ABSTRACT
The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.
Subject(s)
Catechin , Deoxycytidine , Gemcitabine , Lung Neoplasms , Nanoparticles , Animals , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacokinetics , Deoxycytidine/administration & dosage , Deoxycytidine/chemistry , Mice , Catechin/analogs & derivatives , Catechin/administration & dosage , Catechin/pharmacokinetics , Catechin/chemistry , Nanoparticles/chemistry , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Tissue Distribution , Administration, Intranasal , Particle Size , Drug Liberation , Lipids/chemistry , Drug Carriers/chemistry , Male , LiposomesABSTRACT
Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium, resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.
Subject(s)
Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Animals , Inflammatory Bowel Diseases/drug therapy , Administration, Oral , Gastrointestinal Microbiome/drug effects , Mice , Catechin/analogs & derivatives , Catechin/chemistry , Catechin/administration & dosage , Catechin/pharmacology , Gallium/chemistry , Gallium/pharmacology , Disease Models, Animal , Inflammation/drug therapy , Reactive Oxygen Species/metabolism , Colitis/drug therapy , Humans , Reactive Nitrogen Species/metabolismABSTRACT
Green tea (GT) catechins exhibit antiviral effects in experimental studies. However, we lack clinical evidence on the preventive effects of catechin concentrations in gargling against acute upper respiratory tract infections (URTIs). Therefore, we aimed to investigate the concentration-dependence of GT catechins in gargling on the incidence of URTIs. We conducted an open-label randomized study. The target population consisted of 209 students from the University of Shizuoka and Meiji University, who were randomly assigned to high-catechin (approximate catechin concentration: 76.4 mg/dL), low-catechin (approximate catechin concentration: 30.8 mg/dL), and a control water gargling (catechin concentration: 0 mg/dL) group. All participants gargled water or GT daily for 12 weeks. The symptoms of URTIs were recorded on a daily survey form by participants. The incidences of URTIs occurred in 6 (9.1%), 7 (10.8%), and 11 (15.7%) participants in the high-catechin, low-catechin, and water groups, respectively. Cox proportional hazards analysis, using background factors and prevention status as covariates, revealed a hazard ratio of 0.57 (95% Confidence Interval (CI): 0.21-1.55, p = 0.261) for the high-catechin vs. water group and 0.54 (95% CI: 0.20-1.50, p = 0.341) for the low-catechin vs. water group. Our findings showed the incidence of URTIs in a concentration-dependent GT gargling was not significantly different, partly owing to the low event rates caused by intense precautions against the coronavirus disease 2019 pandemic. Our study would serve as a foundation for the development of an advanced protocol with optimal concentrations and a larger number of participants.
Subject(s)
Catechin , Respiratory Tract Infections , Tea , Catechin/pharmacology , Catechin/therapeutic use , Catechin/administration & dosage , Humans , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/epidemiology , Male , Female , Tea/chemistry , Young Adult , Adult , Dose-Response Relationship, Drug , Acute Disease , Incidence , Antiviral Agents/therapeutic useABSTRACT
The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl3)-induced rat model of Alzheimer's disease (AD). The Catechin-loaded Chitosan-Alginate nanocarriers were synthesized through ionotropic gelation (IG) method. Physio-chemical characterization was conducted with the Zetasizer Nano system, the scanning electron microscope, and the Fourier transform infrared spectroscopy. The experiments were performed over 21 days on six groups of male Wistar rats. The control group, AlCl3 treated group, Catechin group, nanocarrier group, treatment group 1 (AlCl3 + Catechin), and treatment group 2 (AlCl3 + nanocarrier). A behavioral study was done by the Morris water maze (MWM) test. In addition, the level of oxidative indices and acetylcholine esterase (AChE) activity was determined by standard procedures at the end of the study. AlCl3 induced a significant increase in AChE activity, along with a significant decrease in the level of Catalase (CAT) and total antioxidant capacity (TAC) in the hippocampus. Moreover, the significant effect of AlCl3 was observed on the behavioral parameters of the MWM test. Both forms of Catechin markedly improved AChE activity, oxidative biomarkers, spatial memory, and learning. The present study indicated that the administration of Catechin-loaded Chitosan-Alginate NPs is a beneficial therapeutic option against behavioral and chemical alteration of AD in male Wistar rats.
