Anthocyanins/pharmacokinetics , Biological Availability , Catechin/analogs & derivatives , Catechin/chemistry , Chitosan/chemistry , Curcumin/administration & dosage , Curcumin/chemistry , Curcumin/pharmacokinetics , Humans , Polyphenols/administration & dosage , Polyphenols/chemistry , Polyphenols/pharmacokinetics , Proanthocyanidins/administration & dosage , Proanthocyanidins/chemistry , Proanthocyanidins/pharmacokinetics , Solubility , beta Carotene/administration & dosage , beta Carotene/chemistry , beta Carotene/pharmacokineticsABSTRACT
The health-promoting functions of fruit phenolic compounds are mainly attributed to their metabolites. The organic cultivation of fruits is becoming increasingly popular. Thus, this study evaluates whether the differences in red Grenache grapes derived from organic culture conditions influence the bioavailability and metabolism of phenolic compounds in rats. Organic and nonorganic (conventional) red Grenache grapes (OG and CG, respectively) were characterized and administered to Wistar rats (65â¯mg gallic acid equivalents/kg bw). Serum was recollected at different time points, and the phenolic metabolites were quantified by HPLC-ESI-MS/MS. The results showed that organic cultivation increased the oligomeric proanthocyanidin and anthocyanidin contents and decreased the content of free flavanols and dietary fiber. The serum profile of OG-administered rats showed higher metabolite concentrations at 2â¯h and reduced metabolite concentration at 24â¯h compared with the CG-administered rats. Thus, this particular serum kinetic behavior might influence the bioactivity of their phenolic compounds.
Subject(s)
Organic Agriculture , Phenols/pharmacokinetics , Vitis/chemistry , Animals , Anthocyanins/analysis , Anthocyanins/pharmacokinetics , Biological Availability , Chromatography, High Pressure Liquid , Dietary Fiber/analysis , Food Analysis/methods , Fruit/chemistry , Male , Phenols/analysis , Polyphenols/analysis , Polyphenols/pharmacokinetics , Proanthocyanidins/analysis , Proanthocyanidins/pharmacokinetics , Rats, Wistar , Tandem Mass SpectrometryABSTRACT
Reducing starch digestibility can significantly benefit efforts to combat obesity and associated chronic diseases. Polymeric proanthocyanidins (PA) form complexes with starch via unknown mechanisms, resulting in dramatically decreased starch digestibility. We hypothesized that V-type complexes are involved in these interactions. Sorghum derived PA was complexed with amylose, amylopectin, and granular maize starches in regular and deuterated solvents, and structural properties and in vitro digestibility of the complexes investigated. Based on iodine binding, X-ray diffraction patterns, crystallinity, and thermal properties, we demonstrated, for the first time, that type II semi-crystalline V-complexes are formed between amylose and PA. Furthermore, suppression of H-bonding led to amorphous complexes, suggesting extensive H-bonding facilitate and/or stabilize the V-complexes. We speculate that the complexation involves inclusion of B-rings of the PA units into the amylose helical cavity. The V-complex formation significantly increased resistant starch in gelatinized normal starch and pure amylose (by 35-45%), indicating likely physiological benefits.
Subject(s)
Amylose/chemistry , Proanthocyanidins/chemistry , Starch/chemistry , Amylopectin/chemistry , Amylose/pharmacokinetics , Digestion , Humans , Hydrogen Bonding , Iodine/metabolism , Proanthocyanidins/pharmacokinetics , Sorghum/chemistry , Starch/pharmacokinetics , X-Ray Diffraction , Zea mays/chemistryABSTRACT
Small unilamellar and multilayered liposomes loaded with polymeric (epi)catechins up to pentamers were produced. The bioaccessibility, kinetic release profile, and degradation under in vitro gastrointestinal conditions were monitored by UHPLC-DAD-QTOF-MS/MS. The results show that all of the procyanidins underwent depolymerization and epimerization into small molecular oligomers and mainly to (epi)catechin subunits. Moreover, all of the liposome formulations presented higher bioaccessibility and antioxidant activity in comparison to their respective counterparts in non-encapsulated form. Similar results were obtained with procyanidins from cocoa extract-loaded liposomes. Namely, the bioaccessibility of dimer, trimer, and tetramer fractions from cocoa-loaded liposomes were 4.5-, 2.1-, and 9.3-fold higher than those from the non-encapsulated cocoa extract. Overall, the procyanidin release profile was dependent on their chemical structure and physicochemical interaction with the lipid carrier. These results confirmed that liposomes are efficient carriers to stabilize and transport procyanidins with the aim of enhancing their bioaccessibility at a controlled release rate.
