CsMYBL2 homologs modulate the light and temperature stress-regulated anthocyanin and catechins biosynthesis in tea plants (Camellia sinensis).

Anthocyanin and catechin production in tea (Camellia sinensis) leaves can positively affect tea quality; however, their regulatory mechanisms are not fully understood. Here we report that, while the CsMYB75- or CsMYB86-directed MYB-bHLH-WD40 (MBW) complexes differentially activate anthocyanin or catechin biosynthesis in tea leaves, respectively, CsMYBL2a and CsMYBL2b homologs negatively modified the light- and temperature-induced anthocyanin and catechin production in both Arabidopsis and tea plants. The MBW complexes activated both anthocyanin synthesis genes and the downstream repressor genes CsMYBL2a and CsMYBL2b. Overexpression of CsMYBL2b, but not CsMYBL2a, repressed Arabidopsis leaf anthocyanin accumulation and seed coat proanthocyanin production. CsMYBL2b strongly and CsMYBL2a weakly repressed the activating effects of CsMYB75/CsMYB86 on CsDFR and CsANS, due to their different EAR and TLLLFR domains and interactions with CsTT8/CsGL3, interfering with the functions of activating MBW complexes. CsMYBL2b and CsMYBL2a in tea leaves play different roles in fine-tuning CsMYB75/CsMYB86-MBW activation of biosynthesis of anthocyanins and catechins, respectively. The CsbZIP1-CsmiR858a-CsMYBL2 module mediated the UV-B- or cold-activated CsMYB75/CsMYB86 regulation of anthocyanin/catechin biosynthesis by repressing CsMYBL2a and CsMYBL2b. Similarly, the CsCOP1-CsbZIP1-CsPIF3 module, and BR signaling as well, mediated the high temperature repression of anthocyanin and catechin biosynthesis through differentially upregulating CsMYBL2b and CsMYBL2a, respectively. The present study provides new insights into the complex regulatory networks in environmental stress-modified flavonoid production in tea plant leaves.

Gut microbiota-mediated metabolism of green tea catechins and the biological consequences: An updated review.

Multiple beneficial effects have been attributed to green tea catechins (GTCs). However, the bioavailability of GTCs is generally low, with only a small portion directly absorbed in the small intestine. The majority of ingested GTCs reaches the large intestinal lumen, and are extensively degraded via biotransformation by gut microbiota, forming many low-molecular-weight metabolites such as phenyl-γ-valerolactones, phenolic acids, butyrate, and acetate. This process not only improves the overall bioavailability of GTC-derived metabolites but also enriches the biological activities of GTCs. Therefore, the intra- and inter-individual differences in human gut microbiota as well as the resulting biological contribution of microbial metabolites are crucial for the ultimate health benefits. In this review, the microbial degradation of major GTCs was characterized and an overview of the in vitro models used for GTC metabolism was summarized. The intra- and inter-individual differences of human gut microbiota composition and the resulting divergence in the metabolic patterns of GTCs were highlighted. Moreover, the potential beneficial effects of GTCs and their gut microbial metabolites were also discussed. Overall, the microbial metabolites of GTCs with higher bioavailability and bioactive potency are key factors for the observed beneficial effects of GTCs and green tea consumption.

Combination of tea catechins and ornithine effectively activates the urea cycle: an in vitro and human pilot study.

PURPOSE: Accumulation of ammonia causes central and peripheral fatigue. This study aimed to investigate the synergistic effect of tea catechins and low-dose ornithine in activating the urea cycle to reduce blood ammonia levels during exercise. METHODS: We used hepatocyte-like cells derived from human-induced pluripotent stem (iPS) cells to assess the effect of tea catechins combined with ornithine on urea cycle activity. The urea production and expression of key genes involved in the metabolism of urea were investigated. We then examined the synergistic improvement in ammonia metabolism by tea catechins in combination with ornithine in a human pilot study. RESULTS: Tea catechins combined with ornithine increased urea cycle activity in hepatocyte-like cells derived from human iPS cells. Intake of 538.6 mg of tea catechins with 1592 mg of ornithine for 2 consecutive days during exercise loading suppressed the exercise-induced increase in the blood ammonia concentration as well as stabilized blood glucose levels. CONCLUSION: Controlling the levels of ammonia, a toxic waste produced in the body, is important in a variety of situations, including exercise. The present study suggests that a heterogeneous combination of polyphenols and amino acids efficiently suppresses elevated ammonia during exercise in humans by a mechanism that includes urea cycle activation. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (No. UMIN000035484, dated January 8, 2019).