Subject(s)
Alginates , Aluminum Chloride , Alzheimer Disease , Catechin , Chitosan , Nanoparticles , Rats, Wistar , Animals , Catechin/administration & dosage , Catechin/pharmacology , Aluminum Chloride/toxicity , Chitosan/chemistry , Chitosan/administration & dosage , Alginates/chemistry , Alginates/administration & dosage , Male , Alzheimer Disease/drug therapy , Alzheimer Disease/chemically induced , Alzheimer Disease/metabolism , Rats , Administration, Oral , Cognition/drug effects , Acetylcholinesterase/metabolism , Maze Learning/drug effects , Hippocampus/drug effects , Hippocampus/metabolism , Disease Models, Animal , Antioxidants/pharmacology , Antioxidants/administration & dosage , Oxidative Stress/drug effects , Drug Carriers/chemistryABSTRACT
Multidrug-resistant (MDR) bacteria-infected wound healing remains greatly challenging, especially in diabetic patients. Herein, a novel nano-drug delivery based on endogenous glucose-driven cascade reaction is proposed for boosting MDR bacteria-infected diabetic wound healing with high efficacy by improving wound microenvironment and enhancing photodynamic antibacterial activity. The composite nanoagent is first self-assembled by integrating berberine (BBR) and epigallocatechin gallate (EGCG) from natural plant extracts, named as BENPs, which is successively coated with manganese dioxide nanoshells (MnO2 NSs) and glucose oxidase (GOX) to form the final BEMGNPs. The cascade reaction is triggered by glucose at the wound site of diabetes which is specifically catalyzed by GOX in the BEMGNPs to produce gluconic acid and hydrogen peroxide (H2O2). That is subsequently to decompose MnO2 NSs in the BEMGNPs to generate oxygen (O2). The BEMGNPs as photosensitizers effectively produce reactive oxygen species (ROS) to enhance the eradication of bacteria with the assistance of O2. Under the synergistic function of the cascaded reaction, the BEMGNPs present excellent antibacterial efficacy even for MDR bacteria. The in vivo experiments explicitly validate that the constructed nano-drug delivery can augment the MDR bacteria-infected diabetic wound healing with excellent biosafety. The as-proposed strategy provides an instructive way to combat ever-threatening MDR bacteria, which particularly is beneficial for diabetic patients.
Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Glucose , Manganese Compounds , Oxides , Wound Healing , Wound Healing/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Oxides/chemistry , Oxides/pharmacology , Glucose/chemistry , Glucose/metabolism , Drug Resistance, Multiple, Bacterial/drug effects , Animals , Glucose Oxidase/chemistry , Glucose Oxidase/pharmacology , Glucose Oxidase/metabolism , Catechin/chemistry , Catechin/pharmacology , Catechin/analogs & derivatives , Catechin/administration & dosage , Mice , Berberine/pharmacology , Berberine/chemistry , Microbial Sensitivity Tests , Diabetes Mellitus, Experimental/drug therapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Escherichia coli/drug effects , Particle Size , Humans , Nanoparticles/chemistry , Nanoparticle Drug Delivery System/chemistry , Nanoparticle Drug Delivery System/pharmacology , Staphylococcus aureus/drug effectsABSTRACT
BACKGROUND AND PURPOSE: Epigallocatechin gallate (EGCG), a natural antioxidant, has shown protective effect in many diseases. We explore the effect and potential regulatory mechanisms of EGCG in preeclampsia (PE)-like rats. METHODS AND MATERIALS: PE was mimicked in pregnant rats. EGCG was orally administered at a dosage of 25(Low, L) or 50â¯mg/kg (High, H) from gestational day (GD) 6-17. The blood pressure signatures, heart rates were monitored. The 24-h proteinuria and serum were analyzed. On GD 18, rats were sacrificed, and pups and placentas were weighed. Kidneys and placentas were analyzed using immunohistochemistry (IHC) and hematoxylin-eosin staining (H&E). Placentas were examined using western blot for sFlt1, eNOS, Nrf2, HO-1, SLC7A11. MDA, GSH, GPx and Fe2+ were measured. RESULTS: EGCG inhibits systolic blood pressure, BUN, CREA, ALT, AST, UA and proteinuria levels in PE-like rats. EGCG enhances the pup weight and crown-rump length and reduces the rate of fetus growth restriction in PE group. Endothelial dysfunction and infiltration of inflammatory cells were found in kidney cortex and placenta tissues in PE group and were inhibited by EGCG treatment. sFlt1 was activated in placentas in PE group and inhibited by EGCG while eNOS/Nrf2/HO-1 were inhibited in PE group and restored by EGCG. MDA and Fe concentrations were elevated in PE group and reduced by EGCG while the GSH level, SLC7A11 and the GPx activity were inhibited in PE group and restored by EGCG. CONCLUSION: EGCG alleviates inflammation, endothelial dysfunction and placental ferroptosis, improves pregnancy outcomes in PE-like rats via eNOS/Nrf2/HO-1.
