ZIF-8-modified hydrogel sequentially delivers angiogenic and osteogenic growth factors to accelerate vascularized bone regeneration.

To realize high-quality vascularized bone regeneration, we developed a multifunctional hydrogel (SHPP-ZB) by incorporating BMP-2@ZIF-8/PEG-NH2 nanoparticles (NPs) into a sodium alginate/hydroxyapatite/polyvinyl alcohol hydrogel loaded with PDGF-BB, allowing for the sequential release of angiogenic and osteogenic growth factors (GFs) during bone repair. ZIF-8 served as a protective host for BMP-2 from degradation, ensuring high encapsulation efficiency and long-term bioactivity. The SHPP-ZB hydrogel exhibited enhanced mechanical strength and injectability, making it suitable for complex bone defects. It provided a swelling interface for tissue interlocking and the early release of Zn2+ and tannin acid (TA) to exert antioxidant and antibacterial effects, followed by the sequential release of angiogenic and osteogenic GFs to promote high-quality vascularized bone regeneration. In vitro experiments demonstrated the superior angiogenic and osteogenic properties of SHPP-ZB compared to other groups. In vivo experiments indicated that the sequential delivery of GFs via SHPP-ZB hydrogel could improve vascularized bone regeneration. Further, RNA sequencing analysis of regenerative bone tissue revealed that SHPP-ZB hydrogel promoted vascularized bone regeneration by regulating JUN, MAPK, Wnt, and calcium signaling pathways in vivo. This study presented a promising approach for efficient vascularized bone regeneration in large-scale bone defects.

Chitosan-coated PLGA microemulsion loaded with tannic acid against Escherichia coli in vitro and in vivo.

The overuse of antibiotics has resulted in a surge of drug-resistant bacteria, making the pursuit of natural antimicrobials an urgent and significant trend. Encapsulation and nanoparticulation are effective ways to enhance the antibacterial properties of natural drugs. In this study, we encapsulated tannic acid (TA) with chitosan (CS) and poly (lactide-co-glycolide) (PLGA) using the emulsion-solvent evaporation method to enhance the antimicrobial effect of TA. We prepared a bilayer membrane spherical nanoemulsion of TA-PLGA-CS (TPC) with uniform size of 559.87 ± 1.16 nm, and zeta potential of 59.53 ± 1.07 mV. TPC could be stably stored for 90 days at 4°C without affecting the properties of the emulsion, and the minimum bactericidal concentration against four strains of Escherichia coli (E. coli) remained unchanged for 60 d. The results indicated that TPC enhanced the inhibitory effect of TA against E. coli. Scanning electron microscope images revealed that TPC treatment caused damage to the bacterial cell membrane. In addition, in vivo experiments indicated that TPC exhibited a superior therapeutic effect on artificial colibacillosis in chickens infested with Avian pathogenic Escherichia coli, as evidenced by the changes in body weight and a reduction bacterial load in heart. Furthermore, TPC reversed the down-regulation of catalase, glutathione peroxidase1 (GPX1), and GPX7 gene expression levels in intestinal tissues. Compared to the model group, TPC treatment elevated serum glutathione peroxidase activities and lowered myeloperoxidase and lactate dehydrogenase levels, offering antioxidant protection that was slightly better than that of doxycycline hydrochlorid group. In summary, we prepared a novel TA antimicrobial preparation with significant antioxidant potential and inhibitory effect against E. coli both in vitro and in vivo.

Effects of inclusion of the blend of essential oils, organic acids, curcumin, tannins, vitamin E, and zinc in the maternal diet, and of incubation temperature on early and late development of quail.

