The modulatory effect of oolong tea polyphenols on intestinal flora and hypothalamus gene expression in a circadian rhythm disturbance mouse model

The interaction between host circadian rhythm and gut microbes through the gut-brain axis provides new clues for tea polyphenols to improve host health.Our present research showed that oolong tea polyphenols(OTP)improved the structural disorder of the intestinal flora caused by continuous darkness,thereby modulating the production of metabolites related to pyruvate metabolism,glycolysis/gluconeogenesis,and tryptophan metabolism to alleviate the steady-state imbalance.After fecal microbiota transplantation from the OTP group,the single-cell transcriptomic analysis revealed that OTP significantly increased the number of hypothalamus cell clusters,up-regulated the number of astrocytes and fibroblasts,and enhanced the expression of circadian rhythm genes Cry2,Per3,Bhlhe41,Nr1d1,Nr1d2,Dbp and Rorb in hypothalamic cells.Our results confirmed that OTP can actively improve the intestinal environmental state as well as internal/peripheral circadian rhythm disorders and cognitive impairment,with potential prebiotic functional characteristics to notably contribute to host health.

Antibacterial mechanism of kojic acid and tea polyphenols against Escherichia coli O157:H7 through transcriptomic analysis

Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in humans.The previous found that a combination of kojic acid and tea polyphenols exhibited better activity against E.coli O157:H7 than using either alone.This study aimed to explore responses underlying the antibacterial mechanisms of kojic acid and tea polyphenols from the gene level.The functional enrichment analysis by comparing kojic acid and tea polyphenols individually or synergistically against E.coli O157:H7 found that acid resistance systems in kojic acid were activated,and the cell membrane and genomic DNA were destructed in the cells,resulting in“oxygen starvation”.The oxidative stress response triggered by tea polyphenols inhibited both sulfur uptake and the synthesis of ATP,which affected the bacteria's life metabolic process.Interestingly,we found that kojic acid combined with tea polyphenols hindered the uptake of iron that played an essential role in the synthesis of DNA,respiration,tricarboxylic acid cycle.The results suggested that the iron uptake pathways may represent a novel approach for kojic acid and tea polyphenols synergistically against E.coli O157:H7 and provided a theoretical basis for bacterial pathogen control in the food industry.

Green tea polyphenols alleviate di-(2-ethylhexyl)phthalate-induced liver injury in mice

BACKGROUND Di(2-ethylhexyl)phthalate(DEHP)is a common plasticizer known to cause liver injury.Green tea is reported to exert therapeutic effects on heavy metal exposureinduced organ damage.However,limited studies have examined the therapeutic effects of green tea polyphenols(GTPs)on DEHP-induced liver damage.AIM To evaluate the molecular mechanism underlying the therapeutic effects of GTPs on DEHP-induced liver damage.METHODS C57BL/6J mice were divided into the following five groups:Control,model[DEHP(1500 mg/kg bodyweight)],treatment[DEHP(1500 mg/kg bodyweight)+GTP(70 mg/kg bodyweight),oil,and GTP(70 mg/kg bodyweight)]groups.After 8 wk,the liver function,blood lipid profile,and liver histopathology were examined.Differentially expressed micro RNAs(miRNAs)and mRNAs in the liver tissues were examined using high-throughput sequencing.Additionally,functional enrichment analysis and immune infiltration prediction were performed.The miRNA-mRNA regulatory axis was elucidated using the starBase database.Protein expression was evaluated using immunohistochemistry.RESULTS GTPs alleviated DHEP-induced liver dysfunction,blood lipid dysregulation,fatty liver disease,liver fibrosis,and mitochondrial and endoplasmic reticulum lesions in mice.The infiltration of macrophages,mast cells,and natural killer cells varied between the model and treatment groups.mmu-miR-141-3p(a differentially expressed miRNA),Zcchc24(a differentially expressed mRNA),and Zcchc24(a differentially expressed protein)constituted the miRNA-mRNA-protein regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage in mice.CONCLUSION This study demonstrated that GTPs mitigate DEHP-induced liver dysfunction,blood lipid dysregulation,fatty liver disease,and partial liver fibrosis,and regulate immune cell infiltration.Additionally,an important miRNAmRNA-protein molecular regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage was elucidated.

