Green Tea Encourages Growth of Akkermansia muciniphila.

Trillions of microorganisms reside in the hosts' gut. Since diverse activities of gut microbiota affect the hosts' health status, maintenance of gut microbiota is important for maintaining human health. Green tea (GT) has multiple beneficial effects on energy metabolism with antiobesity, antidiabetic, and hypolipidemic properties. As GT contains a large amount of bioactive ingredients (e.g., catechins), which can be metabolized by microorganisms, it would be feasible that consumption of GT may cause compositional changes in gut microbiota, and that the changes in gut microbiota would be associated with the beneficial effects of GT. In this study, we demonstrated that consumption of GT extract relieves high-fat diet-induced metabolic abnormalities. Interestingly, GT administration significantly encouraged the growth of Akkermansia muciniphila (Akkermansia), a beneficial microorganism to relieve obesity and related metabolic disorders. Finally, we found that epigallocatechin gallate is the component of GT that stimulates the growth of Akkermansia. According to these data, we propose that GT could be a prebiotic agent for Akkermansia to treat metabolic syndromes.

Gallocatechin Gallate-Containing Fermented Green Tea Extract Ameliorates Obesity and Hypertriglyceridemia Through the Modulation of Lipid Metabolism in Adipocytes and Myocytes.

Green tea is reported to exert beneficial effects on metabolic disorders through the regulation of lipid metabolism. On the contrary, fermented food products have been introduced to improve human health by modulating immune response and energy metabolism. To maximize health benefit, we applied fermentation processing to green tea. Fermented green tea extract (FGT) inhibited adipogenesis and lipogenesis in cultured adipocytes, whereas it augmented mRNA expression of fatty acid oxidation-related genes in differentiated myocytes. In diet-induced obese mice, FGT blunted body weight and fat mass gain by 69.7% and 56.7%, respectively. FGT also improved circulating triglyceride concentrations by 32.6%. Similar to in vitro results, FGT suppressed lipogenesis and promoted lipid catabolism in peripheral tissues. In addition, FGT administration modulated the composition of certain gut microbiota which are associated with obesity and related metabolic disorders. Among the various components of FGT, gallocatechin gallate is suggested to mediate the effect of FGT on lipid metabolism. Taken together, we propose FGT as a novel functional food to benefit human health by controlling adiposity and lipid metabolism.

Green satsuma mandarin orange (Citrus unshiu) extract reduces adiposity and induces uncoupling protein expression in skeletal muscle of obese mice.

Increased fat mass, which is induced by the storage of excess nutrients, is considered a causal factor for various metabolic disorders, including insulin resistance, type 2 diabetes, hyperlipidemia, hyperglycemia, hypertension, atherosclerosis, and non-alcoholic fatty liver disease. Therefore, it is necessary to prevent hyperadiposity to sustain a healthy life. Recently, uncoupling proteins (UCPs) were suggested to be molecular targets for curing obesity and its complications. In this study, green satsuma mandarin orange (Citrus unshiu) extract (GME) increased UCP3 expression in cultured myocytes. In a diet-induced obese animal model, administration of GME reduced fat mass and average fat cell size. Similar to in vitro experiments, GME restored expression of UCP3 in skeletal muscle. Moreover, GME also induced UCP2 expression in skeletal muscle. In conclusion, GME is suggested to be a novel functional dietary supplement for adiposity control through induction of UCPs.

Quercetin and fisetin enhanced the small intestine cellular uptake and plasma levels of epi-catechins in in vitro and in vivo models.

Quercetin and fisetin, known as catechol-containing flavonoids, could positively affect the absorption of catechins due to their strong affinity for catechol-O-methyl transferase (COMT), which can methylate and cause the excretion of catechins. The current study examined the effect of quercetin and fisetin on the absorption of epi-catechins (ECs) by using a Caco-2 cell line and an in vivo model. The intestinal transport of total catechins by Caco-2 cells was enhanced from 1.3- to 1.6-fold and 1.4- to 1.7-fold by adding quercetin and fisetin, respectively, compared to the control. It was even higher in the treatment with a mixture of quercetin and fisetin. While EC had the highest value of intestinal transport (169% of the control) in 10% quercetin treatment, EGC (235%), EGCG (244%), and ECG (242%) were significantly transported in the treatment with a 5% mixture of quercetin and fisetin (p < 0.05). In an in vivo pharmacokinetic study, the values of the area under the plasma concentration-time curve (AUC, ng h mL-1) were also higher in rats orally administered EGCG with 10% quercetin (365.5 ± 25.5) or 10% fisetin (825.3 ± 46.7) than in those administered EGCG only (111.3 ± 13.1). Methylated quercetin and methylated fisetin were determined to be m/z 317.24 and m/z 301.25 [M + H]+ with their own product ions, respectively. The results indicate that quercetin or fisetin is superior to ECs for methylation by COMT.