The maternal diet and egg incubation temperature are some of the factors that can influence the embryonic development and performance of the newly chicks at 15 d of age. This study evaluated the effects of adding a blend of organic acids, essential oils, curcumin, tannins, vitamin E, and zinc microencapsulated in to the diet of female quails (Coturnix coturnix japonica) on their productive, reproductive performance and redox parameters of their eggs and the interaction of maternal diet × incubation temperature on embryo (E16 and E18) and chicks development. At 98 d of age, 64 female quails with a mean body weight of 150 g ± 0.5 were distributed into two treatments: a Basal diet or a diet supplemented with blend (Sannimix). The eggs from each female were incubated at 37.5°C (Control) and 38.5°C (High Temperature) throughout the incubation period. After hatching, chicks were distributed in a 2 (maternal diet) × 2 (incubation temperature) factorial design. Female quails supplemented with Sannimix showed better productive and reproductive performance and produced higher-quality embryos. Their offspring had greater weight at hatch and at 15 d of age. The eggs and offspring of supplemented with Sannimix female quails showed better oxidative stability. At E16 and E18, High Temperature increased yolk sac utilization and gene expression of the growth hormone receptor (GHR). At E16, embryos from supplemented with Sannimix female quail had higher expression of insulin-like growth factor type I (IGFI) and heat shock protein 70 kDa genes. At 15 d of age, highest expression of the GHR and IGFI genes was observed in chicks from female quails fed the Sannimix diet, regardless of incubation temperature. Regarding the maternal diet × incubation temperature an improved result was observed for chicks from female quails fed with Sannimix even when eggs are exposed to High Temperature during the incubation. The supplementation of quail diets with blend Sannimix improves productive and reproductive performance, egg quality and their embryos, as well as their offspring quality.

Enhancing the Bioavailability of the Ellagitannin, Geraniin: Formulation, Characterization, and in vivo Evaluation.

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.

Safety evaluation and effects of dietary phlorotannins on the growth, health, and intestinal microbiota of Litopenaeus vannamei.

Phlorotannins are phenolic compounds with diverse biological activities, yet their efficacy in aquatic animals currently remains unclear. This investigation scrutinized the influence of phlorotannins on the growth, immunity, antioxidant capacity, and intestinal microbiota in Litopenaeus vannamei, concurrently evaluating the potential adverse effects of phlorotannins on L. vannamei. A base diet without phlorotannins supplementation was used as a control, and 4 groups of diets with different concentrations (0, 0.5, 1.0, 2.0 g kg-1) of phlorotannins were formulated and fed to juvenile shrimp (0.25 ± 0.01 g) for 60 days followed by a 24-h challenge with Vibrio parahaemolyticus with triplicate in each group. Compared with the control, dietary 2.0 g kg-1 phlorotannins significantly improved the growth of the shrimp. The activities of enzymes related to cellular immunity, humoral immunity, and antioxidants, along with a notable upregulation in the expression of related genes, significantly increased. After V. parahaemolyticus challenge, the cumulative survival rates of the shrimp demonstrated a positive correlation with elevated concentrations of phlorotannins. In addition, the abundance of Bacteroidetes and functional genes associated with metabolism increased in phlorotannins supplementation groups. Phlorotannins did not elicit any detrimental effects on the biological macromolecules or histological integrity of the hepatopancreas or intestines. Simultaneously, it led to a significant reduction in malondialdehyde content. All results indicated that phlorotannins at concentrations of 2.0 g kg-1 can be used as safe feed additives to promote the growth, stimulate the immune response, improve the antioxidant capacity and intestinal health of L. vannamei, and an protect shrimp from damage caused by oxidative stress.

Multidimensional opioid abuse deterrence using a nanoparticle-polymer hybrid formulation.