Subject(s)
Antioxidants/metabolism , Liposomes , Proanthocyanidins/metabolism , Proanthocyanidins/pharmacokinetics , Biological Availability , Calcium-Binding Proteins/chemistry , Catechin/metabolism , Chemical Phenomena , Digestion , Drug Stability , Kinetics , Liposomes/chemistry , Liposomes/metabolism , Microscopy, Electron, Transmission , Molecular Structure , Pancreatin/metabolism , Pepsin A/metabolism , Proanthocyanidins/chemistry , Transcription FactorsABSTRACT
The bioaccessibility of phenolics and antioxidant activity were determined in açaí, cupuaçu, blackberry, blueberry, jabuticaba, raspberry, cajá and soursop frozen pulps (FPs) using a digestion model coupled with a simulated intestinal barrier. Cyanidin 3-glucoside (6.56%) and pelargonidin 3-glucoside (28.33%) were bioaccessible in blueberry and raspberry. Catechin had the highest bioaccessibility in blueberry (270.71%), blackberry (137.51%), and jabuticaba (99.52%), while the highest bioaccessibility of epicatechin (153.59%) and syringic acid (147.14%) was observed in blueberry. Procyanidin B1 presented the highest bioaccessibility in cajá (102.79%) and blackberry (87.62%) and contributed to the high DPPH⪠scavenging activity observed in these FPs. The bioaccessible fraction in soursop consisted of caffeic (8.18%), p-coumaric (7.36%), caftaric (7.96%) and chlorogenic (11.08%) acids, and these acids were correlated with the iron reduction capacity of this FP. Our study assessed the bioaccessible phenolics in several FPs and showed that those found in cajá and blackberry possesses the highest antioxidant activity.
Subject(s)
Antioxidants/pharmacology , Fruit/chemistry , Phenols/pharmacokinetics , Anacardiaceae/chemistry , Anthocyanins/pharmacokinetics , Antioxidants/analysis , Biflavonoids/pharmacokinetics , Blueberry Plants/chemistry , Brazil , Catechin/pharmacokinetics , Digestion , Freezing , Glucosides/pharmacokinetics , Phenols/analysis , Proanthocyanidins/pharmacokinetics , Rubus/chemistryABSTRACT
This study investigated the possible enhancement of berberine's (BB) hypoglycemic activity by oligomeric proanthocyanidins (OPCs) and its underlying mechanism. The hypoglycemic activity of the studied compounds was evaluated in diabetic db/db mice. The cellular uptake and efflux of BB with or without OPCs were investigated using Caco-2 intestinal cells. A pharmacokinetic study of BB and OPCs was performed in Sprague Dawley (SD) mice by oral administration of the study compounds. Liquid chromatographyâ»tandem mass spectrometry (LCâ»MS/MS) was employed to determine the cellular efflux, retention, and the serum concentrations of the compounds. The results revealed that OPCs considerably potentiated the hypoglycemic efficacy of BB in diabetic db/db mice. In the in vitro experiments, OPCs significantly inhibited the efflux and increased the uptake of the P-glycoprotein (P-gp) substrate rhodamine-123 (R123) and BB in Caco-2 intestinal cells. Moreover, OPCs substantially reduced the expression of P-gp in Caco-2 cells. The inhibition of BB efflux by OPCs was translated into the improved pharmacokinetics in vivo. When co-administered, OPCs obviously increased the average maximum concentration of BB in mice. In summary, this study demonstrated that combination of BB with OPCs could significantly improve the pharmacokinetics and hypoglycemic efficacy of BB, which is valuable for future exploration of the combination of BB and OPCs as oral hypoglycemic agents.
