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An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13 C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

More catechins are found in green tea than in any other type of tea, with its predominant production taking place in Asian nations. Consumption of green tea has been strongly correlated with a reduced risk of many diseases. This study introduces a new, efficient, and reliable method for extracting total catechins using ultra-high-performance liquid chromatography coupled with an ID-X-Orbitrap Mass spectrometer (UHPLC-IDX-Orbitrap-MS). The method was then applied to quantify the catechin content in green tea, yielding results comparable to previously published studies. Among the various sources of green tea analyzed, the lowest average catechin content was observed in Vietnam, Japan (2: Matcha), and Morocco, ranging between 346 and 322 mg/L. Conversely, the highest average catechin content (between 424 and 422 mg/L) was found in Sri Lanka and Japan (1: Sencha). For the remaining green tea extracts, the catechin levels ranged from 367 to 410 mg/L, exhibiting similar values. These findings demonstrate the high reproducibility of the proposed extraction procedure, with a relative standard deviation (RSD) error of less than 15% for the catechin standard. Additionally, the limit of detection for catechins was determined to be 1 ng mL-1. This study serves as a pilot investigation for extracting catechins from various green tea sources. Future research will focus on identifying all active compounds present. Furthermore, it is worth noting that this study aligns with the goals set forth in Saudi Vision 2030, which aims to diversify the country's economy and promote scientific advancements in various fields, including healthcare and agriculture.

Green deep eutectic solvents (DESs) are widely used to extract bioactive components from plant biomass; however, hydrophilic DES and bioactive component isolation methods have not been developed. In this study, we synthesized hydrophilic DES (CL-CA-DES) using citric acid and choline chloride. We combined this with environmentally friendly anion- and cation-exchange resin column chromatographic isolation methods. This approach extracted and isolated four polyphenolic compounds (catechins, epicatechins, procyanidin B1, and procyanidin B2) from raspberry root and efficiently recovered the hydrophilic DES. CL-CA-DES extracted significantly higher contents of catechin and procyanidin B2 from raspberry root compared to other solvents. It also extracted substantially higher contents of epicatechin compared to butyl alcohol, 70% ethanol, and water, but there was no significant difference when compared with acetone and ethyl acetate. Additionally, CL-CA-DES extracted significantly higher contents of procyanidin B1 compared to butyl alcohol, water, and ethyl acetate, with no significant difference when compared with 70% ethanol and acetone. The isolation efficiency of the bioactive components in the raspberry root extract by anion- and cation-exchange resin column chromatography was higher than that of the organic solvent extraction and precipitation generation methods, and the method was effective in recovering CL-CA-DES with a recovery rate higher than 60%. In conclusion, this study developed a new method for the efficient recovery of hydrophilic CL-CA-DES, which can be used for isolating polyphenolic compounds from raspberry root., (© 2024 Institute of Food Technologists.)

Theaflavin-3,3'-digallate (TF3) is the most important theaflavin monomer in black tea. TF3 was proved to reduce blood glucose level in mice and rats. However, the elaborate anti-diabetic mechanism was not well elucidated. In this work, human hepatoma G2 (HepG2) cells and zebrafish ( Danio rerio ) were used simultaneously to reveal anti-diabetic effect of TF3. The results showed that TF3 could effectively rise glucose absorption capacity in insulin-resistant HepG2 cells and regulate glucose level in diabetic zebrafish. The hypoglycemic effect was mediated through down-regulating phosphoenolpyruvate carboxykinase and up-regulating glucokinase. More importantly, TF3 could significantly improve β cells regeneration in diabetic zebrafish at low concentrations (5 μg/mL and 10 μg/mL), which meant TF3 had a strong anti-diabetic effect. Obviously, this work provided the potential benefit of TF3 on hypoglycemic effect, regulating glucose metabolism enzymes, and protecting β cells. TF3 might be a promising agent for combating diabetes.

Methylxanthines and polyphenols from cocoa byproducts should be considered for their application in the development of functional ingredients for food, cosmetic and pharmaceutical formulations. Different cocoa byproducts were analyzed for their chemical contents, and skincare properties were measured by antioxidant assays and anti-skin aging activity. Musty cocoa beans (MC) and second-quality cocoa beans (SQ) extracts showed the highest polyphenol contents and antioxidant capacities. In the collagenase and elastase inhibition study, the highest effect was observed for the SQ extract with 86 inhibition and 36% inhibition, respectively. Among cocoa byproducts, the contents of catechin and epicatechin were higher in the SQ extract, with 18.15 mg/100 g of sample and 229.8 mg/100 g of sample, respectively. Cocoa bean shells (BS) constitute the main byproduct due to their methylxanthine content (1085 mg of theobromine and 267 mg of caffeine/100 g of sample). Using BS, various influencing factors in the extraction process were investigated by response surface methodology (RSM), before scaling up separations. The extraction process developed under optimized conditions allows us to obtain almost 2 g/min and 0.2 g/min of total methylxanthines and epicatechin, respectively. In this way, this work contributes to the sustainability and valorization of the cocoa production chain.

Alpinia officinarum (AO) has been traditionally used in Asia as an herbal medicine to treat inflammatory and internal diseases. However, the therapeutic effect of AO on atopic dermatitis (AD) is unclear. Therefore, we examined whether Alpinia officinarum water extract (AOWex) affects AD in vivo and in vitro. Oral administration of AOWex to NC/Nga mice with Dermatophagoies farina extract (DfE)-induced AD-like symptoms significantly reduced the severity of clinical dermatitis, epidermal thickness, and mast cell infiltration into the skin and ear tissue. Decreased total serum IgE, macrophage-derived chemokine (MDC), and regulated on activation, normal T-cell expressed and secreted (RANTES) levels were observed in DfE-induced NC/Nga mice in the AOWex-treated group. These effects were confirmed in vitro using HaCaT cells. Treatment with AOWex inhibited the expression of proinflammatory chemokines such as MDC, RANTES, IP-10 and I-TAC in interferon-γ and tumor necrosis factor-α-stimulated HaCaT cells. The anti-inflammatory effects of AOWex were due to its inhibitory action on MAPK phosphorylation (ERK and JNK), NF-κB, and STAT1. Furthermore, galangin, protocatechuic acid, and epicatechin from AOWex were identified as candidate anti-AD compounds. These results suggest that AOWex exerts therapeutic effects against AD by alleviating AD-like skin lesions, suppressing inflammatory mediators, and inhibiting major signaling molecules., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In this study heat-assisted extraction conditions were optimized to enhance extraction yield of antioxidant polyphenols from leaves of Himalayan Quercus species. In initial experiments, a five-factor Plackett-Burman design including 12 experimental runs was tested against the total polyphenolic content (TP). Amongst, XA: extraction temperature, XC: solvent concentration and XE: sample-to-solvent ratio had shown significant influence on yield. These influential factors were further subject to a three-factor-three-level Box-Wilson Central Composite Design; including 20 experimental runs and 3D response surface methodology plots were used to determine optimum conditions [i.e. XA: (80°C), XC:(87%), XE: (1g/40ml)].This optimized condition was further used in other Quercus species of western Himalaya, India. The High-Performance Liquid Chromatography (HPLC) revealed occurrence of 12 polyphenols in six screened Quercus species with the highest concentration of catechin followed by gallic acid. Amongest, Q. franchetii and Q. serrata shared maximum numbers of polyphenolic antioxidants (8 in each). This optimized extraction condition of Quercus species can be utilized for precise quantification of polyphenols and their use in pharmaceutical industries as a potential substitute of synthetic polyphenols., Competing Interests: The authors have declared that no competing interests exist.