Plant-inspired biomimetic hybrid PVDF membrane co-deposited by tea polyphenols and 3-amino-propyl-triethoxysilane for high-efficiency oilin-water emulsion separation

Membrane pollution caused by separating oily wastewater is a big challenge for membrane separation technology.Recently,plant-/mussel-inspired interface chemistry has received more and more attention.Herein,a high antifouling poly(vinylidene fluoride)(PVDF)membrane,coated with tea polyphenols(TP,extracted from green tea)and 3-amino-propyl-triethoxysilane(APTES),was developed to purify oil-inwater emulsions.ATR-FTIR,XPS and SEM were used to demonstrate the evolution of surface biomimetic hybrid coatings.The performances of the developed membranes were investigated by pure water permeability and oil rejection for various surfactant-stabilized oil-in-water emulsions.The experimental results revealed that the membrane deposited with a mass ratio of 0.1/0.2 exhibited ultrahigh pure water permeability(14570 L·m^(-2)·h^(-1)·bar^(-1),1 bar=0.1 MPa)and isooctane-in-water emulsion permeability(5391 L·m^(-2)·h^(-1)·bar^(-1))with high separation efficiency(>98.9%).Even treated in harsh environment(acidic,alkaline and saline)for seven days,the membrane still maintained considerable underwater oleophobic property(148°–153°).The fabricated plant-inspired biomimetic hybrid membranes with excellent performances light a broad application prospect in the field of oily wastewater treatment.

Research Progress on the Therapeutic Mechanism of Tea Polyphenols in Neurodegenerative Diseases

In recent years, the incidence of neurodegenerative diseases, mainly Alzheimer’s disease, Parkinson’s disease, vascular dementia, and cerebral ischemia, has been rising gradually, which has a serious impact on the physiological state and quality of life of human beings in old age, and the current clinical drugs are unsatisfactory in terms of therapeutic efficacy and healing, which has made this kind of diseases become a social medical problem. Tea polyphenols are the main functional components of tea and have great potential in neuroprotection. In this paper, we review the research on tea polyphenols in neurodegenerative diseases, with the aim of providing a new entry point for the treatment of neurodegenerative diseases.

A review of pharmacological activity and application potential in food of tea polyphenols

Tea polyphenols(TP)is a class of polyhydroxy compounds isolated from tea.Modern biological and medical studies have shown that TP has many pharmacological activities,such as anti-inflammatory,anti-virus,anti-oxidation,anti-tumor and anti-radiation.Furthermore,these substances can be used as a potential drug component to positively guide the occurrence and development of certain diseases.Furthermore,because of the activities of TP,such as anti-oxidation and anti-bacteria,it can be applied in food preservation,color preservation,deodorization,and treatment of food processing by-products.Based on the research progress of TP in recent years,this paper summarizes the pharmacological activities of TP and expounds on its application potential in the field of food.In order to provide a theoretical reference for the research,development and utilization of TP.

Preparation and Drug-Release Property of Polycaprolactone (PCL)/Polyglycolic Acid (PGA) Composite Masterbatch with Drug of Tea Polyphenols (TPs)

In order to effectively control the drug-release rate of medical textiles,biodegradable polycaprolactone(PCL) and polyglycolic acid(PGA) were blended at various mass ratios to prepare composite masterbatches for medical textiles.The surface morphology and the chemical structure of the masterbatches were analyzed.The crystallization,mass losses,strengths and drug-release rates of the composite masterbatches at different PCL/PGA mass ratios were explored.The results show that the degradation rate of the PGA carrier is obvious higher than that of the PCL carrier,and PCL,PGA and the tea polyphenol(TP) drug just physically mix without chemical reaction.During the degradation,the strength of the composite masterbatches gradually decreases.In addition,the drug-release rates of composite masterbatches at different mass ratios are different,and the more the PGA in the composite masterbatches,the faster the drug release of the composite masterbatches.The drug-release rate of the composite masterbatches can be controlled by adjusting the contents of PCL and PGA.

Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats

AIM To investigate protective effects and molecular mechanisms of green tea polyphenols(GTP) on nonalcoholic fatty liver disease(NAFLD) in Zucker fatty(ZF) rats.METHODS Male ZF rats were fed a high-fat diet(HFD) for 2 wk then treated with GTP(200 mg/kg) or saline(5 m L/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase(ALT) and aspartate aminotransferase(AST), inflammatory cytokines and hepatic triglyceride and liver histology. Immunoblotting was used to detect phosphorylation of AMP-activated protein kinase(AMPK) acetyl-Co A carboxylase(ACC), and sterol regulatory element-binding protein 1c(SREBP1c). RESULTS Genetically obese ZF rats on a HFD presented with metabolic features of hepatic pathological changes comparable to human with NAFLD. GTP intervention decreased weight gain(10.1%, P = 0.052) and significantly lowered visceral fat(31.0%, P < 0.01). Compared with ZF-controls, GTP treatment significantly reduced fasting serum insulin, glucose and lipids levels. Reduction in serum ALT and AST levels(both P < 0.01) were observed in GTP-treated ZF rats. GTP treatment also attenuated the elevated TNFα and IL-6 in the circulation. The increased hepatic TG accumulation and cytoplasmic lipid droplet were attenuated by GTP treatment, associated with significantly increased expression of AMPK-Thr172(P < 0.05) and phosphorylated ACC and SREBP1c(both P < 0.05), indicating diminished hepatic lipogenesis and triglycerides out flux from liver in GTP treated rats. CONCLUSION The protective effects of GTP against HFD-induced NAFLD in genetically obese ZF rats are positively correlated to reduction in hepatic lipogenesis through upregulating the AMPK pathway.

Green tea polyphenols inhibit testosterone production in rat Leydig cells

This study investigated the acute effects of green tea extract （GTE） and its polyphenol constituents, （-）-epigallocatechin-3-gallate （EGCG） and （-）-epicatechin （EC）, on basal and stimulated testosterone production by rat Leydig cells in vitro. Leydig cells purified in a Percoll gradient were incubated for 3 h with GTE, EGCG or EC and the testosterone precursor androstenedione, in the presence or absence of either protein kinase A （PKA） or protein kinase C （PKC） activators. The reversibility of the effect was studied by pretreating cells for 15 min with GTE or EGCG, allowing them to recover for 1 h and challenging them for 2 h with human chorionic gonadotropin （hCG）, luteinizing hormone releasing hormone （LHRH）, 22（R）-hydroxycholesterol or androstenedione. GTE and EGCG, but not EC, inhibited both basal and kinase-stimulated testosterone production. Under the pretreatment conditions, the inhibitory effect of the higher concentration of GTE/EGCG on hCG/LHRH-stimulated or 22（R）- hydroxycholesterol-induced testosterone production was maintained, whereas androstenedione-supported testosterone production returned to control levels. At the lower concentration of GTE/EGCG, the inhibitory effect of these polyphenols on 22（R）-hydroxycholesterol-supported testosterone production was reversed. The inhibitory effects of GTE may be explained by the action of its principal component, EGCG, and the presence of a gallate group in its structure seems important for its high efficacy in inhibiting testosterone production. The mechanisms underlying the effects of GTE and EGCG involve the inhibition of the PKA/PKC signalling pathways, as well as the inhibition of P450 side-chain cleavage enzyme and 17β-hydroxysteroid dehydrogenase function.

Green tea polyphenols protect spinal cord neurons against hydrogen peroxide-induced oxidative stress

Green tea polyphenols are strong antioxidants and can reduce free radical damage. To investigate their neuroprotective potential, we induced oxidative damage in spinal cord neurons using hydrogen peroxide, and applied different concentrations （50-200μg,/mL） of green tea polyphenol to the cell medium for 24 hours. Measurements of superoxide dismutase activity, malondialdehyde content, and expression of apoptosis-related genes and proteins revealed that green tea polyphenol effectively alleviated oxidative stress. Our results indicate that green tea polyphenols play a protective role in spinal cord neurons under oxidative stress.

Green Tea Polyphenols Alleviate Autophagy Inhibition Induced by High Glucose in Endothelial Cells

Bovine aortic endothelial cells（BAECs）were cultured with high glucose（33 mmol/L）,4 mg/L green tea polyphenols（GTPs）or 4 mg/L GTPs co-treatment with high glucose for 24 h in the presence or absence of Bafilomycin-A1（BAF）.We observed that high glucose increased the accumulation of LC3-II.Treatment with BAF did not further increase the accumulation of LC3-II.

Advances in Research of Green Tea Polyphenols in Drug Development

This paper elaborated the chemical components,biological metabolism,and progress in the field of drug development of green tea polyphenols,mainly in the prevention and treatment of cancer,neurodegenerative diseases,and diabetes.The potential anti-tumor activity of tea polyphenols can be achieved through intervening in various stages of tumor generation,development,and metastasis.However,the development of tea polyphenols as a therapeutic drug still faces many challenges,such as low bioavailability.Nanoparticle-based drug delivery systems have particular advantages over the simple tea polyphenols.Since there are emerging safety issues and potential local drug overdose effects,it is necessary to determine the actual dosage and pharmacological mechanism of the drug after encapsulating the nanoparticles.