Subject(s)
Berberine/metabolism , Berberine/pharmacokinetics , Hypoglycemic Agents/pharmacokinetics , Proanthocyanidins/pharmacokinetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/pharmacology , Animals , Biological Transport/drug effects , Caco-2 Cells , Chromatography, Liquid , Humans , Male , Mice , Mice, Inbred C57BL , Proanthocyanidins/chemistry , Proanthocyanidins/pharmacology , Rhodamines , Tandem Mass SpectrometryABSTRACT
The stability and bioaccessibility of polyphenol from Acacia mearnsii bark were measured at various stages during in vitro simulated digestion. Subsequently, the changes in the total polyphenol content (TPC) and biological activity were studied. The results showed that the phenolic compounds from A. mearnsii remained stable, and TPC underwent few changes during gastric digestion. Nonetheless, intestinal digestion led to the degradation of proanthocyanidins (PAs) and a significant decrease in TPC (26%). Degradation was determined by normal-phase HPLC and gel permeation chromatography. Only monomers, dimers, and trimers of flavan-3-ols were identified in the serum-accessible fraction for characterization of their bioaccessibility. The results also indicated the obvious antioxidant capacity of PAs from A. mearnsii bark, and ~53% of the α-glucosidaseâ»inhibitory effect was preserved. All these findings show that PAs from A. mearnsii bark as a native plant source may be particularly beneficial for human health as a natural nutritional supplement.
Subject(s)
Acacia/chemistry , Plant Extracts/pharmacokinetics , Polyphenols/pharmacokinetics , Antioxidants/chemistry , Antioxidants/pharmacokinetics , Chromatography, High Pressure Liquid , Gastrointestinal Tract/metabolism , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacokinetics , In Vitro Techniques , Mass Spectrometry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/metabolism , Polyphenols/chemistry , Polyphenols/isolation & purification , Polyphenols/metabolism , Proanthocyanidins/chemistry , Proanthocyanidins/pharmacokinetics , Solid Phase ExtractionABSTRACT
The absorption and antioxidant activity of polyphenols from grape pomace (GP) are important aspects of its valorization as a feed additive in the diet of weaned piglets. This study aimed to evaluate the presence of polyphenols from GP both in vitro in IPEC cells and in vivo in the duodenum and colon of piglets fed with diets containing or not 5% GP and also to compare and correlate the aspects of their in vitro and in vivo absorption. Total polyphenolic content (TPC) and antioxidant status (TAS, CAT, SOD and GPx enzyme activity, and lipid peroxidation-TBARS level) were assessed in duodenum and colon of piglets fed or not a diet with 5% GP. The results of UV-Vis spectroscopy demonstrated that in cellular and extracellular medium the GP polyphenols were oxidized (between λmax = 276 nm and λmax = 627.0 nm) with the formation of o-quinones and dimers. LC-MS analysis indicated a procyanidin trimer possibly C2, and a procyanidin dimer as the major polyphenols identified in GP, 12.8% of the procyanidin trimer and 23% of the procyanidin dimer respectively being also found in the compound feed. Procyanidin trimer C2 is the compound accumulated in duodenum, 73% of it being found in the colon of control piglets, and 62.5% in the colon of GP piglets. Correlations exist between the in vitro and in vivo investigations regarding the qualitative evaluation of GP polyphenols in the cells (λmax at 287.1 nm) and in the gut (λmax at 287.5 nm), as oxidated metabolic products. Beside the presence of polyphenols metabolites this study shows also the presence of the unmetabolized procyanidin trimers in duodenum and colon tissue, an important point in evaluating the benefic actions of these molecules at intestinal level. Moreover the in vivo study shows that a 5% GP in piglet’s diet increased the total antioxidant status (TAS) and decreased lipid peroxidantion (TBARS) in both duodenum and colon, and increased SOD activity in duodenum and CAT and GPx activity in colon. These parameters are modulated by the different polyphenols absorbed, mainly by the procyanidin trimers and catechin on one side and the polyphenols metabolites on the other side.