Keratinocytes are rich in lipids and are the main sensitive cells to ultraviolet (UV) rays. Theaflavins are the core functional components of black tea and are known as the "soft gold" in tea. In this study, ultraviolet-B (UVB) irradiation caused apoptosis and necrosis of human epidermal keratinocytes (HaCaT). EGCG and the four theaflavins had anti-UVB damage activity, among which theaflavin-3'-gallate (TF3'G) had the best activity. The results of biophysical and molecular biology experiments showed that TF3'G has anti-damage effects on UVB-irradiated HaCaT cells through the dual effects of photoprotection and maintenance of cell homeostasis. That is, TF3'G preincubation could absorb UV rays, reduce the accumulation of aging-related heterochromatin (SAHF) formation, increase mitochondrial membrane potential, downregulate NF-κB inflammation pathways, inhibit the formation of cytotoxic aggregates, and protect biological macromolecules Structure, etc. The accumulation of conjugated π bonds and the balance benzoquinone are the core functional structure of TF3'G with high efficiency and low toxicity. The study indicates that TF3'G has the potential to inhibit the photoaging and intrinsic aging of skin cells., (Copyright © 2021. Published by Elsevier B.V.)

Cinnamon procyanidin oligomers (CPOs) are water-soluble components extracted from cinnamon. This study aims to explore the neuroprotection of B-type CPO (CPO-B) against 1-methyl-4-phenylpyridinium (MPP + )-mediated cytotoxicity and the molecular mechanisms underlying its protection. The results demonstrated that CPO-B showed protection by increasing cell viability, attenuating an intracellular level of reactive oxygen species, downregulating cleaved caspase-3 expression, and upregulating the Bcl-2/Bax ratio. Moreover, CPO-B completely blocked the dephosphorylation of extracellular, signal-regulated kinase 1 and 2 (Erk1/2) caused by MPP + . Treatment with an Erk1/2 inhibitor, SCH772984, significantly abolished the neuroprotection of CPO-B against MPP + . Taken together, we demonstrate that CPO-B from cinnamon bark provided protection against MPP + in cultured SH-SY5Y cells, and the potential mechanisms may be attributed to its ability to modulate the dysregulation between pro-apoptotic and anti-apoptotic proteins through the Erk1/2 signaling pathway. Our findings suggest that the addition of cinnamon to food or supplements might benefit patients with PD.

In the work, the effect of black tea on oxidative stress induced in the aorta by irradiation was studied. The efficiency of black and green tea types was compared, and the effect of the main green tea components (-)-epigallocatechin galate (EGCG) and (-)-epigallocatechin (EGC) on the aorta was studied. The activity of ACE in rat aorta segments was determined by measuring the hydrolysis of hippuryl-L-histidyl-L-leucine, and the production of ROS was estimated from the oxidation of dichlorodihydrofluorescein. Black tea prevented the radiation-induced activation of the ACE and suppressed increased ROS production in the aorta of irradiated rats. The IC 50 value for the suppression of the irradiation-induced increase in ACE activity is 1 ml of black tea brewed at a rate of 0.17 g/100 ml. Black tea is 12 times more effective than green tea. The administration of both catechin derivatives from green tea to rats leads to an increase in the activity of ACE and the formation of ROS in the aorta. The dose that provided half maximum activation of ACE (EC 50 ) on intraperitoneal (i. p.) injection of galloylated catechins was found to be the same, 0.06-0.07 μg/kg of body weight. Upon intragastric gavage of EGCG, the EC 50 value was by one order of magnitude higher, 0.8 μg/kg. Black tea was more effective than green tea in prevention a radiation-induced increase of ACE activity and oxidative stress in the aorta. This difference was explained by a low content of galloylated catechins in black tea., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Trichilia catigua is a tree known as "catuaba", widely distributed in Brazil. Studies carried out with T. catigua barks suggest that plant has antidepressant, antidiabetic, antimicrobial, antioxidant, antiviral, and preventive against brain damage. The aim of this work was to isolate and characterise compounds from the semipurified fraction of T. catigua barks, and to conduct microbiological screening against bacteria and fungi. The crude extract (CE) of "catuaba" was produced by turbo extraction with acetone-water, and later, partitioned to yield ethyl-acetate (EAF) and aqueous (AqF) fractions. From AqF the new catechin-3- O -α-L-rhamnoside-(4α→8)-epicatechin was isolated, identified, and described here for the first time. Regarding antimicrobial activity, the extracts presented impressive results, mainly for Vancomycin Resistant Enterococcus faecium (VRE fm ) with MIC of 156.5 μg/mL. The results suggest that extract of T. catigua could potentially be used as an adjuvant to treatment and is a promising candidate for the development of new antimicrobial drugs.

Background: Caulerpa lentillifera (CL) is a green seaweed, and its edible part represents added value as a functional ingredient. CL was dried and extracted for the determination of its active compounds and the evaluation of its biological activities. The major constituents of CL extract (CLE), including tannic acid, catechin, rutin, and isoquercetin, exhibited beneficial effects, such as antioxidant activity, anti-diabetic activity, immunomodulatory effects, and anti-cancer activities in in vitro and in vivo models. Whether CLE has an anti-inflammatory effect and immune response remains unclear., Methods: This study examined the effect of CLE on the inflammatory status and immune response of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the mechanisms involved therein. RAW264.7 cells were treated with different concentrations of CLE (0.1-1000 µg/mL) with or without LPS (1 µg/mL) for 24 h. Expression and production of the inflammatory cytokines, enzymes, and mediators were evaluated., Results: CLE suppressed expression and production of the pro-inflammatory cytokines IL-6 and TNF-α. Moreover, CLE inhibited expression and secretion of the inflammatory enzyme COX-2 and the mediators PGE2 and NO. CLE also reduced DNA damage. Furthermore, CLE stimulated the immune response by modulating the cell cycle regulators p27, p53, cyclin D2, and cyclin E2., Conclusions: CLE inhibits inflammatory responses in LPS-activated macrophages by downregulating inflammatory cytokines and mediators. Furthermore, CLE has an immunomodulatory effect by modulating cell cycle regulators.

Nutritional biomarkers are critical tools to objectively assess intake of nutrients and other compounds from the diet. In this context, it is essential that suitable analytical methods are available for the accurate quantification of biomarkers in large scale studies. Recently, structurally-related (-)-epicatechin metabolites (SREMs) and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone metabolites (gVLMs) were identified as biomarkers of intake of flavanols and procyanidins, a group of polyphenol bioactives. This study aimed at validating a high throughput method for the quantification of SREMs and gVLMs in plasma along with methylxanthines (MXs), dietary compounds known to interact with flavanol and procyanidin effects. To accomplish this, a full set of authentic analytical standards were used to optimize a micro solid phase extraction method for sample preparation coupled to HPLC-MS detection. Isotopically-labelled standards for all analytes were included to correct potential matrix effects on quantification. Average accuracies of 101%, 93% and 103% were obtained, respectively, for SREMs, gVLMs and MXs. Intra- and inter-day repeatability values were <15%. The method showed linear responses for all analytes (>0.993). Most SREMs and gVLMs had limits of quantifications <5 nM while limits of quantification of MXs were 0.2 μM. All analytes were stable under different tested processing conditions. Finally, the method proved to be suitable to assess SREMs, gVLMs and MXs in plasma collected after single acute and daily intake of cocoa-derived test materials. Overall, this method proved to be a valid analytical tool for high throughput quantification of flavanol and procyanidin biomarkers and methylxanthines in plasma.