Misuse of prescription opioid drugs is the leading cause of the opioid crisis and overdose-related death. Abuse deterrent formulations (ADFs) have been developed to discourage attempts to tamper with the formulation and alter the ingestion methods. However, abusers develop complex extraction strategies to circumvent the ADF technologies. For comprehensive deterrence of drug abuse, we develop tannic acid nanoparticles (NPs) that protect encapsulated opioids from solvent extraction and thermal challenge (crisping), complementing the existing formulation strategy to deter injection abuse. Here, we develop a hybrid ADF tablet (NP-Tab), consisting of iron-crosslinked tannic acid NPs encapsulating thebaine (model opioid compound), xanthan gum, and chitosan (gel-forming polymers), and evaluate its performance in common abuse conditions. NP-Tab tampered by crushing and suspended in aqueous solvents forms an instantaneous gel, which is difficult to pull or push through a 21-gauge needle. NPs insulate the drug from organic solvents, deterring solvent extraction. NPs also promote thermal destruction of the drug to make crisping less rewarding. However, NP-Tab releases thebaine in the simulated gastric fluid without delay, suggesting that its analgesic effect may be unaffected if consumed orally as prescribed. These results demonstrate that NP-Tab can provide comprehensive drug abuse deterrence, resisting aqueous/organic solvent extraction, injection, and crisping, while retaining its therapeutic effect upon regular usage.

Tannic acid coated nanosuspension for oral delivery of chrysin intended for anti-schizophrenic effect in mice.

Chrysin is a flavonoid drug with numerous therapeutic activities. It suffers from low intestinal absorption owing to its hydrophobicity. Therefore, the aim of this study is to exploit the efficient technique of nanosuspension (NSP) to formulate chrysin-NSP coated with tannic acid (TA) to improve the solubility and anti-schizophrenic activity of chrysin. A 23 full factorial design was constructed where the independent factors were type of polymer, surfactant concentration (0.5 or 1 %) and the aqueous phase volume (5 or 15 mL), while the dependent responses were the particle size (PS) of the obtained formulation as well as the % chrysin dissolved after 2 h (Q2h). The optimum formulation (NSP-4) composed of 1 % PEG 400 and 1 % Cremophor RH40 in 15 mL aqueous phase. It achieved a PS and Q2h values of 108.00 nm and 38.77 %, respectively. NSP-4 was then coated with TA (TA-coated NSP-4) for further enhancement of chrysin solubility. TA-coated NSP-4 revealed PS and zeta potential values of 150 ± 14 nm and -32.54 ± 2.45 mV, respectively. After 6 h, chrysin dissolved % were 53.97 and 80.22 for uncoated NSP-4 and TA-coated NSP-4, respectively, compared with only 9.47 for free chrysin. The developed formulations and free chrysin were assessed regarding their effect on schizophrenia induced in mice by cuprizone (CPZ). Treatment with the developed formulations and free chrysin ameliorated demyelination and behavioral deficit induced by CPZ via elevating MBP and PI3K/PKC activities as well as reducing GFAP expression levels. The developed formulations and free chrysin inhibited Galactin-3 and TGF-ß expressions and stimulated GST antioxidant enzyme. Furthermore, they maintained the balances in glutamatergic and dopaminergic neurotransmission via modulation on neuregulin-1 and alleviated nuclear pyknosis and degeneration in the neurons. The order of activity was: TA-coated NSP-4 > NSP-4 > free chrysin.

Feeding tannins to dairy cows in different seasons improves the oxidative status of blood plasma and the antioxidant capacity of cheese.

The aim of the present study was to assess the dietary supplementation of tannins to grazing dairy cows in 2 seasons characterized by a good quality pasture (spring) or a poor-quality pasture (summer). The effects of dietary tannins were assessed on plasma antioxidant status and cytokines profile and on the antioxidant properties of cheese and cheese in vitro digestates. Fourteen lactating dairy cows were divided into 2 homogeneous groups (n = 7): a control group (CON), and an experimental group (TAN) receiving 150 g/head per day of tannins supplementation. The experiment was performed twice, in spring and in summer. The animals were free to graze on spontaneous pasture (spring) or on dry stubble (summer). Blood was sampled at the beginning (d 0), at the midpoint (d 11), and at the end (d 22) of the trial. Individual cheese was produced before the beginning (d -1) and at the end (d 22) of the trial from the milk collected from each cow. On blood plasma, the reactive oxygen metabolites (ROM), biological antioxidant potential (BAP), nonesterified fatty acids quantification, and cytokines profile in terms of IL-10, IL-8, IL-1ß, and IFN-γ were determined. Data on ROM demonstrated that tannins supplementation lowered oxidative stress both in spring and in summer. Accordingly, TAN diet increased BAP levels compared with the CON during summer trial. Thus, feeding tannins resulted in lower ratio between ROM and BAP (oxidative stress index) in both spring and summer. Cytokines' profile showed lower IL-1ß values in TAN group at d 22 during spring season, with a concomitant higher IL-10 level, during summer season. Moreover, TAN group had a lower level of IFN-γ in plasma than CON group, both in spring and in summer. On cheese samples, the in vitro digestion was performed and on cheese and cheese digestates (gastric and intestinal digestate) the free radical scavenging antioxidant activity was evaluated. The intestinal digestate fraction registered the highest antioxidant activity compared with cheese and gastric digestate, in both spring and summer seasons. Furthermore, an improvement of the antioxidant property of cheese and cheese digestates was found. Present data demonstrated that tannins supplementation contributed to reduce the oxidative stress of lactating dairy cows and showed an increase of anti-inflammatory cytokines ratio.

