Theaflavin-3,3'-digallate effectively attenuates biofilm formation by Enterococcus faecalis via the targeting of specific quorum sensing pathways.

Enterococcus faecalis, an opportunistic pathogen responsible for nosocomial infections, exhibits increased pathogenicity via biofilm formation. Theaflavin-3,3'-digallate (TF3), a theaflavin extracted from black tea, exhibits potent antibacterial effects. In the present study, we investigated the inhibitory effect of TF3 on E. faecalis. Our results indicated that TF3 significantly inhibited E. faecalis ATCC 29212 biofilm formation. This observation was further confirmed via crystal violet staining, confocal laser scanning microscopy, and field emission-scanning electron microscopy. To disclose the underlying mechanisms, RNA-seq was applied. TF3 treatment significantly altered the transcriptomic profile of E. faecalis, as evidenced by identification of 248 differentially expressed genes (DEGs). Through functional annotation of these DEGs, several quorum-sensing pathways were found to be suppressed in TF3-treated cultures. Further, gene expression verification via real-time PCR confirmed the downregulation of gelE, sprE, and secY by TF3. These findings highlighted the ability of TF3 to impede E. faecalis biofilm formation, suggesting a novel preventive strategy against E. faecalis infections.

Construction of recombinant fluorescent LSDV for high-throughput screening of antiviral drugs.

Lumpy skin disease virus (LSDV) infection is a major socio-economic issue that seriously threatens the global cattle-farming industry. Here, a recombinant virus LSDV-ΔTK/EGFP, expressing enhanced green fluorescent protein (EGFP), was constructed with a homologous recombination system and applied to the high-throughput screening of antiviral drugs. LSDV-ΔTK/EGFP replicates in various kidney cell lines, consistent with wild-type LSDV. The cytopathic effect, viral particle morphology, and growth performance of LSDV-ΔTK/EGFP are consistent with those of wild-type LSDV. High-throughput screening allowed to identify several molecules that inhibit LSDV-ΔTK/EGFP replication. The strong inhibitory effect of theaflavin on LSDV was identified when 100 antiviral drugs were screened in vitro. An infection time analysis showed that theaflavin plays a role in the entry of LSDV into cells and in subsequent viral replication stages. The development of this recombinant virus will contribute to the development of LSDV-directed antiviral drugs and the study of viral replication and mechanisms of action.

Antiviral activity of theaflavins against Zika virus in vivo and in vitro.

INTRODUCTION: The prevalence and infection of the Zika virus (ZIKV) have recently posed a major threat to global public health security. However, there is currently a lack of specific vaccines and effective antiviral drugs for ZIKV infection. METHODS: Theaflavins TF1 and TF2 were selected by evaluating the anti-Zika virus activity of four kinds of theaflavins in vitro. Subsequently, in vivo, we investigated the effects of TF1 and TF2 on weight, survival, tissue viral load, and cytokines in ZIKV-infected mice. RESULTS: We compared the anti-ZIKV activity of four theaflavins (TFs) in cells and found that TF1 and TF2b significantly inhibited the replication of ZIKV/Z16006 toxic strain in BHK and Vero cells by inhibiting the replication and release of ZIKV, while no similar effects were observed for TF2a and TF3. In vivo assay, we only found that TF2b improved the survival rate of infected mice. In tissues of ZIKV-infected mice, the viral load was higher in spleen and blood, followed by liver, epididymis, and testis, the lowest in muscle. Additionally, TF2b treatment significantly reduced the expression of cytokines (IL-6, IL-1ß, TNF-α) and chemokines (CCL2, CCL5, CXCL10) induced by ZIKV infection. CONCLUSIONS: These findings suggest that TF2b has a potent antiviral effect and can be used as a potential candidate for the treatment of ZIKV infection.

The Inhibiting Effect of GB-2, (+)-Catechin, Theaflavin, and Theaflavin 3-Gallate on Interaction between ACE2 and SARS-CoV-2 EG.5.1 and HV.1 Variants.

