Metabolome and Microbiome Analysis to Study the Flavor of Summer Black Tea Improved by Stuck Fermentation.

Tea is the most popular and widely consumed beverage worldwide, especially black tea. Summer tea has a bitter and astringent taste and low aroma compared to spring tea due to the higher content of polyphenols and lower content of amino acids. Microbial fermentation is routinely used to improve the flavor of various foods. This study analyzed the relationship between the quality of black tea, metabolic characteristics, and microbial communities after microbial stuck fermentation in summer black tea. Stuck fermentation decreased the bitterness, astringency sourness, and freshness, and increased the sweetness, mellowness, and smoothness of summer black tea. The aroma also changed from sweet and floral to fungal, with a significant improvement in overall quality. Metabolomics analysis revealed significant changes in 551 non-volatile and 345 volatile metabolites after fermentation. The contents of compounds with bitter and astringent taste were decreased. Sweet flavor saccharides and aromatic lipids, and acetophenone and isophorone that impart fungal aroma showed a marked increase. These changes are the result of microbial activities, especially the secretion of extracellular enzymes. Aspergillus, Pullululanibacillus, and Bacillus contribute to the reduction of bitterness and astringency in summer black teas after stuck fermentation, and Paenibacillus and Basidiomycota_gen_Incertae_sedis contribute positively to sweetness. In addition, Aspergillus was associated with the formation of fungal aroma. In summary, our research will provide a suitable method for the improvement of tea quality and utilization of summer tea, as well as provide a reference for innovation and improvement in the food industry.

Induction of Apoptosis via Inactivating PI3K/AKT Pathway in Colorectal Cancer Cells Using Aged Chinese Hakka Stir-Fried Green Tea Extract.

Food extract supplements, with high functional activity and low side effects, play a recognized role in the adjunctive therapy of human colorectal cancer. The present study reported a new functional beverage, which is a type of Chinese Hakka stir-fried green tea (HSGT) aged for several years. The extracts of the lyophilized powder of five HSGT samples with different aging periods were analyzed with high-performance liquid chromatography. The major components of the extract were found to include polyphenols, catechins, amino acids, catechins, gallic acid and caffeine. The tea extracts were also investigated for their therapeutic activity against human colorectal cancer cells, HT-29, an epithelial cell isolated from the primary tumor. The effect of different aging time of the tea on the anticancer potency was compared. Our results showed that, at the cellular level, all the extracts of the aged teas significantly inhibited the proliferation of HT-29 in a concentration-dependent manner. In particular, two samples prepared in 2015 (15Y, aged for 6 years) and 2019 (19Y, aged for 2 years) exhibited the highest inhibition rate for 48 h treatment (cell viability was 50% at 0.2 mg/mL). Further, all the aged tea extracts examined were able to enhance the apoptosis of HT-29 cells (apoptosis rate > 25%) and block the transition of G1/S phase (cell-cycle distribution (CSD) from <20% to >30%) population to G2/M phase (CSD from nearly 30% to nearly 10%) at 0.2 mg/mL for 24 h or 48 h. Western blotting results also showed that the tea extracts inhibited cyclin-dependent kinases 2/4 (CDK2, CDK4) and CylinB1 protein expression, as well as increased poly ADP-ribose polymerase (PRAP) expression and Bcl2-associated X (Bax)/B-cell lymphoma-2 (Bcl2) ratio. In addition, an upstream signal of one of the above proteins, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling, was found to be involved in the regulation, as evidenced by the inhibition of phosphorylated PI3K and AKT by the extracts of the aged tea. Therefore, our study reveals that traditional Chinese aged tea (HSGT) may inhibit colon cancer cell proliferation, cell-cycle progression and promoted apoptosis of colon cancer cells by inactivating PI3K/AKT signalling.

Quercetin-ferrum nanoparticles enhance photothermal therapy by modulating the tumor immunosuppressive microenvironment.