Facile formation of injectable quaternized chitosan/tannic acid hydrogels with antibacterial and ROS scavenging capabilities for diabetic wound healing.

The wound healing process of the diabetic wound is often hindered by excessive oxygen free radicals and infection. An ideal wound dressing should possess great reactive oxygen species (ROS) scavenging property and considerable antibacterial ability. In this study, we facilely constructed a novel hydrogel dressing with excellent ROS scavenging property and outstanding antibacterial performance by introducing tannic acid (TA) into quaternized chitosan (QCS) matrix. Attributing to the suitable physical crosslinking between TA and QCS, this QCS/TA hydrogel was endowed with injectable and self-healing properties, which could avoid the various external squeezing on the irregular shape by wound dressing. The results showed that it could promote coagulation, suppress inflammation and expedite collagen deposition in the skin defect model of diabetic rats. This study provides a facile and convenient method for constructing injectable hydrogel dressing, which has application potentials in the clinical management of diabetic wounds.

Extraction and Nano-Sized Delivery Systems for Phlorotannins to Improve Its Bioavailability and Bioactivity.

This review aims to provide an informative summary of studies on extraction and nanoencapsulation of phlorotannins to improve their bioavailability and bioactivity. The origin, structure, and different types of phlorotannins were briefly discussed, and the extraction/purification/characterization methods for phlorotannins were reviewed, with a focus on techniques to improve the bioactivities and bioavailability of phlorotannins via nano-sized delivery systems. Phlorotannins are promising natural polyphenol compounds that have displayed high bioactivities in several areas: anticancer, anti-inflammation, anti-HIV, antidiabetic, and antioxidant. This review aims to provide a useful reference for researchers working on developing better utilization strategies for phlorotannins as pharmaceuticals, therapeuticals, and functional food supplements.

Polyphenol rich extracts of Geranium L. species as potential natural antioxidant and antimicrobial agents.

OBJECTIVE: Plants and plant extracts are of great scientific interest due to the chemical diversity and pharmacological properties of present bioactive molecules. The Geranium L. species are widely used in ethnomedicine. In the current study, the total phenolic and tannin content, antioxidant and antimicrobial activity of methanol extracts of eight Geranium species were investigated. MATERIALS AND METHODS: The total phenolic and tannin content were determined by the FC method. Antioxidant capacity was evaluated in FRAP, DPPH, and biochemical assays, while antimicrobial activity was examined using the broth microdilution method. RESULTS: The high total phenolic (170.64-636.32 mg GAE/g dry extract) and tannin content (37.80-414.02 mg GAE/g DE), along with significant total antioxidant (FRAP values 1.13-8.80 mmol Fe2+/g) and DPPH radical scavenging activity (SC50 values 4.24-34.52 µg/mL) were observed. The prominent antioxidant capacity was confirmed in biochemical assays (OS values -1.47 - -13.02). The extracts exhibited significant antimicrobial activity against ATTC strains (MICs dominantly in the range of 12.5-200 µg/mL) as well as against clinical isolates of E. coli (MICs mostly 50 and 100 µg/mL). The pronounced antioxidant and antimicrobial activity can be due to the high phenolic content, particularly due to the presence of hydrolyzable tannins. CONCLUSIONS: Based on the high content of polyphenols, pronounced antioxidant and antimicrobial activities, the examined extracts are promising natural antioxidant and antimicrobial agents with the potential medicinal purpose and use as a functional food.