Chemopreventive Effects of Black Tea Polyphenols in Mouse Skin Model of Carcinogenesis

In the present investigations, the antitumorigenic effect of black tea polyphenols (BTP) in twcrstage mouse skin model of carcinogenesis was studied. The animals were initiated with a single 'subcarcinogenic' topical dose (52 μg/200 μl acetone ) of 7, 12-dimethylbenzanthracene (DMBA). To evaluate the anti-tumour initiating activity, BTP was topically applied twice a week for three weeks prior to DMBA application, followed by topical treatment with 12-o-tetradecanoyl phorbol-13-acetate (TPA) (5 μg/200 μl acetone, 2x/wk. ) as promoter. For evaluation of antitumor promoting activity, BTP was applied prior to each treatment of TPA. BTP application showed marked inhibitory effect as antitumour initiator as well as antitumour promoter in mouse skin medel of two-stage carcinogenesis. Since initiation involves genetic pathway and tumour promotion involves epigenetic pathway, it seems that BTP exerts its antitumorigenic effect by altering both genetic and epigenetic pathways

Allograft pretreatment for the repair of sciatic nerve defects: green tea polyphenols versus radiation

Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can elimi- nate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, improve tissue preservation, and minimize postoperative infection. In the present study, we investigate which intervention achieves better results. We produced a 1.0 cm sciatic nerve defect in rats, and divided the rats into four treatment groups： autograft, fresh nerve allograft, green tea polyphenol-pretreated （1 mg/mL, 4~C） nerve allograft, and irradiation-pre- treated nerve allograft （26.39 Gy/min for 12 hours; total 19 kGy）. The animals were observed, and sciatic nerve electrophysiology, histology, and transmission electron microscopy were carried out at 6 and 12 weeks after grafting. The circumference and structure of the transplanted nerve in rats that received autografts or green tea polyphenol-pretreated nerve allografts were similar to those of the host sciatic nerve. Compared with the groups that received fresh or irradiation-pre- treated nerve allografts, motor nerve conduction velocity in the autograft and fresh nerve allograft groups was greater, more neurites grew into the aUografts, Schwann cell proliferation was evident, and a large number of new blood vessels was observed; in addition, massive myelinated nerve fibers formed, and abundant microfilaments and microtubules were present in the axoplasm. Our findings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to trans- planting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation.

Counteraction of Nogo-A and axonal growth inhibitors by green tea polyphenols and other natural products

Neuronal injuries such as stroke,traumatic brain injury,and spinal cord injury are leading causes of major disability and death.Chronic therapy for these neuronal injuries requires the promotion of axonal regeneration from the remaining neurons（Schwab and Strittmatter,2014）.

Changes in Polyphenols and Antioxidant Activities of Yingshan Yunwu Tea during Digestion in Vitro

[Objectives]To explore the change rule of polyphenol content and antioxidant activity of coarse old leaves of Yingshan Yunwu Tea in the process of human digestion.[Methods]The coarse and old leaves of Yunwu tea in Yingshan,Huanggang,Hubei Province were selected as the research object,and their digestion in vitro was simulated.The total polyphenol content was determined by Folin-phenol reagent colorimetric method,and the DPPH radical scavenging activity and total antioxidant activity were determined.[Results]After simulated gastrointestinal digestion in vitro,the polyphenol content and antioxidant activity of coarse old leaf tea soup showed a downward trend.After gastrointestinal digestion,the polyphenol content in tea infusion separately decreased by 31.8%and 8.5%;the scavenging rate of DPPH free radical was 97%before digestion,decreased to 92%after gastric digestion and 65%after intestinal digestion,which decreased by 5%and 27%,respectively;after gastrointestinal digestion,the total antioxidant capacity of tea soup decreased by 4.7%and 3.1%,respectively.[Conclusions]This study provided a reference for the development and application of coarse old leaves of Yingshan Yunwu tea,and provided a reference for the nutritional value evaluation and comprehensive utilization of coarse old leaves,so as to make the best use of coarse tea leaves and reduce the waste of resources.