Photothermal therapy (PTT) was reported to induce synergistic immunogenic cell death (ICD) which may convert tumor cells into "therapeutic vaccines". However, this is often insufficient to prevent tumor recurrence, in part because of the immunosuppressive microenvironment in tumors. Therefore, remodeling tumor microenvironment is of great importance to enhance the therapeutic efficacy of PTT. We herein fabricated a versatile nano-photosensitizer by assembling quercetin and Ferrum ion (QFN). The released quercetin from QFN could reduce programmed death ligand 1 (PD-L1) in tumor cells by inhibiting the phosphorylation of JAK2 and STAT3, and reshape extracellular matrix (ECM) by down-regulating α-SMA+ fibroblast in tumors. Moreover, QFN could capture tumor antigen and deliver it to the tumor-draining lymph nodes after PTT, which further enhanced the activation of antigen-presenting cells. As a result, QFN-based PTT eliminated melanoma and induced long-term immune memory to prevent tumor metastasis and recurrence. This study provides an effective and translationally feasible photothermic agent for photothermal/immunotherapy. STATEMENT OF SIGNIFICANCE: The efficacy of photothermal therapy (PTT) in cancer treatment is often limited by the immunosuppressive microenvironment in tumors. Herein, we prepared a versatile photosensitizer by assembling quercetin and Ferrum ion (QFN). Upon near-infrared light irradiation, QFN-PTT induced cancer cells destruction and tumor antigen release. QFN then captured antigen and delivered it to the tumor-draining lymph nodes, thus promoting dendritic cell maturation and T cells activation. Quercetin released from QFN in tumors improved T cells infiltration and activation in tumor by regulating immunosuppressive microenvironment. The QFN-PTT-treated mice exhibited significantly elongated survival time, and gained strong anti-tumor immune memory to prevent tumor metastasis and recurrence. Thus, this work provided a simple and versatile photothermic agent, and it has important implications for designing effective and translationally feasible photosensitizers for PTT.

Tea and Citrus maxima complex induces apoptosis of human liver cancer cells via PI3K/AKT/mTOR pathway in vitro.

Objective: In this study, black tea and Citrus maxima (BT-CM), yellow tea and C. maxima (YT-CM), green tea and C. maxima (GT-CM) as subjects, the active ingredient content and antioxidant activity of three tea and C. maxima (T-CM) were analyzed. The effects of three T-CMs on apoptosis of liver cells in vitro and its mechanism were further explored. Methods: National standard method and HPLC were used for active ingredient analysis. MTT, cell flow cytometry and Western blot were used to analyze the effects of three T-CMs on cell proliferation, apoptosis, and its underlying molecular mechanism. Results: The content of tea polyphenols, free amino acids, ratio of polyphenols and amino acids, ester catechins, non-ester catechins and caffeine in YT-CM and GT-CM was significantly higher than that of BT-CM. The in vitro antioxidant capacity of YT-CM and GT-CM was also significantly stronger than that of BT-CM. Three T-CMs had the effects of inhibiting proliferation, arresting cell cycle and inducing apoptosis in HepG2 and Bel7402 cells, especially YT-CM and GT-CM. Western blot analysis showed three T-CMs activated PI3K/AKT/mTOR signaling pathway and regulated the expression levels of apoptosis-related proteins Bax, Bcl-2 and Caspase-3/9. YT-CM and GT-CM had better ability to change the signal pathway than BT-CM. Conclusion: In short, T-CMs, which combined different degrees of fermentation tea with C. maxima, were rich in nutrients and biologically active substances. T-CMs, especially YT-CM and GT-CM, are healthy drinks that help to prevent and treat liver cancer.

Shibi Tea (Adinandra nitida) and Camellianin A Alleviate CCl4-Induced Liver Injury in C57BL-6J Mice by Attenuation of Oxidative Stress, Inflammation, and Apoptosis.

Liver injury is a significant public health issue nowadays. Shibi tea is a non-Camellia tea prepared from the dried leaves of Adinandra nitida, one of the plants with the greatest flavonoid concentration, with Camellianin A (CA) being the major flavonoid. Shibi tea is extensively used in food and medicine and has been found to provide a variety of health advantages. The benefits of Shibi tea and CA in preventing liver injury have not yet been investigated. The aim of this study was to investigate the hepatoprotective effects of extract of Shibi tea (EST) and CA in mice with carbon tetrachloride (CCl4)-induced acute liver injury. Two different concentrations of EST and CA were given to model mice by gavage for 3 days. Treatment with two concentrations of EST and CA reduced the CCl4-induced elevation of the liver index, liver histopathological injury score, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Western blotting and immunohistochemical analysis demonstrated that EST and CA regulated the oxidative stress signaling pathway protein levels of nuclear factor E2-related factor 2 (Nrf2)/heme-oxygenase-1 (HO-1), the expression of inflammatory cytokines, the phosphorylated nuclear factor-kappaB p65 (p-NF-κB)/nuclear factor-kappaB p65 (NF-κB) ratio, the phospho-p44/42 mitogen-activated protein kinase (p-MAPK), and the apoptosis-related protein levels of BCL2-associated X (Bax)/B cell leukemia/lymphoma 2 (Bcl2) in the liver. Taken together, EST and CA can protect against CCl4-induced liver injury by exerting antioxidative stress, anti-inflammation, and anti-apoptosis.