Effect of dietary tannin supplementation on cow milk quality in two different grazing seasons.

Extensive farming systems are characterized by seasons with different diet quality along the year, as pasture availability is strictly depending on climatic conditions. A number of problems for cattle may occur in each season. Tannins are natural polyphenolic compounds that can be integrated in cows' diet to overcome these seasonal problems, but little is known about their effect on milk quality according to the season. This study was designed to assess the effects of 150 g/head × day of tannin extract supplementation on proximate composition, urea, colour, cheesemaking aptitude, antioxidant capacity, and fatty acid (FA) profile of cow milk, measured during the wet season (WS) and the dry season (DS) of Mediterranean climate. In WS, dietary tannins had marginal effect on milk quality. Conversely, in DS, the milk from cows eating tannins showed 10% lower urea and slight improvement in antioxidant capacity, measured with FRAP and TEAC assays. Also, tannin extract supplementation in DS reduced branched-chain FA concentration, C18:1 t10 to C18:1 t11 ratio and rumenic to linoleic acid ratio. Tannins effect on rumen metabolism was enhanced in the season in which green herbage was not available, probably because of the low protein content, and high acid detergent fibre and lignin contents in diet. Thus, the integration of tannin in the diet should be adapted to the season. This could have practical implications for a more conscious use of tannin-rich extracts, and other tannin sources such as agro-industrial by-products and forages.

Tannic acid protects aged brain against cerebral hypoperfusion via modulation of Nrf2 and inflammatory pathways.

Current study purposed to investigate the neuroprotective effects of Tannic Acid (TA) on mild chronic cerebral hypoperfusion model in rats. Male Wistar rats were subjected to permanent Unilateral Common Carotid Artery Occlusion (UCCAO), followed by TA treatment (0.05% w/v) in drinking water for one month. Nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO-1), heme oxygenase-1 (HO-1), factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, blood triglyceride, blood glucose, and liver enzymes' activity were detected after the experimental period. Also, behavioral tests, hematoxylin and eosin (H&E) staining, and PET scan were performed after treatment. Post-treatment of TA improved locomotion and memory function (P < 0.001), and reduced neural cell death (P < 0.001) in the treatment group compared to UCCAO rats. Furthermore, long-term TA treatment significantly increased the levels of Nrf2 (P < 0.001), NQO-1 (P < 0.001), and HO-1 (P < 0.001) in the hippocampus of the treatment group compared to the UCCAO group. TA consumption in the treatment group applied its anti-inflammatory effects via reducing the activity of NF-κB and TNF-α in comparison with the UCCAO group (P < 0.001 for both). Blood triglyceride, blood glucose, and liver enzymes did not change considerably in the groups (P > 0.05). The current results indicate that long-term post-treatment of TA exhibits protective effects against memory deficit and motor dysfunction. The cellular mechanism of TA in hypoperfused rats might be associated with the activation of antioxidant pathways, especially the Nrf2 pathway, and suppressing inflammatory factors like NF-κB and TNF-α.

Mixture of Phlorotannin and Fucoidan from Ecklonia cava Prevents the Aß-Induced Cognitive Decline with Mitochondrial and Cholinergic Activation.