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, continues to pose significant global health challenges. The results demonstrated that GB-2 at 200 µg/mL effectively increased the population of 293T-ACE2 cells with low RBD binding for both SARS-CoV-2 Omicron EG.5.1 and HV.1 variants by dual-color flow cytometry, indicating its ability to inhibit virus attachment. Further investigation revealed that (+)-catechin at 25 and 50 µg/mL did not significantly alter the ACE2-RBD interaction for the EG.5.1 variant. In contrast, theaflavin showed inhibitory effects at both 25 and 50 µg/mL for EG.5.1, while only the higher concentration was effective for HV.1. Notably, theaflavin 3-gallate exhibited a potent inhibition of ACE2-RBD binding for both variants at both concentrations tested. Molecular docking studies provided insight into the binding mechanisms of theaflavin and theaflavin 3-gallate with the RBD of EG.5.1 and HV.1 variants. Both compounds showed favorable docking scores, with theaflavin 3-gallate demonstrating slightly lower scores (-8 kcal/mol) compared to theaflavin (-7 kcal/mol) for both variants. These results suggest stable interactions between the compounds and key residues in the RBD, potentially explaining their inhibitory effects on virus attachment. In conclusion, GB-2, theaflavin, and theaflavin 3-gallate demonstrate significant potential as inhibitors of the ACE2-RBD interaction in Omicron variants, highlighting their therapeutic promise against COVID-19. However, these findings are primarily based on computational and in vitro studies, necessitating further in vivo research and clinical trials to confirm their efficacy and safety in humans.

Theaflavin mitigates acute gouty peritonitis and septic organ injury in mice by suppressing NLRP3 inflammasome assembly.

Activation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome plays important role in defending against infections, but its aberrant activation is causally linked to many inflammatory diseases, thus being a therapeutic target for these diseases. Theaflavin, one major ingredient of black tea, exhibits potent anti-inflammatory and anti-oxidative activities. In this study, we investigated the therapeutic effects of theaflavin against NLRP3 inflammasome activation in macrophages in vitro and in animal models of related diseases. We showed that theaflavin (50, 100, 200 µM) dose-dependently inhibited NLRP3 inflammasome activation in LPS-primed macrophages stimulated with ATP, nigericin or monosodium urate crystals (MSU), evidenced by reduced release of caspase-1p10 and mature interleukin-1ß (IL-1ß). Theaflavin treatment also inhibited pyroptosis as shown by decreased generation of N-terminal fragment of gasdermin D (GSDMD-NT) and propidium iodide incorporation. Consistent with these, theaflavin treatment suppressed ASC speck formation and oligomerization in macrophages stimulated with ATP or nigericin, suggesting reduced inflammasome assembly. We revealed that theaflavin-induced inhibition on NLRP3 inflammasome assembly and pyroptosis resulted from ameliorated mitochondrial dysfunction and reduced mitochondrial ROS production, thereby suppressing interaction between NLRP3 and NEK7 downstream of ROS. Moreover, we showed that oral administration of theaflavin significantly attenuated MSU-induced mouse peritonitis and improved the survival of mice with bacterial sepsis. Consistently, theaflavin administration significantly reduced serum levels of inflammatory cytokines including IL-1ß and attenuated liver inflammation and renal injury of mice with sepsis, concomitant with reduced generation of caspase-1p10 and GSDMD-NT in the liver and kidney. Together, we demonstrate that theaflavin suppresses NLRP3 inflammasome activation and pyroptosis by protecting mitochondrial function, thus mitigating acute gouty peritonitis and bacterial sepsis in mice, highlighting a potential application in treating NLRP3 inflammasome-related diseases.

CXCR4 as possible druggable target linking inflammatory bowel disease and Parkinson's disease.

Parkinson's disease (PD) is a chronic, progressive, and second most prevalent neurological disorder affecting the motor system. It has been found that people suffering with inflammatory bowel disease (IBD) are at 22% more risk for PD. In the current study, we have established a molecular link between gut and brain. The microarray gene expression datasets of Homo sapiens were obtained from Gene Expression Omnibus Database. Major genes involved in gut-brain connection were found to be CXCR4, LRRK2, APOE, SNCA, IL6, HIF-1α, ABCA1 etc. The common biological pathways linking both the pathologies were found to be HIF-signaling, cytokines interactions, JAK-STAT pathway, cholesterol metabolism, apoptosis and CXCR4 signaling which modulates the synaptic function and neuronal survival in the mature brain. It is known that flavonoid-rich foods throughout life hold the potential to limit the inflammation, neurodegeneration and, to prevent the age-dependent cognitive impairment. Therefore, the potential receptor, CXCR4 was used further for docking with twenty-seven phytochemicals from 5 different classes of Flavonoids found in several dietary items. Docking studies of the top scoring compounds were compared with a known inhibitor (BPRCX807) of receptor CXCR4 (IC50 = 40.4 ± 8.0 nM). The study indicates that Flavan-3-ol families of flavonoids are the best fit and finest dietary supplements for improving brain health. Hence the food items like Pistachio nuts, hazelnuts, Green Tea, walnuts, etc. should be incorporated more in the diet of healthy people as well as in IBD and PD patients to prevent inflammation in gut and brain damage from oxidative stress.