Tea and its components reduce the production of uric acid by inhibiting xanthine oxidase.

Background: The health benefits of tea are as diverse including the reduction of uric acid levels. Xanthine oxidase is the most directly mediated enzyme in the production of uric acid. Objective: To explore the inhibitory effects of different teas and its main bioactive components on the production of uric acid. Design: Experimental study. The experiments were conducted in vitro using human immortalized normal liver cell line HL-7702 (L-02). Results: The inhibition of the xanthine oxidase activities and the expression level of xanthine dehydrogenase mRNA stimulated in the hyperuric hepatocyte cell model showed that the unfermented green tea and th1e lightly fermented yellow tea, white tea, and oolong tea significantly stronger than the highly fermented black tea and dark tea. The main bioactive compound, gallic acid, showed the strongest inhibitory effect on uric acid production, followed by tea polyphenols and theaflavins. Discussion: All teas exhibited significant inhibition of xanthine oxidase activities, and the degree of fermentation of tea may be inversely proportional to its ability to inhibit the production of uric acid. Compared with tea polyphenols rich in tea, gallic acid may be a more potential uric acid-lowering component. Conclusion: In this article, we first compared the effects of six traditional Chinese tea made from a single variety in stabilizing the synthesis of uric acid and found that the lighter the fermentation, the greater the potential for inhibiting the production of uric acid. Furthermore, we analyzed the inhibitory effects of its main biochemical active ingredients and found that the inhibitory effects of polyphenols rich in lightly fermented tea were significantly stronger than caffeine rich in highly fermented tea. Our findings will be helpful for people to choose a proper tea for alleviating hyperuricemia and provide a scientific basis for uric acid-lowering tea processing.

Citrus maxima and tea regulate AMPK signaling pathway to retard the progress of nonalcoholic fatty liver disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disease that easily induces hepatitis, cirrhosis, and even liver cancer. The long-term use of NAFLD therapeutic drugs produces toxicity and drug resistance. Therefore, it is necessary to develop high efficiency and low-toxicity active ingredients to alleviate NAFLD. Objective: This study aimed to reveal the role and mechanism of a new functional food CMT in alleviating NAFLD. Results: In the ob/ob fatty liver mice models, the CMT extracts significantly inhibited the weight gain of the mice and reduced the accumulation of white fat. The anatomical and pathological results showed that CMT relieved fatty liver in mice and reduced excessive lipid deposition and inflammatory infiltration. Serological and liver biochemical indicators suggest that CMT reduced dyslipidemia and liver damage caused by fatty liver. CMT obviously activated the adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-coA carboxylase (ACC) and AMPK/fatty acid synthase (FAS) signaling pathways, promoted fat oxidation, and inhibited synthesis. Moreover, CMT regulated the expression of inflammatory factors to relieve hepatitis caused by NAFLD. Conclusion: The study explained the role and mechanism of CMT in alleviating NAFLD and suggested that the active ingredients of CMT might be beneficial in NAFLD therapy.

Extract of Jasminum grandiflorum L. alleviates CCl4-induced liver injury by decreasing inflammation, oxidative stress and hepatic CYP2E1 expression in mice.

Jasminum grandiflorum L. (JG) is a medicinal plant containing many bioactive ingredients. Herein, we analyzed the effects of four different extracts and two compounds of JG on acute liver injury caused by carbon tetrachloride (CCl4) and underlying molecular mechanisms. 7 weeks old C57BL/6 male mice were used to establish a liver injury model by injecting with 1% CCl4, 10 mL/kg ip. Four different extracts and two compounds of JG were given to mice by gavage for 3 days. Clinical and histological chemistry assays were performed to assess liver injury. Moreover, hepatic oxidative stress and inflammation related markers were determined by immunohistochemistry and western blotting. As a result, JG extracts and two functional components showed different degree of protect effects against CCl4-induced liver injury by the decrease of elevated serum transaminases and liver index, and the attenuation of histopathological changes in mice, among which JG extracted with petroleum ether (PET) had the most significant effect. In addition, PET remarkably alleviated hepatic oxidative stress and inflammation. Further studies revealed that PET significantly inhibited the TNF-α expression, signal pathway expression, NF-κB p65 and inflammatory factors IL-1ß and IL-6 expression in CCl4-induced liver injury mice. Nevertheless, hydroxytyrosol (HT) alleviated liver injury by reducing oxidative stress. Apart from PET extract, other extracts of JG can inhibit cytochrome CYP2E1 expression to protect liver tissue. These findings suggest that the extracts and its components of JG possesses the potential protective effects against CCl4-induced liver injury in mice by exerting antioxidative stress and anti-inflammation.