The anti-amnesic effect of a mixture (4:6 = phlorotannin:fucoidan from Ecklonia cava, P4F6) was evaluated on amyloid-beta peptide (Aß)-induced cognitive deficit mice. The cognitive function was examined by Y-maze, passive avoidance, and Morris water maze tests, and the intake of the mixture (P4F6) showed an ameliorating effect on Aß-induced learning and memory impairment. After the behavioral tests, superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) contents were confirmed in brain tissue, and in the results, the mixture (P4F6) attenuated Aß-induced oxidative stress. In addition, mitochondrial activity was evaluated by mitochondrial reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic signaling pathway, and the mixture (P4F6) enhanced mitochondrial function. Furthermore, the mixture (P4F6) effectively regulated tau hyperphosphorylation by regulating the protein kinase B (Akt) pathway, and promoted brain-derived neurotrophic factor (BDNF) in brain tissue. Moreover, in the cholinergic system, the mixture (P4F6) ameliorated acetylcholine (ACh) content by regulating acetylcholinesterase (AChE) activity and choline acetyltransferase (ChAT) expression in brain tissue. Based on these results, we suggest that this mixture of phlorotannin and fucoidan (P4F6) might be a substance for improving cognitive function by effectively regulating cognition-related molecules.

A mixture of quebracho and chestnut tannins drives butyrate-producing bacteria populations shift in the gut microbiota of weaned piglets.

Weaning is a critical period for piglets, in which unbalanced gut microbiota and/or pathogen colonisation can contribute to diseases that interfere with animal performance. Tannins are natural compounds that could be used as functional ingredients to improve gut health in pig farming thanks to their antibacterial, antioxidant, and antidiarrhoeal properties. In this study, a mixture of quebracho and chestnut tannins (1.25%) was evaluated for its efficacy in reducing the negative weaning effects on piglet growth. Microbiota composition was assessed by Illumina MiSeq 16S rRNA gene sequencing of DNA extracted from stools at the end of the trial. Sequence analysis revealed an increase in the genera Shuttleworthia, Pseudobutyrivibrio, Peptococcus, Anaerostipes, and Solobacterium in the tannin-supplemented group. Conversely, this dietary intervention reduced the abundance of the genera Syntrophococcus, Atopobium, Mitsuokella, Sharpea, and Prevotella. The populations of butyrate-producing bacteria were modulated by tannin, and higher butyrate concentrations in stools were detected in the tannin-fed pigs. Co-occurrence analysis revealed that the operational taxonomic units (OTUs) belonging to the families Veillonellaceae, Lachnospiraceae, and Coriobacteriaceae occupied the central part of the network in both the control and the tannin-fed animals. Instead, in the tannin group, the OTUs belonging to the families Acidaminococcaceae, Alcaligenaceae, and Spirochaetaceae characterised its network, whereas Family XIII Incertae Sedis occupied a more central position than in the control group. Conversely, the presence of Desulfovibrionaceae characterised the network of the control group, and this family was not present in the network of the tannin group. Moreover, the prediction of metabolic pathways revealed that the gut microbiome of the tannin group possessed an enhanced potential for carbohydrate transport and metabolism, as well as a lower abundance of pathways related to cell wall/membrane/envelope biogenesis and inorganic ion transport. In conclusion, the tested tannins seem to modulate the gut microbiota, favouring groups of butyrate-producing bacteria.

Persimmon-derived tannin ameliorates the pathogenesis of ulcerative colitis in a murine model through inhibition of the inflammatory response and alteration of microbiota.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) induced by dysregulation of the immune response in the intestinal mucosa. Although the underlying mechanisms of UC development are not fully understood, disruption of gut microbiota, "dysbiosis", is thought to lead to the development of IBD. Persimmon (Ebenaceae Diospyros kaki Thunb.)-derived tannin, which is a condensed polymeric tannin consisting of catechin groups, has antioxidant, anti-inflammatory, and antimicrobial activities. In this study, we assessed the effect of persimmon-derived tannin on a murine model of UC established by dextran sulfate sodium-induced colitis in female mice. Dietary supplementation of tannin significantly decreased disease activity and colon inflammation. A hydrolysate of tannin directly suppressed expression of inflammatory genes in macrophages in vitro. In faecal microbiota, the relative abundance of Bacteroides was increased significantly by tannin supplementation. Alpha-diversity indices in colitis-induced mice were significantly higher in the tannin diet group compared with the control diet group. Additionally, expansion of Enterobacteriaceae and Enterococcus, which is associated with disease progression of IBD, was remarkably suppressed in the tannin diet group. These results suggest that persimmon-derived tannin ameliorates colon inflammation in UC through alteration of the microbiota composition and immune response, which may be a promising candidate for IBD therapy.