Therapeutic potentialities of green tea (Camellia sinensis) in ischemic stroke: biochemical and molecular evidence.

Ischemic stroke is a leading cause of disability and death in patients. Despite considerable recent advances in the treatment of ischemic stroke, only a limited number of effective neuroprotective agents are available for stroke. Green tea (Camellia sinensis) is a popular herbal plant, and numerous studies have indicated its health benefits for several diseases. Green tea is of interest due to its high content of catechin derivatives, including epicatechin, gallocatechin, epicatechin gallate, epigallocatechin, and epigallocatechin-3-gallate. This review tried to develop a feasible background for the potential effects of green tea and its bioactive derivatives concerning protection against ischemic stroke. Green tea's antioxidants, anti-inflammatory, anti-apoptotic, and neuroprotective effects are believed to be efficacious in stroke treatment. Evidence supports the idea that green tea can be used to assist in treating ischemic stroke.

A novel optimized eco-friendly simple spectrofluorimetric method for the determination of total catechins in green tea extract: Application to commercial tablet.

Green tea extract (GTE) contains antioxidants that are present in green tea. The active constituents of green tea extract are catechins. This study demonstrates a spectrofluorimetric method for measuring GTE's catechin concentration based on its native fluorescence. To design a quick, sensitive, and ecological spectrofluorimetric approach, all features were investigated and adjusted. This method relies on determining the GTE ethanolic solution's native fluorescence at 312 nm after excitation at 227 nm. The calibration graph displayed a linear regression for values between 0.05 and 1.0 µg mL-1. The detection and quantification limits of the proposed technique were 0.008 and 0.026 µg mL-1, respectively. Two pure catechins present in GTE, (-)-epicatechin and (-)-epigallocatechin gallate, were examined by the proposed method. The analytical estimation of GTE in the pharmaceutical tablet was achieved effectively using this approach. An adequate degree of agreement was found when the findings were compared to those obtained by the comparative technique. Therefore, the novel strategy may be used in the GTE quality control study with minimal risks to people or the environment. The quantum yields of catechins were estimated. The validated technique was accepted by the International Council of Harmonization criteria.

A Comprehensive Strategy for Metabolites Profiling of Flowers and Leaves from Camellia tienii, an Endemic Golden Tea of Vietnam.

Golden camellia is defined as a species of the Camellia genus with yellow flowers, which have long been used as a medicine, food, and cosmetic in many Asian countries. To date, more than 50 golden camellia species are considered endemic in Vietnam; however, more information is needed about its chemical constituents and biological activity. This work aims to unveil the potential of Camellia tienii Ninh, a golden camellia species, as an herbal beverage by examining the presence and abundance of chemical components in flowers and leaves. A comprehensive strategy has been developed using both liquid and gas chromatography coupled with mass spectrometry. Specifically, LC-MS-based widely targeted analyses were opted to characterize 158 polar metabolites belonging mainly to flavonoids, catechins, and amino acids classes, and an untargeted approach using GC-MS annotated 42 major volatile compounds such as terpenes and fatty acids. The extensive profile revealed by these techniques could help understand the significant discrimination between two organs. C. tienii flowers accumulated more flavonoids, amino acids, and fatty acids, while leaves contain more terpenes, suggesting different pharmacological properties of these materials. Overall, this pipeline can be applied for other Camellia species and valorization of these valuable resources for health benefits purposes.

How Tea Plant Defends Against Blister Blight Disease: Facts Revealed and Unexplored Horizons.