Aged green tea reduces high-fat diet-induced fat accumulation and inflammation via activating the AMP-activated protein kinase signaling pathway.

Background: Obesity is a global public health concern and increases the risk of metabolic syndrome and other diseases. The anti-obesity effects of various plant-derived bioactive compounds, such as tea extracts, are well-established. The mechanisms underlying the anti-obesity activity of Jinxuan green tea (JXGT) from different storage years are still unclear. Objective: The aim of this study was to evaluate the effects of JXGTs from three different years on the high fat diet (HFD)-fed mouse model. Design: The mice were divided into six groups, the control group received normal diet and the obese model group received HFD. We analyzed the effects of JXGTs from 2005, 2008, and 2016 on HFD-fed obese mice over a period of 7 weeks. Results: The JXGTs reduced the body weight of the obese mice, and also alleviated fat accumulation and hepatic steatosis. Mechanistically, JXGTs increased the phosphorylation of AMP-activated protein kinase (p-AMPK)/AMP-activated protein kinase (AMPK) ratio, up-regulated carnitine acyl transferase 1A (CPT-1A), and down-regulated fatty acid synthase (FAS), Glycogen synthase kinase-3beta (GSK-3ß), Peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1α), Interleukin 6 (IL-6), and Tumour necrosis factor alpha (TNFα). Thus, JXGTs can alleviate HFD-induced obesity by inhibiting lipid biosynthesis and inflammation, thereby promoting fatty acid oxidation via the AMPK pathway. Discussion: The anti-obesity effect of three aged JXGTs were similar. However, JXGT2016 exhibited a more potent activation of AMPK, and JXGT2005 and JXGT2008 exhibited a more potent inhibiting glycogen synthase and inflammation effect. Furthermore, the polyphenol (-)-epicatechin (EC) showed the strongest positive correlation with the anti-obesity effect of JXGT. Conclusions: These findings demonstrate that JXGT treatment has a potential protection on HFD-induced obesity mice via activating the AMPK/CPT-1A and down-regulating FAS/GSK-3ß/PGC-1α and IL-6/TNFα. Our study results also revealed that different storage time would not affect the anti-obesity and anti-inflammation effect of JXGT.

Chinese Tea Alleviates CCl4-Induced Liver Injury through the NF-κBorNrf2Signaling Pathway in C57BL-6J Mice.

Liver injury is a life-threatening condition that is usually caused by excessive alcohol consumption, improperdiet, and stressful lifestyle and can even progress to liver cancer. Tea is a popular beverage with proven health benefits and is known to exert a protective effect on the liver, intestines, and stomach. In this study, we analyzed the therapeutic effects of six kinds of tea on carbon tetrachloride (CCl4)-induced liver injury in a mouse model. The mice were injected with 10 mL/kg 5% CCl4 to induce liver injury and then given oral gavage of green tea, yellow tea, oolong tea, white tea, black tea, and dark tea, respectively. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and the expression levels of inflammation and oxidative stress-related proteins in the liver tissues were quantified. All six kinds of tea partly reduced the liver index, restored the size of the enlarged liver in the CCl4 model, and decreased the serum levels of ALT and AST. Furthermore, the highly fermented dark tea significantly reduced the expression levels of NF-κB and the downstream inflammatory factors, whereas the unfermented green tea inhibited oxidative stress by activating the antioxidant Nrf2 pathway. Taken together, tea can protect against liver inflammation, and unfermented tea can improve antioxidant levels. Further studies are needed on the bioactive components of tea to develop drugs against liver injury.

Green tea peptides ameliorate diabetic nephropathy by inhibiting the TGF-ß/Smad signaling pathway in mice.