Pyrogallol-Phloroglucinol-6 6-Bieckol on Attenuates High-Fat Diet-Induced Hypertension by Modulating Endothelial-to-Mesenchymal Transition in the Aorta of Mice.

Endothelial-to-mesenchymal transition (EndMT), which is involved in the development of various cardiovascular diseases, is induced by dyslipidemia or obesity. In dyslipidemia, the increased levels of oxidized low-density lipoproteins (oxLDL) upregulated the lectin-type oxidized LDL receptor 1 (Lox-1), which then upregulated the down signaling pathways of PKC-α/MMPs/TGF-ß/SMAD2 or 3 and increased the EndMT. In this study, we investigated the effect of pyrogallol-phloroglucinol-6,6-bieckol (PPB), which is a compound of Ecklonia cava (E. cava), on decreased blood pressure (BP) by attenuating the EndMT in a high-fat diet- (HFD-) fed animal model. We also investigated PPB's attenuation effect on EndMT in oxLDL-treated mouse endothelial cells as an in vitro model. The results indicated that, in the aorta or endothelial cells of mice, the HFD or oxLDL treatment significantly increased the expression of Lox-1/PKC-α/MMP9/TGF-ß/SMAD2/SMAD3. The PPB treatment significantly decreased its expression. In contrast, the HFD or oxLDL treatment significantly decreased the expression of the EC markers (PECAM-1 and vWF) while the PPB treatment significantly increased them. Moreover, the HFD or oxLDL treatment significantly increased the expression of the mesenchymal cell markers (α-SMA and vimentin) while PPB treatment significantly decreased them. PPB decreased the intima-media thickness and extracellular matrix amount of the aorta and attenuated the BP, which was increased by the HFD. In conclusion, PPB attenuated the upregulation of Lox-1/PKC-α/MMP9/TGF-ß/SMAD2 and 3 and restored the EndMT in HFD-fed animals. Moreover, PPB showed a restoring effect on HFD-induced hypertension.

Antioxidant activity and laxative effects of tannin-enriched extract of Ecklonia cava in loperamide-induced constipation of SD rats.

To investigate the role of tannin-enriched extracts of Ecklonia cava (TEE) on the regulation of oxidative balance and laxative activity in chronic constipation, we investigated alterations after exposure to TEE, on constipation phenotypes, muscarinic cholinergic regulation, and oxidative stress responses in the transverse colons of SD rats with loperamide (Lop)-induced constipation. This extract contains high levels of total condensed tannin content (326.5 mg/g), and exhibited high inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. TEE treatment induced significant improvements in reactive oxygen species (ROS) production, superoxide dismutase (SOD) expression and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation in primary smooth muscles of rat intestine cells (pRISMCs) and transverse colon of constipation model. Also, Lop+TEE treated groups showed alleviated outcomes for the following: most stool parameters, gastrointestinal transit, and intestine length were remarkably recovered; a similar recovery pattern was observed in the histopathological structure, mucin secretion, water channel expression and gastrointestinal hormones secretion in the transverse colon; expressions of muscarinic acetylcholine receptors M2/M3 (mAChR M2/M3) and their mediators on muscarinic cholinergic regulation were significantly recovered. Taken together, these results provide the first evidence that TEE stimulates oxidative stress modulation and muscarinic cholinergic regulation when exerting its laxative effects in chronic constipation models.

Prevention of the rise in plasma cholesterol and glucose levels by kaki-tannin and characterization of its bile acid binding capacity.