Subject(s)
Catechin , NF-E2-Related Factor 2 , Nitric Oxide Synthase Type III , Pre-Eclampsia , Animals , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/administration & dosage , Pregnancy , Female , NF-E2-Related Factor 2/metabolism , Pre-Eclampsia/drug therapy , Pre-Eclampsia/immunology , Pre-Eclampsia/pathology , Rats , Nitric Oxide Synthase Type III/metabolism , Signal Transduction/drug effects , Signal Transduction/immunology , Disease Models, Animal , Placenta/drug effects , Placenta/pathology , Placenta/metabolism , Pregnancy Outcome , Humans , Inflammation/drug therapy , Inflammation/immunology , Rats, Sprague-Dawley , Heme Oxygenase (Decyclizing)/metabolismABSTRACT
The delivery of proteins into the cytosol holds great promise for cell signaling manipulation and the development of precision medicine. However, this potency is challenged by achieving targeted and controlled delivery, specifically within diseased cells. In this study, we introduce a versatile and effective method for the precision delivery of therapeutic proteins to cancer cells by designing polyphenol-assisted biomineralization of zeolite imidazole framework-8 (ZIF-8). We demonstrate that by leveraging the strong noncovalent binding affinity of epigallocatechin gallate (EGCG) with both proteins and ZIF-8, our approach significantly enhances the biomineralization of ZIF-8, which in turn improves the efficiency of protein encapsulation and intracellular delivery. Moreover, the incorporation of EGCG within ZIF-8 enables controlled degradation of the nanoparticles and the selective release of the encapsulated proteins in cancer cells. This selective release is triggered by the oxidation of EGCG in response to the high levels of reactive oxygen species (ROS) found within cancer cells that destabilize the EGCG/ZIF-8 nanoparticles. We have further demonstrated the ability of EGCG/ZIF-8 to deliver a wide range of proteins into cancer cells, including bacterial virulence protein, to rewire cell signaling and prohibit tumor cell growth in a mouse xenograft model. Our strategy and findings underscore the potential of designing the EGCG/ZIF-8 interface for specific and controlled protein delivery for targeted cancer therapy.
Subject(s)
Catechin , Metal-Organic Frameworks , Nanoparticles , Polyphenols , Humans , Metal-Organic Frameworks/chemistry , Polyphenols/chemistry , Polyphenols/pharmacology , Animals , Nanoparticles/chemistry , Catechin/analogs & derivatives , Catechin/chemistry , Catechin/administration & dosage , Catechin/pharmacology , Mice , Zeolites/chemistry , Biomineralization , Imidazoles/chemistry , Cell Line, Tumor , Neoplasms/drug therapy , Neoplasms/metabolism , Drug Delivery Systems/methods , Reactive Oxygen Species/metabolismABSTRACT
Theaflavin-3,3'-digallate (TFDG) in black tea has a strong antioxidant capacity. However, its effect on diabetic liver and kidney injury and the underlying mechanisms remain unclear. In the present study, our findings indicated that TFDG administration effectively lowers the fasting blood glucose and serum lipid concentrations and enhances the functionality and cellular architecture of the liver and kidney in rats with diabetes. The data also showed that TFDG mitigates oxidative harm in the liver and kidney of rats afflicted with diabetes. Additionally, metformin combined with TFDG was significantly more effective in reducing blood glucose and oxidative stress. Further studies suggested that TFDG upregulates the Nrf2 signal pathway and circ-ITCH (hsa_circ_0001141) expression. Silencing of circ-ITCH by transfection of the interfering plasmid apparently reduces the effects of TFDG on the Nrf2 signal pathway and oxidative stress in high-glucose-treated hepatic and renal cells. In conclusion, the present study highlights the great potential of TFDG in ameliorating diabetic liver and kidney injury by up-regulating circ-ITCH to promote the Nrf2 signal pathway and provides a potential option for the prevention and treatment of diabetic complications.