Diabetic nephropathy (DN) is the most important cause of middle and late-stage chronic kidney disease. Green tea polypeptides are extracted from tea pomace, and exhibit various pharmacological effects. In this study, we analyzed the reno-protective effects of green tea peptides in diabetic db/db mice, and explored the underlying mechanisms. Peptide treatment for 5 weeks significantly reduced the blood glucose levels and other indices of diabetes, and alleviated renal injury measured in terms of blood creatinine, urea nitrogen and urinary albumin/urinary creatinine levels. Mechanistically, the green tea peptides downregulated p-Smad2/3, α-SMA, ZO-1 and vimentin proteins in the kidney tissues, and elevated Smad7. Thus, green tea peptides inhibited the deposition of ECM proteins by suppressing excessive activation of the TGF-ß/Smad signaling pathway and reducing fibronectin levels. On the other hand, tea peptides ameliorated renal injury by inhibiting the production of inflammatory factors (iNOS and TNF-α) by suppressing the NF-κB signaling pathway. In addition, we confirmed the inhibitory effect of green tea peptides on the TGF-ß/Smad signaling pathway in TGF-ß1-stimulated HK-2 cells. Therefore, tea peptides can be considered as an effective candidate for alleviating DN.

Theaflavin-3,3'-di-gallate represses prostate cancer by activating the PKCδ/aSMase signaling pathway through a 67 kDa laminin receptor.

Prostate cancer is a major cause of morbidity and mortality in men. Theaflavin-3,3'-digallate (TF-3) is an important functional ingredient of black tea. We aimed to evaluate the cytotoxic effects of TF-3 on prostate cancer and to identify the underlying molecular mechanism. In this study, we explored the effects of TF-3 on prostate cancer in PC-3 cells and in NOD/SCID mice with prostate cancer. The results demonstrated that TF-3 inhibited prostate cancer cell proliferation by regulating the PKCδ/aSMase signaling pathway. The anti-prostate cancer effect of TF-3 was attributed to the expression of the 67 kDa laminin receptor (67LR), which is overexpressed in various cancers, playing a vital role in the growth and metastasis of tumor cells. Stable knockdown of 67LR could efficiently inhibit TF-3 induced apoptosis and cell cycle arrest in PC-3 cells, through interacting with the PKCδ/aSMase signaling pathway. In vivo studies also confirmed the above findings that TF-3 effectively inhibited tumor growth in terms of tumor volume. TF-3 treatment can significantly inhibit tumor growth and up-regulate the phosphorylation of PKCδ and the expression of aSMase in tumor xenografts developed by subcutaneously implanting PC-3 cells and 67LR-overexpressing PC-3 cells in mice. However, in tumor xenografts formed by subcutaneously implanting 67LR-knockdown PC-3 cells, TF-3 has no significant effect on PKCδ/aSMase pathway regulation and tumor growth inhibition.

Gastroprotective effects of extract of Jasminum grandiflorum L. flower in HCl/EtOH-induced gastric mucosal ulceration mice.

Jasminum grandiflorum L. is a medicinal plant used to treat hepatitis and gastritis, but the mechanisms underlying its protective effects against gastrointestinal mucosal damage remain to be elucidated. In this study, we analyzed the effects of four different extracts and two compounds from the flower of J. grandiflorum in a mouse model of HCl/EtOH-induced gastric ulcer. The flower extracts alleviated gastric mucosal ulceration by increasing PGE2 production and the activity of antioxidant enzymes, along with the suppression of reactive oxygen species (ROS) generation, lipid peroxidation, apoptosis-related proteins, pro-inflammatory cytokines and nitric oxide (NO) production.

Preventative and Therapeutic Potential of Flavonoids in Peptic Ulcers.

Peptic ulcer disease is a common gastrointestinal tract disorder that affects up to 20% of the population of the world. Treatment of peptic ulcer remains challenging due to the limited effectiveness and severe side effects of the currently available drugs. Hence, natural compounds, owing to their medicinal, ecological, and other safe properties, are becoming popular potential candidates in preventing and treating peptic ulcers. Flavonoids, the most abundant polyphenols in plants, exhibit gastroprotective effects against peptic ulcer both in vivo and in vitro. In this review, we summarized the anti-ulcer functions and mechanisms, and also the bioavailability, efficacy, and safety, of flavonoid monomers in the gastrointestinal tract. Flavonoids exerted cytoprotective and rehabilitative effects by not only strengthening defense factors, such as mucus and prostaglandins, but also protecting against potentially harmful factors via their antioxidative, anti-inflammatory, and antibacterial activities. Although controlled clinical studies are limited at present, flavonoids have shown a promising preventable and therapeutic potential in peptic ulcers.