Tea (Camellia sinensis [L.] O. Kuntze) is cultivated as a beverage crop. Despite being a hardy perennial, the tea plant is susceptible to various biotic stresses. Among them, the foliar disease blister blight (BB) is considered the most serious threat to the tea industry, particularly in Asia. BB caused by Exobasidium vexans (Basidiomycetes) was first reported from Northern India in 1868 and gradually established in other tea-growing countries. The fungus E. vexans attacks young harvestable shoots and causes 20 to 50% crop loss. Over the past 150 years, scientific research has delved into various aspects of BB disease, including pathogen biology, disease cycle, epidemiology, disease forecasting, crop loss assessment, and disease management strategies. In a recent shift in research focus, scientists have begun to investigate the resistance mechanisms of tea plants against BB and apply this knowledge to commercial tea cultivation. Although progress has been significant in understanding the fundamental aspects of BB resistance, the detailed molecular mechanisms driving this resistance remain under investigation. This paper focuses on the current understanding of defense mechanisms employed by tea plants against E. vexans and, conversely, how E. vexans overcomes these defenses. Furthermore, we discuss the application of plant resistance strategies in commercial tea cultivation. Lastly, we identify existing research gaps and propose future research directions in the field.

Intestinal Epithelial Co-Culture Sensitivity to Pro-Inflammatory Stimuli and Polyphenols Is Medium-Independent.

The complexification of in vitro models requires the compatibility of cells with the same medium. Since immune cells are the most sensitive to growth conditions, growing intestinal epithelial cells in their usual medium seems to be necessary. This work was aimed at comparing the sensitivity of these epithelial cells to pro-inflammatory stimuli but also to dietary polyphenols in both DMEM and RPMI-1640 media. Co-cultures of Caco-2 and HT29-MTX cells were grown for 21 days in the two media before their stimulation with a cocktail of TNF-α (20 ng/mL), IL-1ß (1 ng/mL), and IFN-γ (10 ng/mL) or with LPS (10 ng/mL) from E. coli (O111:B4). The role of catechins (15 µM), a dietary polyphenol, was evaluated after its incubation with the cells before their stimulation for 6 h. The RPMI-1640 medium did not alter the intensity of the inflammatory response observed with the cytokines. By contrast, LPS failed to stimulate the co-culture in inserts regardless of the medium used. Lastly, catechins were unable to prevent the pro-inflammatory response observed with the cytokines in the two media. The preservation of the response of this model of intestinal epithelium in RPMI-1640 medium is promising when considering its complexification to evaluate the complex cellular crosstalk leading to intestinal homeostasis.

Fabrication and characterization of electrospun catechins-loaded nanofibres for fortification of milk.

Catechins in their free form are bitter in taste, and undergo deterioration and oxidation during processing and storage that limit their use as nutraceuticals in foods. Therefore, catechins were electrospun using zein as encapsulating polymer into nanofibres at 15, 18 and 21% w/w concentrations, 16, 20 and 24 kV applied voltage and 0.5 and 1.0 mL/h feed rate. The electrospinning conditions were optimized using Taguchi L18 (21 × 32) design. Encapsulation efficiency as high as 92.8% and mean fibre diameter as low as 95.2 nm were obtained at 18% concentration of zein, 0.5 mL/h feed rate and 20 kV applied voltage. Scanning electron and atomic force micrographs revealed that the nanofibres produced at zein concentration of 18% and above were clean and beadfree, with cylindrical morphology and non-porous topography. The hydrodynamic diameter, zeta potential and polydispersity index of catechins-loaded nanofibres at optimized conditions were 172.3 nm, -26.3 mV and 0.15. FTIR spectroscopy and X-ray diffractometry confirmed that catechins were encapsulated within the nanofibres. The catechins got released from loaded nanofibres in a controlled and sustained manner, while their antioxidant property was retained. The physico-chemical and sensory qualities of milk were not affected after fortification with catechins-loaded nanofibres. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05891-0.

Structural determinants of the interactions of catechins with Aß oligomers and lipid membranes.