The article reports the chemical composition, antioxidant, six key enzymes inhibitory and antimicrobial activities of two solvent extracts (water and methanol) of leaves and stem bark of Uapaca togoensis. For chemical composition, methanol extract of stem bark exhibited significant higher total phenolic (129.86 mg GAE/g) and flavanol (10.44 mg CE/g) contents. Methanol extract of leaves and water extract of stem bark showed high flavonoids (20.94 mg RE/g) and phenolic acid (90.40 mg CAE/g) content, respectively. In addition, HPLC-ESI-TOF-MS analysis revealed that U. togoensis was rich in procyanidins. The methanol and water extracts of stem bark had overall superior antioxidant activity; however, only methanol extract of stem bark showed higher inhibition of cholinesterase (AChE: 2.57 mg GALAE/g; BChE: 4.69 mg GALAE/g), tyrosinase (69.53 mg KAE/g) and elastase (2.73 mmol CE/g). Potent metal chelating ability was showed by water extract of leaves (18.94 mg EDTAE/g), higher inhibition of amylase was detected for water extracts of leaves (0.94 mmol ACAE/g) and stem bark (0.92 mmol ACAE/g). The tested extracts have shown wide-spectrum antibacterial properties and these effects have shown to be more effective against Aspergillus ochraceus, Penicillium funiculosum, Trichoderma viride, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The results revealed that the antioxidant, enzyme inhibitory and antimicrobial activities depended on the extraction solvents and the parts of plant. Bioinformatics analysis on the 17 major compounds showed modulation of pathway associated with cancer. In brief, U. togoensis might be valuable as potential source of natural agents for therapeutic application., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Although Australia is the largest exporter of faba bean globally, there is limited information available on the levels of bioactive compounds found in current commercial faba bean varieties grown in this country. This study profiled the phenolic acid and flavonoid composition of 10 Australian faba bean varieties, grown at two different locations. Phenolic profiling by HPLC-DAD revealed the most abundant flavonoid to be catechin, followed by rutin. For the phenolic acids, syringic acid was found in high concentrations (72.4-122.5 mg/kg), while protocatechuic, vanillic, p -hydroxybenzoic, chlorogenic, p -coumaric, and trans-ferulic acid were all found in low concentrations. The content of most individual phenolics varied significantly with the variety, while some effect of the growing location was also observed. This information could be used by food processors and plant breeders to maximise the potential health benefits of Australian-grown faba bean.

The oil recovery from Alyanak apricot kernel was 36.65% in control (unroasted) and increased to 43.77% in microwave-roasted kernels. The total phenolic contents in extracts from apricot kernel were between 0.06 (oven-roasted) and 0.20 mg GAE/100 g (microwave-roasted) while the antioxidant activity varied between 2.55 (oven-roasted) and 19.34% (microwave-roasted). Gallic acid, 3,4-dihydroxybenzoic acid, (+)-catechin and 1,2-dihydroxybenzene were detected as the key phenolic constituents in apricot kernels. Gallic acid contents varied between 0.53 (control) and 1.10 mg/100 g (microwave-roasted) and 3,4-dihydroxybenzoic acid contents were between 0.10 (control) and 0.35 mg/100 g (microwave-roasted). Among apricot oil fatty acids, palmitic acid contents ranged from 4.38 (oven-roasted) to 4.76% (microwave-roasted); oleic acid contents were between 65.73% (oven-roasted) and 66.15% (control) and linoleic acid contents varied between 26.55 (control) and 27.12% (oven-roasted).

Plant polyphenols have beneficial antioxidant effects on human health; practices aimed at preserving their content in foods and/or reusing food by-products are encouraged. The impact of the traditional practice of the water curing procedure of chestnuts, which prevents insect/mould damage during storage, was studied to assess the release of polyphenols from the fruit. Metabolites extracted from pericarp and integument tissues or released in the medium from the water curing process were analyzed by matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray-quadrupole-time of flight-mass spectrometry (ESI-qTOF-MS). This identified: (i) condensed and hydrolyzable tannins made of (epi)catechin (procyanidins) and acid ellagic units in pericarp tissues; (ii) polyphenols made of gallocatechin and catechin units condensed with gallate (prodelphinidins) in integument counterparts; (iii) metabolites resembling those reported above in the wastewater from the chestnut curing process. Comparative experiments were also performed on aqueous media recovered from fruits treated with processes involving: (i) tap water; (ii) tap water containing an antifungal Lb. pentosus strain; (iii) wastewater from a previous curing treatment. These analyses indicated that the former treatment determines a 6-7-fold higher release of polyphenols in the curing water with respect to the other ones. This event has a negative impact on the luster of treated fruits but qualifies the corresponding wastes as a source of antioxidants. Such a phenomenon does not occur in wastewater from the other curing processes, where the release of polyphenols was reduced, thus preserving the chestnut's appearance. Polyphenol profiling measurements demonstrated that bacterial presence in water hampered the release of pericarp metabolites. This study provides a rationale to traditional processing practices on fruit appearance and qualifies the corresponding wastes as a source of bioactive compounds for other nutraceutical applications.

A viscous solution of low molecular weight chitosan (CH) at 5% w/v (10.2 kDa, 75 % deacetylated, 1451 cP at 25 °C) was associated with a microemulsion (ME) that undergoes a phase transition after water absorption in situ (≈28 % w/w), forming a more viscous liquid crystal, which was potentially evaluated as a topical vehicle. The ME was selected from a phase diagram, selecting a composition based on Tween® 80 (52 %), myristate isopropyl (28 %), and the aqueous phase (water and polyethylene glycol 400, 60:40 w/w) (20 %), which was after replaced by CH and herbal medicines (HM). HM are alternatives to treat candidiasis, and Stryphnodendron adstringens shell extract, characterized by molecular networking, and Melaleuca alternifolia Chell essential oil (46 % of terpinen-4-ol), showed in vitro activity against Candida albicans. Associating CH in ME improved the mechanical properties of the topical formulation, as adhesiveness, which is an advantageous feature for the topical treatment of vulvovaginal candidiasis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Amyloid plaques accumulated by the amyloid-β (Aβ) fibrillar aggregates are the major pathological hallmark of the Alzheimer's disease (AD). Inhibiting aggregation and disassembling preformed fibrils of Aβ by natural small molecules have developed into a promising therapeutic strategy for AD. Previous experiments reported that the green tea extract epigallocatechin-3-gallate (EGCG) can disrupt Aβ fibril and reduce Aβ cytotoxicity. The inhibitory ability of EGCG can also be affected by cellular membranes. Thus, it is essential to consider the membrane influences in the investigation of protofibril-disruptive capability of EGCG. Here, we performed multiple all-atom molecular dynamic simulations to investigate the effect of EGCG on the Aβ 42 protofibril in the presence of a mixed POPC/POPG (7:3) lipid bilayer and the underlying molecular mechanisms of action. Our simulations show that in the presence of membrane bilayers, EGCG has a preference to bind to the membrane, and this binding alters the binding modes between Aβ 42 protofibril and the lipid bilayer, leading to a reduced membrane thinning, indicative of a protective effect of EGCG on the membrane. And EGCG still displays a disruptive effect on Aβ 42 protofibril, albeit with a lesser extent of disruption than that in the membrane-free environment. EGCG destabilizes the two hydrophobic core regions (L17-F19-I31 and F4-L34-V36), and disrupts the intrachain K28-A42 salt bridges. Our results reveal that in the presence of lipid bilayers, EGCG plays a dual role in Aβ 42 protofibril disruption and membrane protection, suggesting that EGCG could be a potential effective drug candidate for the treatment of AD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The galloyl moiety is a specific structural feature which dictates, in part, the chemopreventive properties of diet-derived catechins. In ovarian cancer cells, galloylated catechins were recently demonstrated to target the transforming growth factor (TGF)-β-mediated control of the epithelial-mesenchymal transition process. The specific impact of the galloyl moiety on such signaling, however, remains poorly understood. Here, we questioned whether the sole galloyl moiety interacted with TGF-β-receptors to alter signal transduction and chemotactic migratory response in an ES-2 serous carcinoma-derived ovarian cancer cell model. In line with the LogP and LogS values of the tested molecules, we found that TGF-β-induced Smad-3 phosphorylation and cell migration were optimally inhibited, provided that the lateral aliphatic chain of the galloyl moiety reached 8-10 carbons. Functional inhibition of the TGF-β receptor (TGF-βR1) kinase activity was supported by surface plasmon resonance assays showing direct physical interaction between TGF-βR1 and the galloyl moiety. In silico molecular docking analysis predicted a model where galloylated catechins may bind TGF-βR1 within its adenosine triphosphate binding cleft in a site analogous to that of Galunisertib, a selective adenosine triphosphate-mimetic competitive inhibitor of TGF-βR1. In conclusion, our data suggest that the galloyl moiety of the diet-derived catechins provides specificity of action to galloylated catechins by positioning them within the kinase domain of the TGF-βR1 in order to antagonize TGF-β-mediated signaling that is required for ovarian cancer cell invasion and metastasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier Inc.)