BACKGROUND: Bile acid-binding agents, such as cholestyramine and colesevelam, improve both cholesterol and glucose metabolism. Kaki-tannin, a polymerized condensed tannin derived from persimmon (Diospyros kaki), has been shown to have bile acid-binding capacity and a hypocholesterolemic effect. However, its effects on glucose metabolism have not been well studied, and the binding selectivity of kaki-tannin to bile acid molecules has not been reported. RESULTS: In vivo experiments using mice with high-fat diet-induced obesity showed that kaki-tannin intake (20 g kg-1 of the diet) increased fecal bile acid excretion by 2.3-fold and prevented a rise in plasma cholesterol levels and fasting plasma glucose levels. Kaki-tannin also suppressed the development of impaired glucose tolerance. To characterize the bile acid-binding capacity of kaki-tannin, we investigated its capacity to bind to eight types of bile acid and cholesterol in vitro. Kaki-tannin showed strong capacity to bind to lithocholic acid (85.5%), which has one hydroxy group. It also showed moderate capacity to bind to bile acids with two hydroxy groups (53.3%), followed by those with three hydroxy groups (39.0%), but kaki-tannin did not show binding capacity to cholesterol. These results suggest that the binding capacity of kaki-tannin to bile acids tends to decrease as the number of hydroxy groups increases. Interestingly, the binding capacity of kaki-tannin correlated with that of cholestyramine (correlation coefficient: r = 0.900). CONCLUSION: Our findings indicate that kaki-tannin binds preferentially to bile acids with fewer hydroxy groups and has beneficial effects on glucose metabolism as well as cholesterol metabolism. © 2020 Society of Chemical Industry.

In vitro impact of condensed tannins on the caecal metabolites of chickens / Impacto in vitro de taninos condensados nos metabólitos cecais de frangos de corte

Tannins are a diverse group of plant phenolic compounds. Condensed tannins (CTs) represent a major subgroup of tannins and were extracted from tilia (Tilia L.) flowers and black locust (Robinia pseudoacacia) leaves. These extracts were examined for their effects on the metabolic profile of chicken caeca. By using in vitro, a nuclear magnetic resonance (1H-NMR), which was combined with multivariate statistics, the current study was applied for the first time to investigate how three different CT compositions, procyanidins (PC) and/or prodelphinidins (PD) units influenced the metabolic end-products in caecal contents of chickens. In the presence of tannins, glutamate, leucine, lysine, pyroglutamate, phenylalanine, proline, and sarcosine were significantly decreased. CT extracts significantly influenced the fermentation, increasing the concentrations of some fatty acids such as acetate, butyrate, and propionate whereas. In contrast, lactate decreased between the treatments. This study identified the key structural features of CTs that contain either high molar proportions of PD or PC, which might be useful to improve the efficiency of feed utilization in chickens.(AU)

Taninos são um grupo diversificado de compostos fenólicos derivados de plantas. Os taninos condensados (TCs) representam o maior subgrupo de taninos extraídos das flores de tília (Tilia L) e de folhas negras (acácia-bastarda). Estes extratos foram examinados para a avaliação dos seus efeitos no perfil metabólico do ceco de frangos de corte. Com o emprego da ressonância magnética nuclear in vitro (1H-NMR) combinada com estatística multivariada, o presente trabalho foi aplicado pela primeira vez para investigar como três diferentes composições de TCs, unidades de procianidinas (PC) e/ou prodelfinidinas (PD) influenciariam os produtos metabólicos finais dos conteúdos cecais de frangos de corte. Na presença de taninos, houve um significativo decréscimo de glutamato, leucina, lisina, piroglutamato, fenilalanina, prolina e sarcosina. Os extratos de TCs influenciaram significativamente a fermentação, aumentando as concentrações de alguns ácidos graxos, tais como o acetato, butirato e propionato, enquanto em contraste, houve um decréscimo do lactato entre os tratamentos. Este trabalho identificou aspectos estruturais chave que os TCs contêm, tanto as altas proporções molares de PD como as de PC, as quais podem ser úteis para aumentar a utilização de alimentos em frangos de corte.(AU)