The aberrant self-assembly of intrinsically disordered proteins (IDPs) into soluble oligomers and their interactions with biological membranes underlie the pathogenesis of numerous neurodegenerative diseases, including Alzheimer's disease. Catechins have emerged as useful tools to reduce the toxicity of IDP oligomers by modulating their interactions with membranes. However, the structural determinants of catechin binding to IDP oligomers and membranes remain largely elusive. Here, we assemble a catechin library by combining several naturally occurring chemical modifications and, using a coupled NMR-statistical approach, we map at atomic resolution the interactions of such library with the Alzheimer's-associated amyloid-beta (Aß) oligomers and model membranes. Our results reveal multiple catechin affinity drivers and show that the combination of affinity-reducing covalent changes may lead to unexpected net gains in affinity. Interestingly, we find that the positive cooperativity is more prevalent for Aß oligomers than membrane binding, and that the determinants underlying catechin recognition by membranes are markedly different from those dissected for Aß oligomers. Notably, we find that the unanticipated positive cooperativity arises from the critical regulatory role of the gallate catechin moiety, which recruits previously disengaged substituents into the binding interface and leads to an overall greater compaction of the receptor-bound conformation. Overall, the previously elusive structural attributes mapped here provide an unprecedented foundation to establish structure-activity relationships of catechins.

Gut microbiota as a driver of the interindividual variability of cardiometabolic effects from tea polyphenols.

Tea polyphenols have been extensively studied for their preventive properties against cardiometabolic diseases. Nevertheless, the evidence of these effects from human intervention studies is not always consistent, mainly because of a large interindividual variability. The bioavailability of tea polyphenols is low, and metabolism of tea polyphenols highly depends on individual gut microbiota. The accompanying reciprocal relationship between tea polyphenols and gut microbiota may result in alterations in the cardiometabolic effects, however, the underlying mechanism of which is little explored. This review summarizes tea polyphenols-microbiota interaction and its contribution to interindividual variability in cardiometabolic effects. Currently, only a few bacteria that can biodegrade tea polyphenols have been identified and generated metabolites and their bioactivities in metabolic pathways are not fully elucidated. A deeper understanding of the role of complex interaction necessitates fully individualized data, the ntegration of multiple-omics platforms and development of polyphenol-centered databases. Knowledge of this microbial contribution will enable the functional stratification of individuals in the gut microbiota profile (metabotypes) to clarify interindividual variability in the health effects of tea polyphenols. This could be used to predict individual responses to tea polyphenols consumption, hence bringing us closer to personalized nutrition with optimal dose and additional supplementation of specific microorganisms.

Regulation of biosynthesis of the main flavor-contributing metabolites in tea plant (Camellia sinensis): A review.

In the process of adapting to the environment, tea plants (Camellia sinensis) endow tea with unique flavor and health functions, which should be attributed to secondary metabolites, including catechins, L-theanine, caffeine and terpene volatiles. Since the content of these flavor-contributing metabolites are mainly determined by the growth of tea plant, it is very important to understand their alteration and regulation mechanisms. In the present work, we first summarize the distribution, change characteristics of the main flavor-contributing metabolites in different cultivars, organs and under environmental stresses of tea plant. Subsequently, we discuss the regulating mechanisms involved in the biosynthesis of these metabolites based on the existing evidence. Finally, we propose the remarks and perspectives on the future study relating flavor-contributing metabolites. This review would contribute to the acceleration of research on the characteristic secondary metabolites and the breeding programs in tea plants.

Current extraction, purification, and identification techniques of tea polyphenols: An updated review.

Tea, as a beverage, has been reputed for its health benefits and gained worldwide popularity. Tea polyphenols, especially catechins, as the main bioactive compounds in tea, exhibit diverse health benefits and have wide applications in the food industry. The development of tea polyphenol-incorporated products is dependent on the extraction, purification, and identification of tea polyphenols. Recent years, many green and novel extraction, purification, and identification techniques have been developed for the preparation of tea polyphenols. This review, therefore, introduces the classification of tea and summarizes the main conventional and novel techniques for the extraction of polyphenols from various tea products. The advantages and disadvantages of these techniques are also intensively discussed and compared. In addition, the purification and identification techniques are summarized. It is hoped that this updated review can provide a research basis for the green and efficient extraction, purification, and identification of tea polyphenols, which can facilitate their utilization in the production of various functional food products and nutraceuticals.