Context: Oxidative imbalance-induced cognitive impairment is among the most urgent clinical concerns. Isoflurane has been demonstrated to impair cognitive function via an increase in oxidative stress. GSP has strong antioxidant capacities, suggesting potential cognitive benefits. Objective: This study investigates whether GSP pre-treatment can alleviate isoflurane-induced cognitive dysfunction in mice. Materials and methods: C57BL/6J mice were pre-treated with either GSP 25-100 mg/kg/d for seven days or GSP 100-400 mg/kg as a single dose before the 6 h isoflurane anaesthesia. Cognitive functioning was examined using the fear conditioning tests. The levels of SOD, p-NR2B and p-CREB in the hippocampus were also analysed. Results: Pre-treatment with either a dose of GSP 50 mg/kg/d for seven days or a single dose of GSP 200 mg/kg significantly increased the % freezing time in contextual tests on the 1st (72.18 ± 12.39% vs. 37.60 ± 8.93%; 78.27 ± 8.46% vs. 52.72 ± 2.64%), 3rd (93.80 ± 7.62% vs. 52.94 ± 14.10%; 87.65 ± 10.86% vs. 52.89 ± 1.73%) and 7th (91.36 ± 5.31% vs. 64.09 ± 14.46%; 93.78 ± 3.92% vs. 79.17 ± 1.79%) day after anaesthesia. In the hippocampus of mice exposed to isoflurane, GSP 200 mg/kg increased the total SOD activity on the 1st and 3rd day and reversed the decreased activity of the NR2B/CREB pathway. Discussion and conclusions: These findings suggest that GSP improves isoflurane-induced cognitive dysfunction by protecting against perturbing antioxidant enzyme activities and NR2B/CREB pathway. Therefore, GSP may possess a potential prophylactic role in isoflurane-induced and other oxidative stress-related cognitive decline.

Ethnopharmacological Relevance: Combretum micranthum G. Don (CM) is extensively used in traditional medicine throughout West Africa and commonly known as "long-life herbal tea" or "plant to heal". Further, traditional healers frequently use the title plant to mitigate of renal disorders., Aim of the Study: To explore the nephroprotective property of standardised hydroalcoholic extract of Combretum micranthum in nicotinamide-streptozotocin induced diabetic nephropathy in rats. In addition, in-silico computational experiments were performed with bioactive compounds of the title plant against PPARα and PPARγ., Material and Methods: Male rats were made diabetic by a single intraperitoneal (ip) injection of STZ (50 mg/kg), 15 min after ip administration of NA (100 mg/kg) dissolved in normal saline. The diabetic rats received CM extract (200 and 400 mg/kg p.o.) daily, for eight weeks. Body weights and blood glucose (non-fasting and fasting) of rats were measured weekly. Daily food and water consumption were also measured. After 8 weeks of treatment, urine biochemical parameters such as N-Acetyl-β-D-Glucosaminidase (NAG), urea (UR), uric acid (UA), creatinine (CRE), and serum markers of diabetes, kidney damage and liver damage such as insulin, lipid parameters), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γGT), albumin (Alb), magnesium (Mg 2+ ), calcium (Ca 2+ ), phosphorus (P), were estimated. Blood glycosylated hemoglobin (HbA1 C ) were also estimated. kidney and liver were used for biochemical estimation of oxidative stress markers such as lipid peroxidation, superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity. The kidney and pancreas were used for histopathological study. Further, HPLC chemoprofiling of CM extract and in-silico molecular simulation experiments were performed., Results: At the end of eight weeks, renal damage induced by the consequence of prolong diabetic condition was confirmed by altered levels of serum and urine kidney and liver function markers, oxidative stress markers and histopathological variations in kidney. Treatment with CM extract ameliorated the diabetes mellitus-induced renal biochemical parameters and histopathological changes. Further, HPLC-UV & MS experiments revealed that CM extract contains several bioactive compounds including hyperozide (62.35 μg/mg of extract) and quercitrin (19.07 μg/mg of extract). In-silico experiment exhibited cianidanol (-17.133), epicatechin (-15.107) exhibited higher docking score against PPARα and luteoforol (-11.038), epigallocatechin (-10.736) against PPARγ. Based on docking and drug likeness score, four bioactive compounds were selected for molecular dynamic experiments. Cianidanol and epigallocatechin out of the 30 compounds are concluded as a potential candidate for the treatment of DN through activating PPARα and PPARγ target protein., Conclusions: Taken together, the present study provided the scientific footage for the traditional use of Combretum micranthum., (Copyright © 2020 Elsevier B.V. All rights reserved.)

There is growing research interest in the hypocholesterolemic effect of various food components such as polyphenols. In this study, we examined the effects of oligonol-a low-molecular weight polyphenol extracted from lychee fruit-on cholesterol metabolism in rats under short-term administration. Administration of oligonol for 3 days significantly increased cecum weight and decreased cecal n-butyric acid concentrations in rats. Oligonol also significantly lowered the levels of hepatic cholesterol and increased the levels of total neutral steroids excreted in the feces. It also increased fecal β-muricholic acid significantly, whereas the levels of total acidic steroids remained unchanged. Gene expression of hepatic CYP7A1 (cytochrome P450 family 7 subfamily A member 1) significantly increased following the administration of oligonol. This increase could be ascribed to changes in the expression of farnesoid X receptor, small heterodimer partner, and fibroblast growth factor 15 in ileum. Our data suggest that oligonol induces hypocholesterolemic effects through the inhibition of biliary cholesterol absorption from the intestine and the upregulation of cholesterol catabolism in rats even following short-term administration. Therefore, oligonol may be an important food component for reducing cholesterol level.

The purpose of this review is to examine epigallocatechin-3-gallate (EGCG) regarding its stability in different conditions (pH-value, concentration, temperature), its interactions with common cosmetic ingredients, and its application in the dermatological field. The literature research considered published journal articles (clinical trials and scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) and reference lists of respective articles. Higher concentrations of EGCG were reported to correlate with better stability and the same can be said for low temperatures and pH values. The interaction between EGCG and hyaluronic acid strengthens its antioxidant activities. Titanium dioxide coated with EGCG proved a suitable ingredient in sunscreens. The polyphenol possesses antioxidant properties, which proved effective in the prevention of UV-induced skin damage and to alleviate the symptoms of Imiquimod-induced psoriasis. The three endpoints of this review not only showed interesting results but also highlighted some limitations of EGCG. Studies show that the molecule is unstable, which may hinder its dermatological and cosmetic applications. The reported interactions with cosmetic ingredients were limited. As the health aspects of EGCG are well-reported, ECGC has become a focus of interest for health professionals trying to treat common dermatological diseases., (© 2020 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: Green tea has been used as a traditional medicine to control brain function and digestion. Recent works suggest that drinking green tea could prevent cognitive function impairment. During tea manufacturing processes, such as brewing and sterilization, green tea catechins are epimerized. However, the effects of heat-epimerized catechins on cognitive function are still unknown. To take this advantage, we developed a new green tea extract, high temperature processed-green tea extract (HTP-GTE), which has a similar catechin composition to green tea beverages., Aim of the Study: This study aimed to investigate the effect of HTP-GTE on scopolamine-induced cognitive dysfunction and neuronal differentiation, and to elucidate its underlying mechanisms of action., Materials and Methods: The neuronal differentiation promoting effects of HTP-GTE in SH-SY5Y cells was assessed by evaluating neurite length and the expression level of synaptophysin. The DNA methylation status at the synaptophysin promoter was determined in differentiated SH-SY5Y cells and in the hippocampi of mice. HTP-GTE was administered for 10 days at doses of 30, 100 and 300 mg/kg (p.o.) to mice, and its effects on cognitive functions were measured by Y-maze and passive avoidance tests under scopolamine-induced cholinergic blockade state., Results: HTP-GTE induced neuronal differentiation and neurite outgrowth via the upregulation of synaptophysin gene expression. These beneficial effects of HTP-GTE resulted from reducing DNA methylation levels at the synaptophysin promoter via the suppression of DNMT1 activity. The administration of HTP-GTE ameliorated cognitive impairments in a scopolamine-treated mouse model., Conclusions: These results suggest that HTP-GTE could alleviate cognitive impairment by regulating synaptophysin expression and DNA methylation levels. Taken together, HTP-GTE would be a promising treatment for the cognitive impairment observed in dysfunction of the cholinergic neurotransmitter system., Competing Interests: Declaration of competing interest None of the authors has any conflicts of interest regarding this study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The young leaves of green tea become lighter in color than usual when protected from sunlight by a shading net for about two weeks while growing. These leaves are called "shaded white leaf tea" or SWLT. In the eluate of SWLT, the amount of amino acids (361 mg/L) was significantly higher than that in regular tea (53.5 mg/L). Since theanine and arginine, the first and second most abundant amino acids in SWLT, have significant antistress effects, we examined the antistress effect of SWLT on humans. SWLT or placebo green tea (3 g) was eluted with room-temperature water (500 mL). Participants consumed the tea for one week prior to pharmacy practice and continued for 10 days in the practice period. The state-trait anxiety inventory, an anxiety questionnaire, tended to be scored lower in the SWLT group than the placebo, but other stress markers showed no differences. The effect of the difference in SWLT components examined with mice showed that aspartic acid and asparagine, which are abundant in SWLT, counteracted the antistress effects of theanine and arginine. Large amounts of caffeine also interfered with SWLT's antistress effect. Thus, SWLT, which is high in caffeine and amino acids, suppressed depressant behavior in mice.