Theaflavin Ameliorates Streptococcus suis-Induced Infection In Vitro and In Vivo.

Streptococcus suis (S. suis) is one of the most important zoonotic pathogens that threaten the lives of pigs and humans. Even worse, the increasingly severe antimicrobial resistance in S. suis is becoming a global issue. Therefore, there is an urgent need to discover novel antibacterial alternatives for the treatment of S. suis infection. In this study, we investigated theaflavin (TF1), a benzoaphenone compound extracted from black tea, as a potential phytochemical compound against S. suis. TF1 at MIC showed significant inhibitory effects on S. suis growth, hemolytic activity, and biofilm formation, and caused damage to S. suis cells in vitro. TF1 had no cytotoxicity and decreased adherent activity of S. suis to the epithelial cell Nptr. Furthermore, TF1 not only improved the survival rate of S. suis-infected mice but also reduced the bacterial load and the production of IL-6 and TNF-α. A hemolysis test revealed the direct interaction between TF1 and Sly, while molecular docking showed TF1 had a good binding activity with the Glu198, Lys190, Asp111, and Ser374 of Sly. Moreover, virulence-related genes were downregulated in the TF1-treated group. Collectively, our findings suggested that TF1 can be used as a potential inhibitor for treating S. suis infection in view of its antibacterial and antihemolytic activity.

Improving Theaflavin-3,3'-digallate Production Efficiency Optimization by Transition State Conformation of Polyphenol Oxidase.

Theaflavins (TFs) are good for health because of their bioactivities. Enzymatic synthesis of TFs has garnered much attention; however, the source and activity of the enzymes needed limit their wide application. In this study, a microbial polyphenol oxidase from Bacillus megaterium was screened for the synthesis of theaflavin-3,3'-digallate (TFDG). Based on structural and mechanistic analyses of the enzyme, the O-O bond dissociation was identified as the rate-determining step. To address this issue, a transition state (TS) conformation optimization strategy was adopted to stabilize the spatial conformation of the O-O bond dissociation, which improved the catalytic efficiency of tyrosinase. Under the optimum transformation conditions of pH 4.0, temperature 25 °C, (-)-epigallocatechin gallate/epicatechin gallate molar ratio of 2:1, and time of 30 min, Mu4 (BmTyrV218A/R209S) produced 960.36 mg/L TFDG with a 44.22% conversion rate, which was 6.35-fold higher than that of the wild type. Thus, the method established has great potential in the synthesis of TFDG and other TFs.

Effect of theaflavins on the quality of large yellow croaker (Larimichthys crocea) during refrigerated storage.

BACKGROUND: Large yellow croaker (Larimichthys crocea) is an economical marine fish consumed in China. Theaflavins have antibacterial and antioxidant properties. However, there is a lack of research into their application in large yellow croakers during refrigerated storage. This study investigated the effect of theaflavins on the quality of large yellow croaker (Larimichthys crocea) during 12 days of storage at 4 °C. RESULTS: The results showed that theaflavin treatment was able to inhibit microbial growth and reduce the production of total volatile basic nitrogen (TVB-N). Meanwhile, theaflavins were beneficial in reducing the unfolding of myofibrillar proteins, decreasing the degree of protein aggregation, and improving the stability of protein structure. The degree of protein oxidation was lower in a theaflavin-treated group compared with an untreated group. Theaflavin treatment effectively inhibited increases in acid value (AV), peroxide value (PV), and malonaldehyde (MDA) content. The effect of theaflavin was positively correlated with an increase in concentration under refrigeration conditions. This study therefore suggests that the use of theaflavins is a viable method for extending the period for which refrigerated large yellow croaker can be preserved. CONCLUSIONS: Adding theaflavins to large yellow croaker can be an effective method for preserving quality during refrigerated storage. © 2023 Society of Chemical Industry.