Mixtures of Tea and Citrus maxima (pomelo) Alleviate Lipid Deposition in HepG2 Cells Through the AMPK/ACC Signaling Pathway.

Tea and citrus maxima are natural, medicinal homologous plants, typically used for making beverages, which have anticancer, antiobesity, and antioxidation properties. Green tea, yellow tea, and black tea were combined with citrus maxima to obtain green tea and Citrus maxima (GTCM), yellow tea and Citrus maxima (YTCM), and black tea and Citrus maxima (BTCM). The biochemical components of these mixtures were analyzed, and their possible effects and mechanisms on relieving liver lipid deposition were explored. The tea polyphenols, free amino acids, phenolamine ratio, and caffeine were comparable in YTCM and GTCM, being significantly higher than those in BTCM. In addition, the content of esterified catechins, nonesterified catechins, and total catechins in YTCM was significantly higher than those in GTCM and BTCM. All three mixtures of Citrus maxima tea significantly reduced lipid deposition in HepG2 cells, with GTCM and YTCM being slightly more effective than BTCM. Regarding the possible mechanism, Western blot analysis revealed that the three Citrus maxima tea mixtures could activate the AMPK/ACC signaling pathway, upregulate the expression of p-AMPK, p-ACC, and CPT-1 proteins, and downregulate the expression of SREBP1c and fatty acid synthase proteins to inhibit fat synthesis, thereby relieving lipid deposition in liver cells. In conclusion, as a novel and healthy beverage, Citrus maxima tea has the potential to alleviate liver lipid deposition, and further could be responsible for obesity treatment.

Antiobesity and anti-inflammation effects of Hakka stir-fried tea of different storage years on high-fat diet-induced obese mice model via activating the AMPK/ACC/CPT1 pathway.

BACKGROUND: As a typical representative of metabolic syndrome, obesity is also one of the extremely dangerous factors of cardiovascular diseases. Thus, the prevention and treatment of obesity has gradually become a global campaign. There have been many reports that green tea is effective in preventing obesity, but as a kind of green tea with regional characteristics, there have been no reports that Hakka stir-fried tea (HT) of different storage years has a weight loss effect. AIMS: The aim was to investigate the effect of HT in diet-induced obese mice. METHODS: The mice were divided into five groups as follows: the control group received normal diet; the obese model group received high-fat diet; and HT2003, HT2008, and HT2015 groups, after the induction of obesity via a high-fat diet, received HT of different storage years treatment for 6 weeks, respectively. RESULTS: It was observed that HT decreased the levels of serum and liver triglyceride; the ratio of liver to body weight; accumulation of epididymal, perirenal, and mesenteric fat; the degree of hepatic steatosis; and adipocyte hypertrophy, with the concomitant reduction of body weight. Moreover, HT decreased the expression levels of proinflammatory cytokines tumor necrosis factor α (TNF α), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and reduced fatty acid synthase (FAS) activity in liver tissue of obese mice. In addition, HT treatment also increased the phosphorylation of AMP-activated protein kinase (AMPK) and its direct downstream proteins, acetyl coenzyme A carboxylase (ACC), and carnitine palmitoyltransferase I (CPT-1), which participate in FAS pathway. CONCLUSIONS: These findings demonstrate that HT treatment has a potential protection on high-fat diet-induced obesity mice via activating the AMPK/ACC/CPT1 pathway, and to a certain extent, it has nothing to do with the storage time of three kinds of HT.

Green Tea Polyphenol EGCG Attenuates MDSCs-mediated Immunosuppression through Canonical and Non-Canonical Pathways in a 4T1 Murine Breast Cancer Model.