Recent insights on tea metabolites, their biosynthesis and chemo-preventing effects: A review.

Tea manufactured from the cultivated shoots of Camellia sinensis (L.) O. Kuntze is the most commonly consumed nonalcoholic drink around the world. Tea is an agro-based, environmentally sustainable, labor-intensive, job-generating, and export-oriented industry in many countries. Tea includes phenolic compounds, flavonoids, alkaloids, vitamins, enzymes, crude fibers, protein, lipids, and carbohydrates, among other biochemical constituents. This review described the nature of tea metabolites, their biosynthesis and accumulation with response to various factors. The therapeutic application of various metabolites of tea against microbial diseases, cancer, neurological, and other metabolic disorders was also discussed in detail. The seasonal variation, cultivation practices and genetic variability influence tea metabolite synthesis. Tea biochemical constituents, especially polyphenols and its integral part catechin metabolites, are broadly focused on potential applicability for their action against various diseases. In addition to this, tea also contains bioactive flavonoids that possess health-beneficial effects. The catechin fractions, epigallocatechin 3-gallate and epicatechin 3-gallate, are the main components of tea that has strong antioxidant and medicinal properties. The synergistic function of natural tea metabolites with synthetic drugs provides effective protection against various diseases. Furthermore, the application of nanotechnologies enhanced bioavailability, enhancing the therapeutic potential of natural metabolites against numerous diseases and pathogens.

α-Glucosidase inhibition by green, white and oolong teas: in vitro activity and computational studies.

Natural α-glucosidase inhibitors from plant-based foods such as catechins offer an attractive strategy for their potential anti-diabetic effects. In this study, infusions of three different tea types (green, white, and oolong) were investigated for their total phenolic (TPC) and catechins (EGCG, ECG, EGC, and EC) content, and for their α-glucosidase inhibitory activities. We observed that the level of TPC in white tea was significantly higher compared to oolong and green tea, which suggests higher content of EGCG and ECG catechins in fresh young leaves. Our findings showed that the higher content of such catechins in the infusion of white tea well correlated with a strong inhibition of α-glucosidase, and such inhibition was demonstrated to be more effective than the FDA-approved drug acarbose. Then, we computationally explored the molecular requirements for enzyme inhibition, especially for the most active catechins EGCG and ECG, as well as their disposition/stability within the active site.

Effects of green tea catechins and exercise training on body composition parameters.

The impact of phytochemicals, as green tea catechins, on body composition measures has become a relevant topic as ongoing epidemiological evidence suggests their potential role in weight loss. Although catechins have been shown to modulate fat and energy metabolism, clinical effects of green tea consumption still remain controversial. Given the role played by physical exercise in weight management, it is important to determine whether the association of catechins and exercise is able to improve outcomes over and above the beneficial effects of exercise alone. Considering that scientific findings on this topic are not entirely consistent, aim of the present review was to assess the current scientific literature regarding the interplay between green tea catechins and exercise in overweight and obese populations. In particular, it was evaluated whether the addition of green tea supplementation to exercise training was able to further improve the exercise-induced changes in body composition parameters.

Catechin versus MoS2 Nanoflakes Functionalized with Catechin: Improving the Sperm Fertilizing Ability-An In Vitro Study in a Swine Model.