Subject(s)
Biflavonoids , Catechin , Kidney , Liver , NF-E2-Related Factor 2 , Oxidative Stress , Signal Transduction , Up-Regulation , Animals , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Rats , Biflavonoids/pharmacology , Catechin/analogs & derivatives , Catechin/administration & dosage , Catechin/pharmacology , Male , Liver/metabolism , Liver/drug effects , Signal Transduction/drug effects , Kidney/metabolism , Kidney/drug effects , Humans , Oxidative Stress/drug effects , Up-Regulation/drug effects , Rats, Sprague-Dawley , Protective Agents/administration & dosage , Protective Agents/pharmacology , Blood Glucose/metabolism , Camellia sinensis/chemistry , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/drug therapyABSTRACT
Desminopathy R350P is a human myopathy that is characterized by the progressive loss of muscle fiber organization. This results in the loss of muscle size, mobility, and strength. In desminopathy, inflammation affects muscle homeostasis and repair, and contributes to progressive muscle deterioration. Mitochondria morphology was also suggested to affect desminopathy progression. Epicatechin (Epi)-a natural compound found in cacao-has been proposed to regulate inflammatory signaling and mitochondria morphology in human and animal models. Hence, we hypothesize chronic Epi consumption to improve inflammatory pathway and mitochondria morphology in the peripheral blood mononuclear cells (PBMCs) of a desminopathy R350P patient. We found that 12 weeks of Epi consumption partially restored TRL4 signaling, indicative of inflammatory signaling and mitochondria morphology in the desminopathy patient. Moreover, Epi consumption improved blood health parameters, including reduced HOMA-IR and IL-6 levels in the desminopathy patient. This indicates that Epi consumption could be a useful tool to slow disease progression in desminopathy patients.
Subject(s)
Catechin , Leukocytes, Mononuclear , Mitochondria , Humans , Catechin/pharmacology , Catechin/administration & dosage , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/drug effects , Mitochondria/metabolism , Mitochondria/drug effects , Mitochondria/pathology , Male , Muscular Dystrophies/metabolism , Muscular Dystrophies/pathology , Muscular Dystrophies/drug therapy , Muscular Dystrophies/genetics , Adult , Female , Inflammation/metabolism , Inflammation/pathology , Cardiomyopathies/metabolism , Cardiomyopathies/pathology , Cardiomyopathies/drug therapy , Desmin/metabolism , Desmin/geneticsABSTRACT
Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core-shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm2), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In vivo therapeutic effect was evaluated using a S. aureus-infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.
Subject(s)
Anti-Bacterial Agents , Antioxidants , Catechin , Catechin/analogs & derivatives , Escherichia coli , Ferrocyanides , Nanoparticles , Polymers , Reactive Oxygen Species , Staphylococcus aureus , Catechin/chemistry , Catechin/pharmacology , Catechin/administration & dosage , Ferrocyanides/chemistry , Animals , Reactive Oxygen Species/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Rats , Polymers/chemistry , Nanoparticles/chemistry , Antioxidants/pharmacology , Antioxidants/administration & dosage , Antioxidants/chemistry , Male , Rats, Sprague-Dawley , Humans , Staphylococcal Infections/drug therapy , Mice , Photothermal Therapy/methods , Oxidative Stress/drug effectsABSTRACT
We aimed to study the potential of epigallocatechin-3-gallate/tyrosol-loaded chitosan/lecithin nanoparticles (EGCG/tyrosol-loaded C/L NPs) in streptozotocin-induced type 2 diabetes mellitus (T2DM) mice. The EGCG/tyrosol-loaded C/L NPs were created using the self-assembly method. Dynamic light scattering, Field Emission Scanning Electron Microscopy, and Fourier transform infrared spectroscopy were utilized to characterize the nanoparticle. Furthermore, in streptozotocin-induced T2DM mice, treatment with EGCG/tyrosol-loaded C/L NPs on fasting blood sugar levels, the expression of PCK1 and G6Pase, and IL-1ß in the liver, liver glutathione content, nanoparticle toxicity on liver cells, and liver reactive oxygen species were measured. Our findings showed that EGCG/tyrosol-loaded C/L NPs had a uniform size distribution, and encapsulation efficiencies of 84 % and 89.1 % for tyrosol and EGCG, respectively. The nanoparticles inhibited PANC-1 cells without affecting normal HFF cells. Furthermore, EGCG/tyrosol-loaded C/L NP treatment reduced fasting blood sugar levels, elevated hepatic glutathione levels, enhanced liver cell viability, and decreased reactive oxygen species levels in diabetic mice. The expression of gluconeogenesis-related genes (PCK1 and G6 Pase) and the inflammatory gene IL-1ß was downregulated by EGCG/tyrosol-loaded C/L NPs. In conclusion, the EGCG/tyrosol-loaded C/L NPs reduced hyperglycemia, oxidative stress, and inflammation in diabetic mice. These findings suggest that EGCG/tyrosol-loaded C/L NPs could be a promising therapeutic option for type 2 diabetes management.