Green Tea Polyphenols Prevent Early Vascular Aging Induced by High-Fat Diet via Promoting Autophagy in Young Adult Rats

Objective Epidemiology studies indicate that green tea polyphenols(GTP)perform a protective effect on cardiovascular diseases,but the underlying mechanisms are complex.The present study aimed to investigate the effect of GTP on high-fat diets(HFD)induced-early vascular aging.Methods Six-week young adult Wistar rats were fed with standard chow or HFD in the presence and absence of GTP(200 mg/kg body weight)for 18 weeks.In vitro experiment,human umbilical vascular endothelial cells(HUVECs)were treated with palmitic acid(PA)and GTP.Results The results showed that GTP alleviated the disorganized arterial wall and the increased intima-media thickness induced by HFD.In addition,the vascular oxidative injury was suppressed following GTP treatment.Furthermore,GTP elevated the ratio of LC3-II/LC3-I and suppressed expression of p62/SQSTM1,and restored SIRT3 expression in the aorta of HFD rats.Consistently,in cultured HUVECs,GTP inhibited cell senescence indicated by SA-β-gal and promoted endothelial autophagy compared with the PA treatment group.The activity of SIRT3 was specifically inhibited by 3-TYP,and the protective effect of GTP was consequently abolished.Conclusion The findings indicated that GTP protected against early vascular senescence in young HFD rats via ameliorating oxidative injury and promoting autophagy which was partially regulated by the SIRT3 pathway.

Gene expression profiling of HepG_(2) cells after treatment with black tea polyphenols

This study aimed to determine the effects of black tea polyphenols on gene expression in hepatocellular cancer cells.The total RNA from HepG_(2) hepatocellular cancer cells treated with black tea polyphenols was subjected to Human 14K cDNA microarray analysis.Real-time PCR and Western blot analysis were conducted to verify microarray data.Black tea polyphenols treatment at the dose of 20 mg/L,40 mg/L or 80 mg/L for one to three days inhibited the growth of HepG_(2) cells in a dose and time dependent manner.A total of 48 genes showed more than two-fold change after black tea polyphenols treatment,including 17 upregulated genes and 31 downregulated genes,and they were involved in the regulation of cell growth,cell cycle,apoptosis,signaling,angiogenesis,tumor invasion and metastasis.Real-time PCR analysis of the selected genes showed that their mRNA expression changes were consistent with the microarray data.In addition,Western blot analysis of the selected genes showed that their protein expression changes were consistent with mRNA expression.In conclusion,gene expression profiles provide comprehensive molecular mechanisms by which black tea polyphenols exerts growth inhibition effects on cancer cells.The novel molecular targets identified in this study may be further exploited as therapeutic strategies for hepatocellular cancer.

ROS-related Enzyme Expressions in Endothelial Cells Regulated by Tea Polyphenols

Objective Elevation of reactive oxygen species (ROS), especially the level of superoxide is a key event in many forms of cardiovascular diseases. To study the mechanism of tea polyphenols against cardiovascular diseases, we observed the expressions of ROS-related enzymes in endothelial cells. Methods Tea polyphenols were co-incubated with bovine carotid artery endothelial cells (BCAECs) in vitro and intracellular NADPH oxidase subunits p22phox and p67phox, SOD-1, and catalase protein were detected using Western blot method. Results Tea polyphenols of 0.4 ug/mL and 4.0 ug/mL (from either green tea or black tea) down-regulated NADPH oxidase p22phox and p67phox expressions in a dose-negative manner (P<0.05), and up-regulated the expressions of catalase (P<0.05). Conclusions Tea polyphenols regulate the enzymes involved in ROS production and elimination in endothelial cells, and may be beneficial to the prevention of endothelial cell dysfunction and the development of cardiovascular diseases.

Antioxidant and anti-inflammatory roles of tea polyphenols in inflammatory bowel diseases

Polyphenols,including phenolic acids,flavonoids,and procyanidins,are abundant in food and beverage derived from plants.Tea(Camellia sinensis)is particularly rich in polyphenols(e.g.,catechins,theaflavins,thearubigins,gallic acid,and flavonols),which are thought to contribute to the health benefits of tea.High intake of tea polyphenols has been described to prevent and/or attenuate a variety of chronic pathological conditions like cardiovascular diseases,neurodegenerative diseases,diabetes,and cancer.This review focuses on established antioxidant and anti-inflammatory properties of tea polyphenols and underlying mechanisms of their involvement in inflammatory bowel diseases(IBD).Tea polyphenols act as efficient antioxidants by inducing an endogenous antioxidant defense system and maintaining intracellular redox homeostasis.Tea polyphenols also regulate signaling pathways such as nuclear factor-κB,activator protein 1,signal transducer and activator of transcriptions,and nuclear factor E2-related factor 2,which are associated with IBD development.Accumulating pieces of evidence have indicated that tea polyphenols enhance epithelial barrier function and improve gut microbial dysbiosis,contributing to the management of inflammatory colitis.Therefore,this study suggests that supplementation of tea polyphenols could prevent inflammatory conditions and improve the outcome of patients with IBD.