Influence of flavonol-rich excipient food (onion peel and Dendropanax morbifera) on the bioavailability of green tea epicatechins in vitro and in vivo.

The impacts of onion peel (OP) and Dendropanax morbifera (DM), as excipient foods rich in flavonols, on the digestive recovery, intestinal absorption, and pharmacokinetics of GT epicatechins were studied via an in vitro digestion model system with Caco-2 cells and an in vivo study. The digestive stability of total epicatechins recovered from GT upon the addition of 2% DM was up to 1.12 times higher than that observed with OP. The combined effects of OP and DM, which were observed with 2% OP + DM in a ratio of 1 : 4 (w : w), significantly increased (by a factor of 1.31) the digestive recovery of total epicatechins (p < 0.05). Remarkable cellular uptakes of EC (185.36%) and ECG (188.08%) were found with 4% OP + DM (4 : 1, w : w), and those of EGC (112.30%) and EGCG (136.27%) were obtained with 2% OP + DM (4 : 1, w : w) and 1% OP + DM (1 : 1, w : w), respectively. The peak plasma concentrations of total epicatechins from GT, GT + 5% OP, GT + 5% DM, and GT + 2% OP + 2% DM were 1044.78 ± 609.10, 2267.18 ± 3734.38, 1270.35 ± 547.59, and 714.53 ± 499.27 ng mL-1, respectively. The Cmax value of total epicatechins in rats orally administrated with GT with 5% OP was found to be approximately twice of that obtained with GT alone. The co-ingestion of GT with flavonol-rich excipient foods possibly enhances the absorption of epicatechins because flavonols act as not only enhancers of digestive stability but also modulators of the biotransformation of epicatechins. The results obtained from the current study suggest that the absorption of GT catechins can vary depending upon the kinds and doses of excipient foods co-ingested.

Mass spectrometry-based metabolite profiling in the mouse liver following exposure to ultraviolet B radiation.

Although many studies have been performed on the effects of ultraviolet (UV) radiation on the skin, only a limited number of reports have investigated these effects on non-skin tissue. This study aimed to describe the metabolite changes in the liver of hairless mice following chronic exposure to UVB radiation. We did not observe significant macroscopic changes or alterations in hepatic cholesterol and triglyceride levels in the liver of UVB-irradiated mice, compared with those for normal mice. In this study, we detected hepatic metabolite changes by UVB exposure and identified several amino acids, fatty acids, nucleosides, carbohydrates, phospholipids, lysophospholipids, and taurine-conjugated cholic acids as candidate biomarkers in response to UVB radiation in the mouse liver by using various mass spectrometry (MS)-based metabolite profiling including ultra-performance liquid chromatography-quadrupole time-of-flight (TOF)-MS, gas chromatography-TOF-MS and nanomate LTQ-MS. Glutamine exhibited the most dramatic change with a 5-fold increase in quantity. The results from altering several types of metabolites suggest that chronic UVB irradiation may impact significantly on major hepatic metabolism processes, despite the fact that the liver is not directly exposed to UVB radiation. MS-based metabolomic approach for determining regulatory hepatic metabolites following UV irradiation will provide a better understanding of the relationship between internal organs and UV light.

Tea catechins and flavonoids from the leaves of Camellia sinensis inhibit yeast alcohol dehydrogenase.