Theaflavin binds to a druggable pocket of TMEM16A channel and inhibits lung adenocarcinoma cell viability.

As a calcium-activated chloride channel regulated by the intracellular Ca2+ concentration and membrane potential, TMEM16A has attracted considerable attention and has been proposed as a novel anticancer drug target. We have previously reported that the pocket above the ion conductance pore could be a nonselective inhibitor-binding pocket. However, whether this pocket is druggable remains unexplored. In this study, we performed virtual screening to target the presumed inhibitor-binding pocket and identified a highly effective TMEM16A inhibitor, theaflavin (TF: a tea polyphenol in black tea). Molecular dynamics simulations revealed that theaflavin adopts a "wedge insertion mode" to block the ion conduction pore and induces pore closure. Moreover, the binding mode showed that the TF pedestal plays an important role in pore blockade, and R515, R535, T539, K603, E623, and E633 were determined to be most likely to interact directly with the pedestal. Mutagenesis experiment results corroborated the mechanism through which TF binds to this pocket. Combined with the quantitative calculation results, our data indicated that the three hydroxyl groups on the pedestal may be the most crucial pharmacophores for TMEM16A inhibition by TF. Finally, antitumor experiments revealed that TF could target TMEM16A to inhibit the proliferation and migration of LA795 cells, indicating the potential therapeutic effect of TF on the growth of lung adenocarcinoma with high TMEM16A expression. The successful application of drug screening strategies based on this binding pocket highlights new directions for discovering superior modulators and contributes to the development of novel therapeutics for lung adenocarcinoma.

Flexion of Nrf2 by tea phytochemicals: A review on the chemopreventive and chemotherapeutic implications.

Nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2), the redox-sensitive transcription factor, plays a key role in stress-defense and detoxification. Nrf2 is tightly controlled by its negative regulator cum sensor Kelch-[ECH]-associated protein 1 (Keap1). Nrf2 is well known for its dual nature owing to its cancer preventive and cancer promoting abilities. Modulation of this biphasic nature of Nrf2 signaling by phytochemicals may be a potential cancer preventive and anticancer therapeutic strategy. Phytocompounds may either act as Nrf2-activator or Nrf2-inhibitor depending on their differential concentration and varied cellular environment. Tea is not just the most popular global beverage with innumerable health-benefits but has well-established chemopreventive and chemotherapeutic effects. Various types of tea infusions contain a wide range of bioactive compounds, such as polyphenolic catechins and flavonols, which are endowed with potent antioxidant properties. Despite of their rapid biotransformation and poor bioavailability, regular tea consumption is risk-reductive for several cancer forms. Tea catechins show their dual Nrf2-modulatory effect by directly acting on Nrf2-Keap1 or their upstream regulators and downstream effectors in a highly case-specific manner. In this review, we have tried to present a comprehensive evaluation of the Nrf2-mediated chemopreventive and chemotherapeutic applications of tea in various preclinical cancer models, the Nrf2-modulatory mechanisms, and the limitations which need to be addressed in future research.

Theaflavin and its derivatives exert antibacterial action against Bacillus coagulans through adsorption to cell surface phospholipids.

AIMS: To investigate the antibacterial effects of tea theaflavins and catechins against Bacillus coagulans and the underlying mechanism of antibacterial action. METHODS AND RESULTS: Bactericidal activities of theaflavin and its analogues were evaluated and compared with that of epigallocatechin gallate. Theaflavin derivatives exhibited high bactericidal activity at 50 µmol L-1 , whereas epigallocatechin gallate did not, even at 500 µmol L-1 . Furthermore, we investigated the adsorption of theaflavins to model phospholipid membranes and corresponding effects on membrane fluidity to reveal their effects on the B. coagulans cell surface. Cell membrane fluidity was decreased after treatment with theaflavin derivatives with one or more galloyl moieties. Quartz-crystal microbalance analysis showed a strong affinity of the membrane phosphatidyl glycerol (PG) bilayers for theaflavin derivatives, correlating their bactericidal activity. CONCLUSION: These findings suggest that theaflavins could effectively inhibit B. coagulans by decreasing cell membrane fluidity. SIGNIFICANCE AND IMPACT: Bacillus coagulans is a spore-forming heat-resistant bacterium responsible for spoilage in low-acidic beverages. Natural antimicrobial components in tea-based beverages are central to reducing microbial contamination and product quality deterioration, although mechanisms underlying their antimicrobial action remain obscure. This study highlights the inhibitory action of theaflavins on B. coagulans and their potential application in food and beverage industries.