Subject(s)
Catechin , Chitosan , Diabetes Mellitus, Experimental , Hyperglycemia , Liver , Nanoparticles , Animals , Chitosan/chemistry , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/administration & dosage , Diabetes Mellitus, Experimental/drug therapy , Nanoparticles/chemistry , Mice , Liver/drug effects , Liver/metabolism , Liver/pathology , Hyperglycemia/drug therapy , Male , Blood Glucose , Streptozocin , Reactive Oxygen Species/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Humans , Glutathione/metabolismABSTRACT
Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons. A randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 19, 34 ± 2 years) and adults with MetS (n = 21, 40 ± 3 years) examined 4-week administration of a decaffeinated GTE confection (890 mg/d total catechins) on serum endotoxin, intestinal permeability, gut and systemic inflammation, and cardiometabolic parameters. Compared with the placebo, the GTE confection decreased serum endotoxin (P = .023) in both healthy persons and those with MetS, while increasing concentrations of circulating catechins (P < .0001) and γ-valerolactones (P = .0001). Fecal calprotectin (P = .029) and myeloperoxidase (P = .048) concentrations were decreased by GTE regardless of health status. Following the ingestion of gut permeability probes, urinary lactose/mannitol (P = .043) but not sucralose/erythritol (P > .05) was decreased by GTE regardless of health status. No between-treatment differences (P > .05) were observed for plasma aminotransferases, blood pressure, plasma lipids, or body mass nor were plasma tumor necrosis factor-α, interleukin-6, or the ratio of lipopolysaccharide-binding protein/soluble cluster of differentiation-14 affected. However, fasting glucose in both study groups was decreased (P = .029) by the GTE confection compared with within-treatment arm baseline concentrations. These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation.
Subject(s)
Acute-Phase Proteins , Blood Glucose , Carrier Proteins , Catechin , Cross-Over Studies , Endotoxins , Inflammation , Membrane Glycoproteins , Metabolic Syndrome , Permeability , Plant Extracts , Tea , Humans , Metabolic Syndrome/drug therapy , Double-Blind Method , Endotoxins/blood , Adult , Male , Female , Plant Extracts/pharmacology , Tea/chemistry , Catechin/pharmacology , Catechin/analogs & derivatives , Catechin/administration & dosage , Inflammation/drug therapy , Inflammation/blood , Blood Glucose/metabolism , Blood Glucose/drug effects , Endotoxemia/drug therapy , Fasting , Middle Aged , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Camellia sinensis/chemistryABSTRACT
Postoperative abdominal adhesions are a common clinical problem after surgery and can cause many serious complications. Current most commonly used antiadhesion products are less effective due to their short residence time and focus primary on barrier function. Herein, we developed a sprayable hydrogel barrier (sHA-ADH/OHA-E) with self-regulated drug release based on ROS levels at the trauma site, to serve as a smart inflammatory microenvironment modulator and GATA6+ macrophages trap for non-adherent recovery from abdominal surgery. Sulfonated hyaluronic acid (HA) conjugates modified with adipic dihydrazide (sHA-ADH), and oxidized HA conjugates grafted with epigallocatechin-3-gallate (EGCG) via ROS-cleavable boronate bonds (OHA-E) were synthesized. sHA-ADH/OHA-E hydrogel was facilely fabricated within 5 s after simply mixing sHA-ADH and OHA-E through forming dynamic covalent acylhydrazones. With good biocompatibility, appropriate mechanical strength, tunable shear-thinning, self-healing, asymmetric adhesion, and reasonable in vivo retention time, sHA-ADH/OHA-E hydrogel meets the requirements of a perfect physical barrier. Intriguingly, sulfonic acid groups endowed the hydrogel with satisfactory anti-fibroblast and macrophage attachment capability, and were demonstrated for the first time to act as polyanion traps to prevent GATA6+ macrophages aggregation. Importantly, EGCG could be intelligently released by ROS triggering to alleviate oxidative stress and promote proinflammatory M1 macrophage polarize to antiinflammatory M2 phenotype. Further, the fibrinolytic system balance was restored to reduce fibrosis. Thanks to the above advantages, the sHA-ADH/OHA-E hydrogel exhibited excellent anti-adhesion effects in a rat sidewall defect-cecum abrasion model and is expected to be a promising and clinically translatable antiadhesion barrier.