In this study, a capillary electrophoresis-based online immobilized enzyme microreactor was developed for evaluating the inhibitory activity of green tea catechins and tea polyphenol extracts on trypsin. The immobilized trypsin activity and other kinetic parameters were evaluated by measuring the peak area of the hydrolyzate of chromogenic substrate S-2765. The results indicated that the activity of the immobilized trypsin remained approximately 90.0% of the initial immobilized enzyme activity after 30 runs. The value of Michaelis-Menten constant (K m ) was (0.47 ± 0.08) mM, and the half-maximal inhibitory concentration (IC 50 ) and inhibition constant (K i ) of benzamidine were measured as 3.34 and 3.00 mM, respectively. Then, the inhibitory activity of four main catechins (epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate) and three tea polyphenol extracts (green tea, white tea, and black tea) on trypsin were investigated. The results showed that four catechins and three tea polyphenol extracts had potential trypsin inhibitory activity. In addition, molecular docking results illustrated that epigallocatechin gallate, epicatechin gallate, epicatechin, and epigallocatechin were all located not only in the catalytic cavity, but also in the substrate-binding pocket of trypsin. These results indicated that the developed method is an effective tool for evaluating inhibitory activity of catechins on trypsin., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This work aimed to comprehensively evaluate the potential and effectiveness of deep eutectic solvents (DESs) in the extraction of seven catechins from various tea samples. Different combinations of DES were used, consisting of Girard's reagent T (GrT) in various mixing ratios with organic acids and choline chloride. The yields of the DES extractions were compared with those from ionic liquids and conventional solvent. DES contained malic acid, as the hydrogen bond donors showed a good solubility of catechins with different polarities. In the second part of the study, a solid-phase extraction (SPE) method was applied to the extraction of catechins from tea infusions. The method was applied to the determination of selected catechins in tea leaves and tea infusions. Furthermore, we demonstrated that the proposed procedure works well in the simultaneous monitoring of these polyphenols, which makes it a useful tool in the quality control of tea.

A new derivative of epicatechin glucopyranoside, (2 R ,3 R )-3,7,4'-trihydroxy-5,3'-dimethoxyflavan 7- O - β -d-glucopyranoside ( 1 ), together with three mononuclear phenolic acid esters, methyl orsellinate ( 2 ), ethyl orsellinate ( 3 ) and methyl β -orcinolcarboxylate ( 4 ) were isolated from the bark of Styrax suberifolius . The structures of 1 - 4 were determined on the basis of extensive analysis of NMR and MS spectra combined with chemical hydrolysis. The antifungal activities of the isolated compounds against three plant pathogenic fungi, Alternaria solani , Fusarium oxysporum and Phomopsis cytospore were evaluated using radial growth inhibition assay. Compounds 2 , 3 and 4 exerted selective inhibitory activities against the tested fungi. Among of them, methyl β -orcinolcarboxylate ( 4 ) exhibited obvious inhibitory effect against P. cytospore , with an inhibition rate of 86.72% at 100 μg/ml.

To provide further insight into the antioxidant potential of procyanidins (PCs) from cocoa beans, PC extract was fractionated by several methodologies, including solid phase extraction, Sephadex LH-20 gel permeation, and preparative HPLC using C18 and diol stationary phases. All the isolated fractions were analyzed by UHPLC-QTOF-MS to determine their relative composition. According to our results, classical techniques allowed good separation of alkaloids, catechins, dimers, and trimers, but were inefficient for oligomeric PCs. Preparative C18-HPLC method allowed the attainment of high relative composition of fractions enriched with alkaloids, catechins, and PCs with degree of polymerization (DP) < 4. However, the best results were obtained by preparative diol-HPLC, providing a separation according to the increasing DP. According to the mass spectrometry fragmentation pattern, the nine isolated fractions (Fractions II-X) consisted of exclusively individual PCs and their corresponding isomers (same DP). In summary, an efficient, robust, and fast method using a preparative diol column for the isolation of PCs is proposed. Regarding DPPH • and ABTS •+ scavenging activity, it increases according to the DP; therefore, the highest activity was for cocoa extract > PCs > monomers. Thereby, cocoa procyanidins might be of interest to be used as alternative antioxidants.

The acquired resistance to gefitinib limits its clinical application. Epigallocatechin-3-gallate (EGCG) has been found to enhance the efficacy of gefitinib against resistant. However, the cellular and molecular mechanisms have not been completely illuminated in NSCLC. In this study, a new epigallocatechin gallate derivative (2R,3R-6-methoxycarbonylgallocatechin-3-O-gallate, the following referred to as EGCGD) (1) and three known epigallocatechin gallate compounds including epicatechin-3-O-gallate (2), gallocatechin-3-O-gallate (3) and epigallocatechin-3-O-gallate (4, EGCG) were isolated and identified from Anhua dark tea. The pharmacological studies showed EGCGD was more effective against gefitinib-resistant HCC827-Gef cells compared to that of other three epigallocatechin gallate compounds including EGCG, suggesting that introduction of 6-methoxycarbonyl to EGCG might enhance its antitumor activities. Further study on molecular mechanism showed EGCGD increased the potency of gefitinib against HCC827-Gef cells via suppression of epithelial-Mesenchymal transition (EMT) and dual inhibition of PI3K/mTOR., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Epigallocatechin gallate (EGCG), the main green tea polyphenol, exerts a wide variety of biological actions. Epigenetically, the catechin has been classified as a DNMTs inhibitor, however, its impact on histone modifications and chromatin structure is still poorly understood. The purpose of this study was to find the impact of EGCG on the histone posttranslational modifications machinery and chromatin remodeling in human endothelial cells of both microvascular (HMEC-1) and vein (HUVECs) origin. We analyzed the methylation and acetylation status of histones (Western blotting), as well as assessed the activity (fluorometric assay kit) and gene expression (qPCR) of the enzymes playing a prominent role in shaping the human epigenome. The performed analyses showed that EGCG increases histone acetylation (H3K9/14ac, H3ac), and methylation of both active (H3K4me3) and repressive (H3K9me3) chromatin marks. We also found that the catechin acts as an HDAC inhibitor in cellular and cell-free models. Additionally, we observed that EGCG affects chromatin architecture by reducing the expression of heterochromatin binding proteins: HP1α, HP1γ. Our results indicate that EGCG promotes chromatin relaxation in human endothelial cells and presents a broad epigenetic potential affecting expression and activity of epigenome modulators including HDAC5 and 7, p300, CREBP, LSD1 or KMT2A., Competing Interests: The authors declare no conflict of interest.