Nowadays, the adoption of In Vitro Fertilization (IVF) techniques is undergoing an impressive increase. In light of this, one of the most promising strategies is the novel use of non-physiological materials and naturally derived compounds for advanced sperm preparation methods. Here, sperm cells were exposed during capacitation to MoS2/Catechin nanoflakes and catechin (CT), a flavonoid with antioxidant properties, at concentrations of 10, 1, 0.1 ppm. The results showed no significant differences in terms of sperm membrane modifications or biochemical pathways among the groups, allowing the hypothesis that MoS2/CT nanoflakes do not induce any negative effect on the parameters evaluated related to sperm capacitation. Moreover, the addition of CT alone at a specific concentration (0.1 ppm) increased the spermatozoa fertilizing ability in an IVF assay by increasing the number of fertilized oocytes with respect to the control group. Our findings open interesting new perspectives regarding the use of catechins and new materials obtained using natural or bio compounds, which could be used to implement the current strategies for sperm capacitation.

Catechins and Proanthocyanidins Involvement in Metabolic Syndrome.

Recent studies on natural antioxidant compounds have highlighted their potentiality against various pathological conditions. The present review aims to selectively evaluate the benefits of catechins and their polymeric structure on metabolic syndrome, a common disorder characterized by a cluster of three main risk factors: obesity, hypertension, and hyperglycemia. Patients with metabolic syndrome suffer chronic low inflammation state and oxidative stress both conditions effectively countered by flavanols and their polymers. The mechanism behind the activity of these molecules has been highlighted and correlated with the characteristic features present on their basic flavonoidic skelethon, as well as the efficient doses needed to perform their activity in both in vitro and in vivo studies. The amount of evidence provided in this review offers a starting point for flavanol dietary supplementation as a potential strategy to counteract several metabolic targets associated with metabolic syndrome and suggests a key role of albumin as flavanol-delivery system to the different target of action inside the organism.

Identification of Catechins' Binding Sites in Monomeric Aß42 through Ensemble Docking and MD Simulations.

The assembly of the amyloid-ß peptide (Aß) into toxic oligomers and fibrils is associated with Alzheimer's disease and dementia. Therefore, disrupting amyloid assembly by direct targeting of the Aß monomeric form with small molecules or antibodies is a promising therapeutic strategy. However, given the dynamic nature of Aß, standard computational tools cannot be easily applied for high-throughput structure-based virtual screening in drug discovery projects. In the current study, we propose a computational pipeline-in the framework of the ensemble docking strategy-to identify catechins' binding sites in monomeric Aß42. It is shown that both hydrophobic aromatic interactions and hydrogen bonding are crucial for the binding of catechins to Aß42. Additionally, it has been found that all the studied ligands, especially EGCG, can act as potent inhibitors against amyloid aggregation by blocking the central hydrophobic region of Aß. Our findings are evaluated and confirmed with multi-microsecond MD simulations. Finally, it is suggested that our proposed pipeline, with low computational cost in comparison with MD simulations, is a suitable approach for the virtual screening of ligand libraries against Aß.

Individual Differences in Growth and in Accumulation of Secondary Metabolites in Rhodiola rosea Cultivated in Western Siberia.

In this study, growth parameters of underground parts and concentrations of phenylpropanoids, phenylethanoids, flavonoids, hydroxybenzoic acids, and catechins in aqueous-ethanol extracts of 6-year-old cultivated plants of Rhodiola rosea (propagated in vitro) of Altai Mountain origin were analyzed, and differences in chemical composition among plant specimens and between plant parts (rhizome and root) were evaluated. High-performance liquid chromatography detected 13 phenolic compounds. Roots contained 1.28 times higher phenylethanoids levels (1273.72 mg/100 g) than rhizomes did. Overall, the concentration of phenylethanoids in underground organs was not high and ranged from 21.36 to 103.00 mg/100 g. High variation among R. rosea individual plants was noted both in growth characteristics and in levels of secondary metabolites under our cultivation conditions. It was found that concentrations of phenylpropanoids, phenylethanoids, and catechins significantly depend on the plant part analyzed (p ≤ 0.05). Specimen No. 4 is characterized by the highest concentration of rosavins (1230.99 mg/plant) and the lowest concentration of cinnamyl alcohol (62.87 mg/plant). Despite the wide range of values, all 10 tested specimens (underground part) met the minimum requirements of the United States Pharmacopeia (2015) for rosavins (0.3%) and of the Russia State Pharmacopoeia (2015) for the average level of rosavins (roots): (1%).