Subject(s)
GATA6 Transcription Factor , Hyaluronic Acid , Hydrogels , Macrophages , Postoperative Complications , Reactive Oxygen Species , Tissue Adhesions/prevention & control , Animals , Hydrogels/chemistry , Hydrogels/administration & dosage , Macrophages/drug effects , Macrophages/metabolism , Reactive Oxygen Species/metabolism , Hyaluronic Acid/chemistry , Postoperative Complications/prevention & control , GATA6 Transcription Factor/metabolism , Catechin/analogs & derivatives , Catechin/chemistry , Catechin/administration & dosage , Catechin/pharmacology , Rats, Sprague-Dawley , Mice , Adipates/chemistry , Male , Abdomen/surgery , RAW 264.7 Cells , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Drug LiberationABSTRACT
Elevated glucose levels, multiple pro-inflammatory cytokines and the generation of excessive reactive oxygen species (ROS) are pivotal characteristics within the microenvironments of chronic periodontitis with diabetes mellitus (CPDM). Control of inflammation and modulation of immune system are required in the initial phase of CPDM treatment, while late severe periodontitis requires a suitable scaffold to promote osteogenesis, rebuild periodontal tissue and reduce alveolar bone resorption. Herein, a whole-course-repair system is introduced by an injectable hydrogel using phenylboronic acid functionalized oxidized sodium alginate (OSA-PBA) and carboxymethyl chitosan (CMC). Epigallocatechin-3-gallate (EGCG) was loaded to simultaneously adjust the mechanical property of the OSA-PBA/CMC + EGCG hydrogel (OPCE). This hydrogel has distinctive adaptability, injectability, and ROS/glucose-triggered release of EGCG, making it an ideal drug delivery carrier. As expected, OPCE hydrogel shows favourable antioxidant and anti-inflammatory properties, along with a regulatory influence on the phenotypic transition of macrophages, providing a favourable immune microenvironment. Apart from that, it provides a favourable mechanical support for osteoblast/osteoclast differentiation regulation at the late proliferation stage of periodontal regeneration. The practical therapeutic effects of OPCE hydrogels were also confirmed when applied for treating periodontitis in diabetic rats. In summary, OPCE hydrogel may be a promising whole-course-repair system for the treatment of CPDM.
Subject(s)
Catechin , Chronic Periodontitis , Diabetes Mellitus, Experimental , Drug Delivery Systems , Glucose , Reactive Oxygen Species , Glucose/metabolism , Reactive Oxygen Species/metabolism , Chronic Periodontitis/complications , Chronic Periodontitis/drug therapy , Diabetes Mellitus, Experimental/complications , Animals , Rats , Catechin/administration & dosage , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/therapeutic use , Rheology , Hydrogels , Antioxidants/metabolism , Macrophages/drug effects , Inflammation/drug therapy , Osteoclasts/cytology , Osteoblasts/cytology , Cell Differentiation , Bone Regeneration/drug effects , X-Ray Microtomography , Alveolar Bone Loss/drug therapy , Drug Delivery Systems/methods , Alginates , Schiff Bases , Male , Rats, Sprague-Dawley , RAW 264.7 Cells , MiceABSTRACT
Cardiomyopathy is one of complications related to diabetes. Stem cell transplantation shows potential in diabetic cardiomyopathy treatment. Epigallocatechin-3-gallate (EGCG) is one of the major components found in green tea. Although stem cell transplantation and green tea EGCG supplementation show therapeutic effects on cardiomyopathy, the detailed cellular mechanisms in stem cell transplantation coupled with EGCG treatment remain unclear. This study investigates whether adipose-derived stem cells (ADSC) pretreated with EGCG show better protective effect on diabetic cardiomyopathy than ADSC without EGCG pretreatment. A cell model indicated that ADSC pretreated with EGCG increased cell functions including colony formation, migration and survival markers. All of these functions are blocked by small interfering C-X-C motif chemokine receptor 4 (siCXCR4) administration. These findings suggest that ADSC pretreatment with EGCG increases cell functions through CXCR4 expression. A diabetic animal model was designed to verify the above findings, including Sham, DM (diabetes mellitus), DM+ADSC (DM rats receiving autologous transplantation of ADSC) and DM+E-ADSC (DM rats receiving EGCG pretreated ADSC). Compared to the Sham, we found that all of pathophysiological signalings were activated in the DM group, including functional changes (decrease in ejection fraction and fractional shortening), structural changes (disarray and fibrosis) and molecular changes (increases in apoptotic, fibrotic, hypertrophic markers and decreases in survival and longevity markers). E-ADSC (DM+E-ADSC) transplantation shows significant improvement in the above pathophysiological signalings greater than ADSC (DM+ADSC). Therefore, ADSC pretreated with EGCG may contribute to clinical applications for diabetic patients with cardiomyopathy.