In this study, water and chelator-soluble pectic polysaccharide fractions were obtained from white grape skins, aiming to study their impact on the interaction between low polymerized grape seed procyanidins and salivary proteins. Water and chelator-soluble polysaccharide fractions were composed by uronic acids and neutral sugars, mainly arabinose and galactose, with water polysaccharide fraction showing a higher amount of branched pectic polysaccharides. Both polysaccharide fractions were able to mitigate salivary protein-procyanidin interactions, by a competition mechanism, resulting in a decrease of the amount of precipitated protein. Water polysaccharide fraction was the most effective in inhibiting salivary protein precipitation, especially for acidic proline-rich proteins, due to the higher affinity to interact with procyanidins (K A = 22222 M -1 and K A = 365 M -1 for water and chelator polysaccharides, respectively). The interaction between polysaccharides and procyanidins showed to be mainly governed by hydrophobic effect., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background Catechin is one of the secondary metabolites in Camellia sinensis L. that is alternatively produced through in vitro cultures. The in vitro culture product is possibly improved by optimizing the culture medium with the addition of growth regulators and precursors. The purpose of this study was to confirm the success of the secondary catechin metabolite production through the in vitro culture of C. sinensis L in a relatively short time. Methods The secondary catechin metabolite product is obtained in about 40 days. The study was conducted by (1) leaf cutting for inoculation in Murashige and Skoog media with 1 μg/mL of 2,4-dichlorophenoxyacetic acid growth regulator; (2) the inoculation of callus multiplication on the same medium as a partially modified inoculation media condition with the addition of 1 μg/mL of 6-benzylaminopurine (BAP) and 2 μg/mL of 2,4-dichlorophenoxyacetic acid at concentration; (3) callus multiplication developed on a new medium containing phenylalanine precursors (300 μg/mL); (4) testing growth by harvesting the callus and weighing the wet weight of its biomass and (5) identification of the callus qualitatively and quantitatively by using high-performance liquid chromatography (HPLC). Results The level of secondary catechin metabolite produced was 2.54 μg/mL and 12.13 μg/mL in solid and suspension media, respectively. Conclusions It is concluded that the method is effective and efficient in producing catechin product from C. sinensis L.

EGCG is a major pharmacological compound in green tea. Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Inflammation and insulin resistance are involved in the development of the disease. In this study, we investigated the beneficial effect of EGCG on the liver tissue of NAFLD rats induced by a high-fat diet and its underlying mechanism. Thirty Sprague-Dawley rats received a normal diet, a HFD and a HFD+EGCG. The expression levels of inflammatory signaling pathway genes (e.g., TLR4, TRAF6, IKKβ, NF-κB, TNF-α) and insulin signaling transduction pathway genes (e.g., PI3K, AKT, IRS-1, IRS-2) were detected in the liver. We observed that EGCG decreased the triglyceride (TG) concentration in rat livers and suppressed TLR4, TRAF6, IKKβ, p-IKKβ, p-NF-κB, and TNF-α levels compared with those in the HFD group, whereas PI3K, AKT, IRS-1, and IRS-2 indicators were improved. EGCG improves obesity-associated subacute hepatic inflammation states, probably through the TLR4 signaling pathway. Furthermore, EGCG also alleviated hepatic insulin resistance. These data indicate that EGCG improves NAFLD from two ways: inhibition of inflammation and improvement of insulin resistance in liver tissues.

Dasiphora fruticosa L. (Rosaceae), also known as Potentilla fruticosa L. (syn.), is a hardy deciduous shrub widely distributed in the north temperate regions of the world. Three methylene bisflavan-3-ols ( 1 - 3 ), together with a procyanidin dimer, (-)-afzelechin-(4α→8)-(-)-afzelechin ( 4 ) were isolated for the first time from the branches and leaves of the titled plant, in addition to 11 known compounds ( 5 - 15 ). Their structures were elucidated by means of extensive spectroscopic analysis and by comparison with data reported in the literatures. Methylene 6,8-bis(7- O -glucosyl) catechin ( 1 ) was determined to be a new dimeric flavan-3-ol glycoside through a methylene linkage between C-8 and C-8 of two units. At a concentration of 128 μg/mL, the known compounds 9 - 13 exhibited antibacterial activities on Escherichia coli , Staphylococcus aureus subsp. aureus , Salmonella enterica subsp. enterica , and Pseudomonas aeruginosa . Compound 12 also showed certain glucose uptake stimulating activity.

Alzheimer's disease (AD) is characterised by the apoptosis of cholinergic neurons and the consequent attenuation of acetylcholine mediated neurotransmission, resulting in neurodegeneration. Acetyl-cholinesterase (AChE) and butyryl-cholinesterase (BuChE) are attractive therapeutic targets in the treatment of AD since inhibition of these enzymes can be used to restore synaptic concentrations of acetylcholine. Whilst inhibitors for these enzymes such as galantamine and rivastigmine have been approved for use, none are able to halt the progression of AD and are responsible for the production of troublesome side-effects. Efficacious cholinesterase inhibitors have been isolated from natural plant-based compounds with many demonstrating additional benefits beyond cholinesterase inhibition, such as antioxidation and anti-inflammation, which are key parts of AD pathology. In this study, five natural flavan-3-ol (catechin) compounds: ((-)-epicatechin (EC), catechin, (-)-epicatechin-3-gallate (ECG),) (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG), isolated from green tea, were screened for their cholinesterase inhibitory activity using the Ellman assay. The kinetics of inhibition was determined using reciprocal Lineweaver-Burk plots. EGCG was the only compound found to produce statistically significant, competitive inhibition, of both AChE ( p < 0.01) and BuChE ( p < 0.01) with IC50 values of 0.0148 µmol/mL and 0.0251 µmol/mL respectively. These results, combined with previously identified antioxidative and anti-inflammatory properties, highlight the potential use of EGCG in the treatment of AD, provided it can be delivered to cholinergic neurons in therapeutic concentrations. Further testing of EGCG in vivo is recommended to fully characterise the pharmacokinetic properties, optimal method of administration and efficacy of this novel plant-based compound.

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.

Procyanidins are polymeric flavan-3-ones occurring in many plants with antioxidant and other beneficial bioactivities. They are composed of catechin and epicatechin monomeric units connected by single carbon-carbon B-type linkages or A-type linkages containing both carbon-carbon and carbon-oxygen-carbon bonds. Their polymeric structure makes analysis of procyanidin mixtures always difficult. Evaluation of procyanidins according to degree of polymerization (DP) using high-performance liquid chromatography (HPLC) is time-consuming and at best has resolved polymeric families up to DP-17. To expedite studies of procyanidins, the utility of positive ion electrospray ion mobility-mass spectrometry (IM-MS) was investigated for the rapid separation and characterization of procyanidins in mixtures. Applying IM-MS to analyse structurally defined standards containing up to five subunits, procyanidins could be resolved in less than 6 ms not only by degree of polymerization but also by linkage type. A-type procyanidins could be resolved from B-type and both could be at least partially resolved from mixed-type procyanidins of the same DP. IM-MS separated higher order procyanidins with DP of at least 24 from extracts of cranberry. As DP increased, the abundances of multiply-charged procyanidins also increased. During IM-MS of ions of similar m/z, the ion drift times decreased inversely with increasing charge state. Therefore, IM-MS was shown to separate mixtures of procyanidins containing at least 24 interconnected subunits in less than 16 ms, not only according to DP, but also according to linkage type between subunits and charge state., (© 2019 John Wiley & Sons, Ltd.)