Four new quercetin acylglycosides, designated camelliquercetisides A-D, quercetin 3-O-[α-L-arabinopyranosyl(1→3)][2-O″-(E)-p-coumaroyl][ß-D-glucopyranosyl(1→3)-α-L-rhamnopyranosyl(1→6)]-ß-D-glucoside (17), quercetin 3-O-[2-O″-(E)-p-coumaroyl][ß-D-glucopyranosyl(1→3)-α-L-rhamnopyranosyl(1→6)]-ß-D-glucoside (18), quercetin 3-O-[α-L-arabinopyranosyl(1→3)][2-O″-(E)-p-coumaroyl][α-L-rhamnopyranosyl(1→6)]-ß-d-glucoside (19), and quercetin 3-O-[2-O″-(E)-p-coumaroyl][α-L-rhamnopyranosyl(1→6)]-ß-D-glucoside (20), together with caffeine and known catechins, and flavonoids (1-16) were isolated from the leaves of Camellia sinensis. Their structures were determined by spectroscopic (1D and 2D NMR, IR, and HR-TOF-MS) and chemical methods. The catechins and flavonoidal glycosides exhibited yeast alcohol dehydrogenase (ADH) inhibitory activities in the range of IC(50) 8.0-70.3µM, and radical scavenging activities in the range of IC(50) 1.5-43.8 µM, measured by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical.

Tea triterpenoidal saponins from the roots of Camellia sinensis have inhibitory effects against alcohol dehydrogenase.

Ten new polyhydroxyolean-12-ene pentacyclic triterpenoidal saponins, named rogchaponins 1-10, were isolated from the methanolic extract of the roots of Camellia sinensis by a series of chromatographic methods (silica gel flash column and C18 MPLC followed by C18 HPLC). Their structures were established by 1D and 2D-NMR techniques along with IR and HR-TOF-MS. Rogchaponins R4 ( 4) and R5 (5) showed inhibitory activities against yeast alcohol dehydrogenase (ADH) with IC (50) values of 16.1 ± 3.2 and 15.4 ± 3.3 µM, respectively. A 4-methylpyrazole positive control exhibited an IC (50) of 2750 ± 50 µM. However, the saponins showed no inhibitory activity against yeast aldehyde dehydrogenase (ALDH).

Metabolomics analysis reveals the compositional differences of shade grown tea (Camellia sinensis L.).

The different cultivation methods affect tea quality by altering the basic metabolite profiles. In this study, the metabolome changes were investigated in green tea and shade cultured green tea (tencha) by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) coupled with a multivariate data set. The principal component analysis (PCA) and orthogonal projection to latent structures discriminate analysis (OPLS-DA) of green tea clearly showed higher levels of galloylquinic acid, epigallocatechin, epicatechin, succinic acid, and fructose, together with lower levels of gallocatechin, strictinin, apigenin glucosyl arabinoside, quercetin p-coumaroylglucosyl-rhamnosylgalactoside, kaempferol p-coumaroylglucosylrhamnosylgalactoside, malic acid, and pyroglutamic acid than tencha. The effects of some seasonal variations were also observed in the primary metabolite concentrations such as amino acids and organic acids. In addition, green tea showed stronger antioxidant activity than tencha in both April and July. The antioxidant activity of green tea samples were significantly correlated with their total phenol and total flavonoid contents. This present study delineates the possibility to get high umami and less astringent green teas in shade culture. It highlights the metabolomic approaches to find out the effect of cultivation methods on chemical composition in plants and the relationship with antioxidant activity.

Lithospermic acid derivatives from Lithospermum erythrorhizon increased expression of serine palmitoyltransferase in human HaCaT cells.

A MeOH extract of the dry root of Lithospermum erythrorhizon showed strong increasing effect on serine palmitoyltransferase (SPT) in normal human keratinocyte cells (HaCaT cells). Bioassay-guided separation on this extract using repeated chromatography resulted in the isolation of lithospermic acid (1) and two derivative esters, 9''-methyl lithospermate (2) and 9'-methyl lithospermate (3). Compounds 1-3 significantly increased SPT expressions in the relative quantity (%) of SPT1 mRNA as well as SPT2 mRNA. These constituents also raised the level of SPT protein in HaCaT cells in a dose-dependent manner, with the increased level of SPT protein in HaCaT cells of 55%, 23%, and 81% at the concentration of 100 microg/ml, respectively. This finding suggests that lithospermic acid and its derivatives from L. erythrorhizon might improve the permeability barrier by stimulating the protein level of SPT.