Subject(s)
Catechin , Diabetic Cardiomyopathies , Receptors, CXCR4 , Tea , Animals , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/administration & dosage , Diabetic Cardiomyopathies/therapy , Tea/chemistry , Receptors, CXCR4/metabolism , Male , Adipose Tissue/cytology , Rats, Sprague-Dawley , Transplantation, Autologous , Rats , Stem Cell Transplantation , Disease Models, Animal , Stem Cells , Regeneration/drug effects , Diabetes Mellitus, Experimental/therapyABSTRACT
Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.
O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.
Subject(s)
Humans , /therapeutic use , Apoptosis/drug effects , Catechin/administration & dosage , Colorectal Neoplasms/drug therapy , Quercetin/administration & dosageABSTRACT
This study aimed to explore the potential regulatory pathways of (-)-epigallocatechin-3-gallate (EGCG) in preventing obesity-related precocious puberty. A retrospective analysis on the impact of EGCG on puberty onset in obese girls was conducted on plasma samples collected from a human randomized controlled trial. In the trial, participants consumed EGCG capsules for 12 weeks. In the animal experiment, rats were divided into four groups: normal diet control (NC) group, high-fat diet (HFD) group, NC+EGCG group, and HFD+EGCG group. Blood samples were collected on postnatal days 27, 33, and 36 to detect sexual development indicators. The hypothalamic expressions of kisspeptin/Kiss1R and neurokinin B (NKB)/NK3R signaling were measured by RT-qPCR and Western blot assay. The ovary NKB protein expression was assessed by immunohistochemical assays. Serum NKB level in the EGCG group was lower than the placebo group by 0.599 ng/mL [ß=-0.599, 95% CI: (-1.005, -0.193)], at the end of intervention and after adjusting for confounders (clinical study). In the animal experiment, EGCG intervention could significantly delay the vaginal opening (VO) time of rats fed with HFD. On day 33, EGCG intervention could significantly reduce serum NKB, luteinizing hormone (LH) levels, ovarian NKB protein expression, and endometrial thickness of HFD-fed rats, while EGCG intervention could remarkably increase mRNA and protein expression of NKB/NK3R. EGCG could prevent obesity-related precocious puberty through NKB/NK3R signaling pathway, which may provide a novel insight into the role of EGCG in preventing precocious puberty in obese girls.
Subject(s)
Camellia sinensis , Catechin , Obesity , Puberty, Precocious , Animals , Camellia sinensis/chemistry , Catechin/administration & dosage , Catechin/analogs & derivatives , Catechin/pharmacology , Female , Humans , Neurokinin B/genetics , Neurokinin B/metabolism , Obesity/complications , Puberty, Precocious/etiology , Puberty, Precocious/prevention & control , Rats , Retrospective Studies , Signal TransductionABSTRACT
CONTEXT: Epigallocatechin-3-O-gallate (EGCG) exhibits anti-arthritic activity. MiR-29b-3p provokes chondrocyte apoptosis and promotes the initiation and development of osteoarthritis (OA). OBJECTIVE: To explore the roles of EGCG and miR-29b-3p in interleukin-1ß (IL-1ß)-stimulated chondrocytes. MATERIALS AND METHODS: HE and Safranin O staining were used to detect the pathological changes of cartilage tissue in OA patients and healthy people. OA-like chondrocyte injury was mimicked by 5 ng/mL IL-1ß stimulation for 24 h in vitro, and after transfection with miR-29b-3p mimics and pcDNA-PTEN, IL-1ß-stimulated chondrocytes were pre-treated with EGCG (20 and 50 µM) for 2 h. Cell viability, colony numbers, apoptosis rate, the levels of IL-6 and matrix metalloproteinase-13 (MMP-13), miR-19b-3p, PTEN and apoptosis-associated proteins in chondrocytes were evaluated. RESULTS: MiR-29b-3p level was upregulated in cartilage tissues of OA patients (3.5-fold change, p < 0.001) and IL-1ß stimulated chondrocytes (two fold change, p < 0.001). The matrix staining was weakened and unevenly distributed, and the chondrocytes were arranged disorderly in the tissues of patients with OA. EGCG (20 and 50 µM) increases viability and decreases the levels of miR-29b-3p and MMP-13 and IL-6 in IL-1ß stimulated chondrocytes (p < 0.05). MiR-29b-3p mimics reversed the effects above 50 µM EGCG (p < 0.05). Furthermore, PTEN overexpression abrogated the effects of miR-29b-3p mimics on viability, colony numbers, apoptosis rate and the levels of Bcl-2, MMP-13, IL-6, Bax and cleaved caspase 3 in IL-1ß-stimulated chondrocytes (p < 0.01). DISCUSSION AND CONCLUSIONS: EGCG is a potential candidate for the treatment of OA, which also can be explored in a novel therapeutic method for other degenerative or inflammatory disorders.