Based on ethnopharmacological studies, a lot of plants, as well as its compounds, have been investigated for the potential use as wound healing agents. In Brazil, Curatella americana is traditionally used by local people to treat wounds, ulcers and inflammations. However, to the best of our knowledge, its traditional use in the treatment of wounds has not been validated by a scientific study. Here, some compounds, many of them flavonoids, were identified in the hydroethanolic extract from the leaves of C. americana (HECA) by LC-HRMS and LC-MS/MS. Besides that, solutions containing different concentrations of HECA and a gel produced with this extract were evaluated for its antimicrobial, coagulant and wound healing activities on an excision mouse wound model as well as its acute dermal safety. A total of thirteen compounds were identified in HECA, mainly quercetin, kaempferol and glucoside derivatives of both, besides catechin and epicatechin known as wound healing agents. The group treated with 1% of HECA exhibited highest wound healing activity and best rate of wound contraction confirmed by histopathology results. The present study provides scientific evidence of, this extract (HECA) possess remarkable wound healing activity, thereby, supporting the traditional use., Competing Interests: The authors have declared that no competing interests exist.

A type of molecular-imprinted polymer with magnetic molybdenum disulfide as a base and deep eutectic solvent as a functional monomer (Fe 3 O 4 @MoS 2 @DES-MIP) was prepared with surface molecular imprinting method. It was applied as the adsorbent for the selective recognition and separation of (+)-catechin, (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechin gallate, and (-)-epigallocatechin gallate in green tea in the process of magnetic solid-phase extraction (MSPE) combined with high-performance liquid chromatography (HPLC). The structure of Fe 3 O 4 @MoS 2 @DES-MIP was characterized by Fourier transform infrared spectroscopy and field emission scanning electron microscopy. The adsorption properties and selective recognition ability on (-)-epigallocatechin gallate and the other four structural analogues were examined and compared. The results show that the polymer has excellent selective recognition ability for (-)-epigallocatechin gallate, and its adsorption capacity was much higher than that of structural analogues. The Fe 3 O 4 @MoS 2 @DES-MIP not only has the special recognition ability to template a molecule, but also can be separated by magnets with high separation efficiency and can be used in MSPE., Competing Interests: The authors declare no conflict of interest.

Ultraviolet B (UVB) induces inflammation and causes skin aging. The signs of skin aging, such as wrinkles, discolored spots, loss of skin moisture, and disruption of the skin barrier, are mostly caused by inflammatory signaling among various skin layers. The cells on the outermost surface of the skin are keratinocytes; these cells protect the skin against environmental stress and play an important role in immunomodulation by secreting cytokines in response to environmental stress. In the present study, we found that UVB activates STAT1 to mediate inflammatory signaling, yet STAT1 (S272) and STAT (Y702) shows different responses against UVB exposure. Anhua drak tea is a post-fermented dark tea produced in Anhua and Xinhua country in Hunan province of China. Treatment with 2S,3R-6-methoxycarbonylgallocatechin (MCGE), an epigallocatechin gallate derivative isolated from black tea (Anhua dark tea), effectively suppresses STAT1 activation and inflammatory cytokines, and activates Nrf2 pathway to protect cells from reactive oxygen species production in UVB exposed keratinocyte cells (HaCaT). Interestingly, the effects of MCGE were independent on MAPK signaling pathway. Moreover, MCGE regulates inflammatory cytokines in monocyte-keratinocyte (THP-1, HaCaT) co-culture and macrophage differentiation models. These results suggest that MCGE potentially can be used as a photoprotective agent against UVB-induced inflammatory responses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Green tea supplementation has beneficial health effects. However, its underlying mechanisms, such as effects on modulating the intestinal microbiome and endogenous metabolome, particularly following short-term supplementation, are largely unclear. We conducted an integrative metabolomics study to evaluate the effects of short-term (7-day) supplementation of green tea extract (GTE) or its components, epigallocatechin gallate, caffeine, and theanine, on the caecum microbiota and caecum/skin metabolome in mice. Further, we established an integrative metabolome-microbiome model for correlating gut and skin findings. The effects of short-term supplementation with dietary compounds were evaluated with respect to UV stress response, with GTE showing the most remarkable effects. Biplot analysis revealed that Bifidobacteria and Lactobacillus spp. were considerably influenced by short-term GTE supplementation, while Clostridium butyricum was significantly increased by UV stress without supplementation. GTE supplementation helped the skin metabolome defend against UV stress. Interestingly, a significant positive correlation was observed between caecum bacteria (Bifidobacteria, Lactobacillus spp.) and metabolites including skin barrier function-related skin metabolites, caecal fatty acids, and caecal amino acids. Overall, 7-day GTE supplementation was sufficient to alter the gut microbiota and endogenous caecum/skin metabolome, with positive effects on UV stress response, providing insight into the mechanism of the prebiotic effects of GTE supplementation.

Catechins in green tea are well-known to be effective in reducing the risk of obesity. The purpose of this study was to elucidate the effects of catechins present in green tea on adipocyte differentiation and mature adipocyte metabolism. Treatment of 3T3-L1 mouse adipocyte during differentiation adipocytes with (-)-epigallocatechin (EGC) and gallic acid (GA) resulted in dose-dependent inhibition of adipogenesis. Specifically, EGC increased adiponectin and uncoupling protein 1 (UCP1) transcription in mature adipocytes. Transcription levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were not significantly impacted by either of the compounds. These results suggest that the EGC is the most effective catechin having anti-obesity activity. Finally, EGC is an attractive candidate component for remodeling obesity., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Considering the therapeutic potential of phenolic compounds, the purpose of the present study was to investigate the mechanisms involved in the relaxation induced by cryptostrobin and catechin, isolated from Eugenia mattosii D. Legrand leaves, in the aorta of spontaneously hypertensive rats (SHR)., Methods: The thoracic aorta was isolated from SHR and kept in the organ bath system by recording contractile or relaxant responses., Results: The addition of cumulative concentrations of cryptostrobin and catechin induced endothelium-dependent and-independent relaxation in aorta rings from SHR, as well as both compounds were effective in reducing phenylephrine-induced contraction. Pretreatment of aortic rings with N ω -nitro-l-arginine methylester (L-NAME, an inhibitor of nitric oxide synthase) or 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an inhibitor of soluble guanylate cyclase), resulted in a significant change of relaxant effect induced by catechin, and a slight influence on cryptostrobin-induced relaxation. Muscarinic receptor and potassium channels are involved in catechin-induced relaxation as assessed using atropine (a muscarinic receptor antagonist), tetraethylammonium (a non-selective K + channel blocker) and glibenclamide (an ATP-sensitive K + channel blocker). Conversely, cryptostrobin, but not catechin, blunted the contraction induced by the addition of phenylephrine in a calcium-free solution. Besides that, cryptostrobin attenuated the contraction of rat aorta rings induced by internal Ca 2+ release and external Ca 2+ influx., Conclusions: These findings indicated that cryptostrobin and catechin alter vascular smooth muscle reactivity, and this effect may be involved, at least in part, by enhancing the endothelium NO/cGMP pathway and potassium channels activation. In addition, cryptostrobin reduced the phenylephrine, KCl and CaCl 2 -induced contractions in a calcium-free solution., (Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

Aims: Pseudomonas fluorescens are important psychrotrophic food spoilage bacteria that are frequently detected in dairy, meat and aquatic products. Quorum sensing (QS) is an intercellular communication and gene regulation mechanism that enables bacteria to monitor their cell densities and regulate a variety of physiological processes. Hence, targeting the bacterial QS system might be a feasible approach to improve food quality and safety by regulating the spoilage caused by P. fluorescens., Methods and Results: In this study, we screened a food-derived three-dimensional (3D) compound database to search for potential QS inhibitors (QSIs) with higher security. The 3D structures of LuxI- and LuxR-type proteins of P. fluorescens P07 were used as targets to screen for QSIs. A total of 25 compounds with high docking scores were tested for their anti-QS activities by indicator strains. The results show that 19 compounds possessed anti-QS activities. Among them, (+)-catechin had the strongest anti-QS activity. The results show that (+)-catechin significantly inhibited the production of extracellular enzymes, swimming motility, biofilm formation, acyl-homoserine lactones and extracellular polymeric substances (EPSs) of P. fluorescens P07. The inhibitory mechanism of (+)-catechin on the QS system of P. fluorescens P07 was discussed in the context of molecular docking analysis and real-time quantitative PCR (RT-qPCR)., Conclusions: Virtual screening was useful in finding novel QSIs with high security of P. fluorescens P07 from a food-derived 3D compound database. The high hit rate suggested that foods are rich sources of QSIs, and have great potential for exploration., Significance and Impact of the Study: The modelled LuxI- and LuxR-type proteins could be used as targets to discover P. fluorescens P07 QSIs. (+)-catechin, (-)-epicatechin, propyl gallate, hesperidin and lycopene which were identified as potent QSIs, and may be applied in food preservation and biofilm elimination., (© 2019 The Society for Applied Microbiology.)