Subject(s)
Intestinal Absorption/drug effects , Polyphenols/pharmacokinetics , Vitis/chemistry , Animals , Animals, Newborn , Antioxidants/pharmacokinetics , Biflavonoids/pharmacokinetics , Catalase/metabolism , Catechin/pharmacokinetics , Cell Survival/drug effects , Diet/veterinary , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Glutathione Peroxidase/metabolism , Intestine, Small/cytology , Intestine, Small/drug effects , Intestine, Small/metabolism , Lipid Peroxidation/drug effects , Plant Extracts/pharmacokinetics , Proanthocyanidins/pharmacokinetics , Superoxide Dismutase/metabolism , Swine , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
SCOPE: Several studies have demonstrated that flavan-3-ol/procyanidins are associated with biological functions in the prevention of various chronic diseases, including obesity and diabetes. Knowledge of their mechanisms, including bioavailability, has significantly progressed in the last decade. However, the differences of the metabolic signatures among flavan-3-ol/procyanidins remain ambiguous. METHODS AND RESULTS: The metabolites in urine over time after acute administration of three typical flavan-3-ol/procyanidins ((epi)catechin [EPC], epigallocatechin gallate [EGCG], and procyanidin dimer [PC]) in view of the chemical structure were analyzed by HPLC-quadrupole TOF/MS. Several bile acid and amino acid derivatives including tryptophan and tyrosine, as well as flavan-3-ol/procyanidin conjugates and phenolic acid degradation products generated by the gut microbiota were observed in rat urine. CONCLUSION: Multivariate statistical analyses suggest that the exogenous and endogenous metabolites of flavan-3-ol/procyanidins greatly differ, although the chemical structures of three typical flavan-3-ol/procyanidins-EPC, EGCG, and PC-are similar. Thus, metabolomic differences likely affect their biological functions and health benefits.
Subject(s)
Biflavonoids/urine , Catechin/analogs & derivatives , Catechin/urine , Proanthocyanidins/urine , Animals , Biflavonoids/administration & dosage , Biflavonoids/pharmacokinetics , Catechin/administration & dosage , Catechin/chemistry , Catechin/pharmacokinetics , Chromatography, High Pressure Liquid , Flavonoids/pharmacokinetics , Male , Mass Spectrometry/methods , Molecular Weight , Proanthocyanidins/administration & dosage , Proanthocyanidins/pharmacokinetics , Rats, WistarABSTRACT
OBJECTIVES: Over the past three decades, numerous studies have focused on the biological activities of oligomeric proanthocyanidins (OPCs) in the prevention of many diseases such as neurodegeneration, atherosclerosis, tumorigenesis, and microbial infections. OPC has redox-active metabolites which could modulate the intracellular redox equilibrium to maintain the antioxidant homeostasis. This redox-modulating efficiency of OPC could provide new insights into therapeutic approaches that could reduce the burden of cardiovascular diseases. The main objective of this study was to explore the biological and metabolic activities of OPC using in silico approaches. METHODS: To validate the above objective, chemoinformatic tools were used to predict the metabolism of OPC after ingestion, based on both the ligand and structure of the constituent compounds. RESULTS: OPC showed possible sites for Phase I metabolism by cytochrome P450, and the metabolites obtained thereafter may be responsible for its biological activities. Absorption, distribution, metabolism, elimination, and toxicity properties showed efficient absorption, distribution, and metabolism of OPC, without toxicity. CONCLUSION: Thus, from the results obtained, OPC could be strongly recommended as a cardioprotective drug.
Subject(s)
Cardiotonic Agents/pharmacokinetics , Computer Simulation , Proanthocyanidins/pharmacokinetics , Antioxidants/metabolism , Cardiotonic Agents/chemistry , Cardiotonic Agents/toxicity , Cytochrome P-450 Enzyme System/metabolism , Humans , Ligands , Oxidation-Reduction , Proanthocyanidins/chemistry , Proanthocyanidins/toxicityABSTRACT
Proanthocyanidins are a major group of flavonoids in the human diet, known for their strong antioxidant properties. Emerging evidence from clinical studies indicates a role of proanthocyanidins in modulating glucose homeostasis, and higher proanthocyanidin intake has been associated with reduced risk of diabetes. On the other hand, recent studies report limited bioavailability of proanthocyanidins. At relatively low concentrations in the systemic circulation, proanthocyanidins may act as cell-signaling molecules to modulate glucose homeostasis. For example, they affect hepatic glucose production via adenosine monophosphate-activated protein kinase and/or insulin-signaling pathways. There is also evidence for a direct role of proanthocyanidins in modulating several pancreatic ß-cell functions: prevention of oxidative stress, enhancement of insulin secretion, and promotion of ß-cell survival. Therefore, greater understanding of the potentially beneficial effects of proanthocyanidins on cell-signaling pathways implicated in glucose homeostasis is needed. In addition, further investigation to address the in vivo metabolism of proanthocyanidins and the comparative effectiveness of proanthocyanidin-derived metabolites is warranted. The dosage and the experimental model should be given special attention when results from mechanistic studies using proanthocyanidins are interpreted.