Subject(s)
Catechin/analogs & derivatives , Chondrocytes/drug effects , Inflammation/prevention & control , Osteoarthritis/drug therapy , Adult , Aged , Apoptosis/drug effects , Case-Control Studies , Catechin/administration & dosage , Catechin/pharmacology , Cell Line , Chondrocytes/pathology , Dose-Response Relationship, Drug , Extracellular Matrix/drug effects , Humans , Inflammation/pathology , Interleukin-1beta/metabolism , MicroRNAs/genetics , Middle Aged , Osteoarthritis/pathology , PTEN Phosphohydrolase/genetics , Up-RegulationABSTRACT
Bone abnormalities affect all individuals with Down syndrome (DS) and are linked to abnormal expression of DYRK1A, a gene found in three copies in people with DS and Ts65Dn DS model mice. Previous work in Ts65Dn male mice demonstrated that both genetic normalization of Dyrk1a and treatment with ~9 mg/kg/day Epigallocatechin-3-gallate (EGCG), the main polyphenol found in green tea and putative DYRK1A inhibitor, improved some skeletal deficits. Because EGCG treatment improved mostly trabecular skeletal deficits, we hypothesized that increasing EGCG treatment dosage and length of administration would positively affect both trabecular and cortical bone in Ts65Dn mice. Treatment of individuals with DS with green tea extract (GTE) containing EGCG also showed some weight loss in individuals with DS, and we hypothesized that weights would be affected in Ts65Dn mice after EGCG treatment. Treatment with ~20 mg/kg/day EGCG for seven weeks showed no improvements in male Ts65Dn trabecular bone and only limited improvements in cortical measures. Comparing skeletal analyses after ~20mg/kg/day EGCG treatment with previously published treatments with ~9, 50, and 200 mg/kg/day EGCG showed that increased dosage and treatment time increased cortical structural deficits leading to weaker appendicular bones in male mice. Weight was not affected by treatment in mice, except for those given a high dose of EGCG by oral gavage. These data indicate that high doses of EGCG, similar to those reported in some treatment studies of DS and other disorders, may impair long bone structure and strength. Skeletal phenotypes should be monitored when high doses of EGCG are administered therapeutically.
Subject(s)
Catechin/analogs & derivatives , Down Syndrome/drug therapy , Muscle, Skeletal/drug effects , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , Animals , Catechin/administration & dosage , Catechin/adverse effects , Catechin/therapeutic use , Down Syndrome/metabolism , Drug Administration Schedule , Female , Male , Mice , Muscle, Skeletal/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Dyrk KinasesABSTRACT
(-)-Epigallocatechin gallate (EGCG) and tuna oil (TO) are beneficial bioactive compounds. EGCG, TO or a combination of, delivered by broccoli by-products (BBP), were added to an in vitro anaerobic fermentation system containing human fecal inocula to examine their ability to generate short-chain fatty acids (SCFA), metabolize EGCG and change the gut microbiota population (assessed by 16 S gene sequencing). Following 24 h fermentation, EGCG was hydrolyzed to (-)-epigallocatechin and gallic acid. EGCG significantly inhibited the production of SCFA (p < 0.05). Total SCFA in facal slurries with BBP or TO-BBP (48-49 µmol/mL) were significantly higher (p < 0.05) than the negative control with cellulose (21 µmol/mL). EGCG-BBP and TO-EGCG-BBP treatment increased the relative abundance of Gluconacetobacter, Klebsiella and Trabulsiella. BBP and TO-BBP showed the greatest potential for improving gut health with the growth promotion of high butyrate producers, including Collinsella aerofaciens, Bacillus coagulans and Lactobacillus reuteri.