Theaflavins (TFs) are derived from black tea, an important source of dietary polyphenols. Although the potential interactions between dietary polyphenols and drugs have been demonstrated through in vitro and in vivo studies, little information is available concerning the influence of TFs on drug disposition. Organic anion transporting polypeptide 2B1 (OATP2B1) is expressed in human enterocytes and plays a role in the intestinal absorption of numerous drugs. The current study evaluated the effects of black tea extracts on the pharmacokinetics of rosuvastatin in rats, and investigated the effect of four major TFs (theaflavin, theaflavin-3-gallate, theaflavin-3'-gallate and theaflavin-3,3'-digallate) on the transport activity of OATP2B1. Black tea extracts significantly decreased the maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC 0 - 8 ) of rosuvastatin by 48% and 37%, respectively (p < 0.001 and p < 0.01, respectively). Moreover, OATP2B1-mediated rosuvastatin and estrone-3-sulfate uptake was significantly reduced in the presence of TFs. A kinetic study revealed that the uptake efficiency (in terms of V max /K m ) of rosuvastatin was decreased following treatment with TFs. Black tea extracts also reduced OATP2B1-mediated rosuvastatin uptake. These results suggest that black tea reduces the plasma concentrations of rosuvastatin by inhibiting the intestinal OATP2B1-mediated transport of rosuvastatin., (© 2019 John Wiley & Sons, Ltd.)

Background: The present study evaluated the antinociceptive effect of the bark of Artocarpus lacucha, which is used for the treatment of stomachache, headache and boils in the traditional system of medicine., Methods: The antinociceptive activity was investigated by the tail immersion, hot plate, acetic acid- & formalin-induced nociception and carrageenan-induced paw edema tests using a hydro-methanolic extract of A. lacucha bark. The plant extract was found to contain a substantial amount of phenolic compounds according to the total phenolic and flavonoid content assay. A phenolic metabolite, (+)-catechin, has been isolated using different chromatographic techniques. The compound was characterized with 1D and 2D NMR spectroscopic data. (+)-catechin, isolated from A. lacucha was assessed for antinociceptive effects swiss albino mice. Furthermore, the possible involvement of opioid receptors and ATP-sensitive K + channel for the effect of the plant extract and (+)-catechin has been justified using naloxone and glibenclamide, respectively., Results: Oral administration (p.o) of the plant extract (50-200 mg/Kg b.w.) resulted in significant thermal pain protection in the hot plate and tail immersion tests. The action of the plant extract was significantly antagonized by naloxone, a non-selective opioid antagonist, in the hot plate and tail immersion tests, which supports the involvement of opioid receptors. Both the plant extract and (+)-catechin, (50-200 mg/Kg b.w., p.o.) significantly diminished the acetic acid- & formalin-induced nociception, and carrageenan-induced paw edema. Glibenclamide, an ATP-sensitive K + channel blocker, significantly reversed their effect in the acetic acid-induced writhing test which indicates the participation of ATP-sensitive K + channel system., Conclusions: The investigation revealed potential central and peripheral antinociceptive effects of A. lacucha bark supports its applications in the traditional system of medicine.

In the present study, we aimed to develop a novel fermented tea (NFT) product and to evaluate their in vitro antioxidant potential and chemical composition. We found that NFT contained a high level of total phenolic compounds (102.98 mg gallic acid equivalents/g extract) and exhibited diverse antioxidant activities, such as scavenging of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and hydroxyl radicals, as well as reducing power. The total catechins in NFT were comparable to those of Lipton black tea (LBT), but lower than those of Boseong green tea (BGT) or Tieguanyin oolong tea (TOT). Among all catechins tested, epigallocatechin (EGC) and epigallocatechin-3-O-gallate (EGCG) were the predominant compounds in NFT. In particular, the contents of total theaflavins (TFs), theaflavin (TF), theaflavin-3-gallate (TF3G), and theaflavin-3'-gallate (TF3'G) in NFT were significantly higher than that of BGT, TOT, or LBT. NFT had the highest level of total essential amino acid and γ-aminobutyric acid (GABA) compared with BGT, TOT and LBT. Furthermore, the sensory evaluation results showed that NFT had satisfactory color, aroma, taste, and overall acceptability scores. Our results highlight the potential usefulness of this novel fermented tea as a nutraceutical food/ingredient with special functional activities.

Background: Synovial fluid components, especially lipids, can trigger oxidation of ultrahigh-molecular-weight polyethylene (UHMWPE) artificial joint components in vivo. The use of antioxidants such as vitamin E effectively diminishes the oxidative cascade by capturing free radicals and reducing the oxidation potential of UHMWPE implants. Using a thermo-oxidative aging method, we recently found that tea polyphenols can enhance the oxidation resistance of irradiated UHMWPE in comparison with commercial vitamin E. However, it is yet unknown whether tea polyphenols can reduce lipid-induced oxidation., Questions/purposes: We explored whether tea polyphenol-stabilized UHMWPE would exhibit (1) lower squalene absorption; (2) stronger oxidation resistance; and (3) lower content of free radicals than vitamin E-stabilized UHMWPE under a physiologically-motivated in vitro accelerated-aging model., Methods: Tea polyphenol (lipid-soluble epigallocatechin gallate [lsEGCG]) and vitamin E were blended with UHMWPE powders followed by compression molding and electron beam irradiation at 100 and 150 kGy. Small cubes (n = 3, 60 mg, 4 × 4 × 4 mm) cut from the blocks were doped in squalene at 60°, 80°, 100°, and 120° C for 2 hours. Gravimetric change of the cubes after squalene immersion was measured to assess absorption. Thin films (n = 3, ∼60 μm) were also microtomed from the blocks and were doped at 120° C for 24 hours. Oxidation induction time (n = 3, 5 mg of material from the cubes) and incipient oxidation temperature (n = 3, thin films) were obtained to determine the oxidation stability. Signal intensity of the free radicals, obtained by electron spin resonance spectroscopy, was used to qualitatively rank the antioxidant ability of vitamin E and lsEGCG., Results: Squalene absorption was comparable between lsEGCG/UHMWPE and vitamin E/UHMWPE at a given temperature and radiation dose. The oxidation induction time of 100 kGy-irradiated UHMWPE was increased with lsEGCG compared with vitamin E except at 120° C. For example, the oxidation induction time value of 100 kGy-irradiated lsEGCG/UHMWPE immersed at 60 C was 25.3 minutes (24.2-27.8 minutes), which was 8.3 minutes longer than that of 100 kGy-irradiated vitamin E/UHMWPE which was 17.0 minutes (15.0-17.1 minutes) (p = 0.040). After squalene immersion at 120° C, the incipient oxidation temperature of 100 and 150 kGy irradiated lsEGCG/UHMWPE was 234° C (227-240° C) and 227° C (225-229° C), which was higher than vitamin E-stabilized counterparts with value of 217° C (214-229° C; p = 0.095) and 216° C (207-218° C; p = 0.040), respectively. The electron spin resonance signal of 150 kGy irradiated lsEGCG/UHMWPE was qualitatively weaker than that of 150 kGy irradiated vitamin E/UHMWPE., Conclusions: lsEGCG-stabilized UHMWPE demonstrated higher oxidation resistance than vitamin E-stabilized UHMWPE after squalene immersion, likely because lsEGCG donates more protons to eliminate macroradicals than vitamin E., Clinical Relevance: Our in vitro findings provide support that lsEGCG may be effective in protecting against oxidation that may be associated with synovial fluid-associated oxidation of highly crosslinked UHMWPE joint replacement components.