Several studies in the past decades have reported anti-tumor activity of the bioactive compounds extracted from tea leaves, with a focus on the compound epigallocatechin-3-gallate (EGCG). However, further investigations are required to unravel the underlying mechanisms behind the anti-tumor activity of EGCG. In this study, we demonstrate that EGCG significantly inhibits the growth of 4T1 breast cancer cells in vitro and in vivo. EGCG ameliorated immunosuppression by significantly decreasing the accumulation of myeloid-derived suppressor cells (MDSCs) and increasing the proportions of CD4+ and CD8+ T cells in spleen and tumor sites in 4T1 breast tumor-bearing mice. Surprisingly, a low dose of EGCG (0.5-5 µg/mL) effectively reduced the cell viability and increased the apoptosis rate of MDSCs in vitro. EGCG down-regulated the canonical pathways in MDSCs, mainly through the Arg-1/iNOS/Nox2/NF-κB/STAT3 signaling pathway. Moreover, transcriptomic analysis suggested that EGCG also affected the non-canonical pathways in MDSCs, such as ECM-receptor interaction and focal adhesion. qRT-PCR further validated that EGCG restored nine key genes in MDSCs, including Cxcl3, Vcan, Col4a1, Col8a1, Oasl2, Mmp12, Met, Itsnl and Acot1. Our results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine breast tumor model.

Green tea and black tea inhibit proliferation and migration of HepG2 cells via the PI3K/Akt and MMPs signalling pathway.

BACKGROUND AND AIMS: Black tea and green tea were produced via different processing techniques from the same tea leave variety. Then, biochemical components of the two water extracts were analysed to study cell apoptosis, migration and invasion of HepG2 cells induced by black tea and green tea. METHOD: The monomer components of the black tea and green tea extracts were analysed by colorimetry and HPLC, with MTT assay and colony formation assays used to assess cell proliferation and viability. The effects of black tea and green tea on apoptosis of HepG2 cells were verified by flow cytometry, with wound healing and Transwell experiments used to detect cell invasion and metastasis. The expression of PI3K/Akt signalling and apoptosis-related proteins as well as epithelial-mesenchymal transition (EMT) regulatory factor in HepG2 cells were determined by western blotting after black tea and green tea treatment. RESULTS AND CONCLUSIONS: Black tea and green tea extracts demonstrated different degrees of inhibition of cell migration and invasion, with green tea inducing more HepG2 cell apoptosis. In addition, green tea and black tea extracts inhibited the growth of HepG2 cells and induced apoptosis via PI3K/Akt, and inhibited cell migration and invasion through the MMPs signalling pathway. This study revealed the effects of fermented (black tea) and non-fermented tea (green tea) on liver cancer cells, providing a basis for the investigation of tea extracts for their anti-tumour potential.

Theaflavin TF3 Relieves Hepatocyte Lipid Deposition through Activating an AMPK Signaling Pathway by targeting Plasma Kallikrein.

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the leading cause of chronic liver diseases throughout the world. The deficit of pharmacotherapy for NAFLD calls for an urgent need for a new drug discovery and lifestyle management. Black tea is the most popular and functional drink consumed worldwide. Its main bioactive constituent theaflavin helps to prevent obesity-a major risk factor for NAFLD. To find new targets for the development of effective and safe therapeutic drugs from natural plants for NAFLD, we found a theaflavin monomer theaflavin-3,3'-digallate (TF3), which significantly reduced lipid droplet accumulation in hepatocytes, and directly bound and inhibited the activation of plasma kallikrein (PK), which was further proved to stimulate adenosine monophosphate activated protein kinase (AMPK) and its downstream targets. Taken together, we proposed that the TF3-PK-AMPK regulatory axis is a novel mechanism of lipid deposition mitigation, and PK could be a new target for NAFLD treatment.

A combination of Citrus reticulata peel and black tea inhibits migration and invasion of liver cancer via PI3K/AKT and MMPs signaling pathway.

Liver cancer, one of the most common malignancies, is the second leading cause of cancer death in the world. The citrus reticulate peel and black tea have been studied for their beneficial health effects. In spite of the many studies have been reported, the underlying molecular mechanisms underlying its health benefits are still not fully understood. In present study, we developed a unique citrus reticulate peel black tea (CRPBT) by combined citrus reticulate peel and black tea and assessed its active ingredients, anti-oxidant and anti-liver cancer effects in vitro. The results suggested that CRPBT exhibited antioxidant capacity and effectively inhibited proliferation and migration of liver cancer cells in a dose- and time- dependent manner. Mechanistically, CRPBT significantly down-regulated phosphorylation of PI3K and AKT, and up-regulated the ratio of Bax/Bcl-2, and suppressed the expression of MMP2/9, N-cadherin and Vimetin proteins in liver cancer cells. Taken together, CRPBT has good effect on inhibiting migration, invasion, proliferation, and inducing apoptosis in liver cancer cells.