Evaluation of antityrosinase activity and mechanism, antioxidation, and UV filter properties of theaflavin.

Tyrosinase is a key metalloenzyme for the biosynthesis of melanin that plays a critical role in the prevention of skin damage caused by ultraviolet (UV) radiation. However, the overproduction of melanin may cause a variety of skin diseases. Due to the toxicity and inefficiency of existing tyrosinase inhibitors, it is urgent to identify safe and potent alternatives from natural sources. Theaflavin, a single-component extracted from black tea, has been found to possess a variety of pharmacological activities. Herein, the inhibition kinetics of theaflavin on tyrosinase and inhibitory mechanism were determined using spectroscopy, molecular docking, and zebrafish model. The results showed that theaflavin inhibited the diphenolase activity of tyrosinase in a reversible mixed type manner with IC50 of 229.75 µmol/L and hindered the synthesis of melanin in zebrafish. This may be due to the formation of eight hydrogen bonds and hydrophobic effects between theaflavin and tyrosinase according to the results of molecular docking. To study the possible effects on the prevention of free radical-mediated skin cancer and photoaging caused by UV radiation, the antioxidation and UV filter properties of theaflavin were further verified. This study demonstrates that theaflavin is a potential multifunctional compound that can be used in cosmetic and medicinal products.

Antibacterial and Sporicidal Activity Evaluation of Theaflavin-3,3'-digallate.

Theaflavin-3,3'-digallate (TFDG), a polyphenol derived from the leaves of Camellia sinensis, is known to have many health benefits. In this study, the antibacterial effect of TFDG against nine bacteria and the sporicidal activities on spore-forming Bacillus spp. have been investigated. Microplate assay, colony-forming unit, BacTiter-GloTM, and Live/Dead Assays showed that 250 µg/mL TFDG was able to inhibit bacterial growth up to 99.97%, while 625 µg/mL TFDG was able to inhibit up to 99.92% of the spores from germinating after a one-hour treatment. Binding analysis revealed the favorable binding affinity of two germination-associated proteins, GPR and Lgt (GerF), to TFDG, ranging from -7.6 to -10.3 kcal/mol. Semi-quantitative RT-PCR showed that TFDG treatment lowered the expression of gpr, ranging from 0.20 to 0.39 compared to the control in both Bacillus spp. The results suggest that TFDG not only inhibits the growth of vegetative cells but also prevents the germination of bacterial spores. This report indicates that TFDG is a promising broad-spectrum antibacterial and anti-spore agent against Gram-positive, Gram-negative, acid-fast bacteria, and endospores. The potential anti-germination mechanism has also been elucidated.

New insights into the effect of fermentation temperature and duration on catechins conversion and formation of tea pigments and theasinensins in black tea.

BACKGROUND: The phenol oxidative pathway during fermentation remains unclear. To elucidate the effect of fermentation on phenol conversion, we investigated the effects of fermentation temperature and duration on the conversion of catechins and the formation of theasinensins (TSs), theaflavins (TFs), thearubigins (TRs), and theabrownins (TBs). RESULTS: During fermentation, TSs formation increased initially and then decreased. Long fermentation durations were unfavorable for liquor brightness (LB) and resulted in the production of large amounts of TRs and TBs. Low fermentation temperatures (20 °C and 25 °C) favored the maintenance of polyphenol oxidase activity and the continuous formation of TFs, TSs, and TRSI (a TRs fraction), resulting in better LB and liquor color. Higher temperatures (30 °C, 35 °C, and 40 °C) resulted in higher peroxidase activity, higher oxidative depletion rates of catechins, and excessive production of TRSII (a TRs fraction) and TBs. Analysis of the conversion pathway of polyphenolic compounds during fermentation showed that, during early fermentation, large amounts of catechins were oxidized and converted to TFs and theasinensin B. As fermentation progressed, considerable amounts of theaflavin-3'-gallate, theasinensin A, theaflavin-3-gallate, theaflavin-3,3'-digallate, and theasinensin C were produced and then converted to TRSI; in the final stage, TRSII and TBs were converted continuously. CONCLUSION: Different fermentation temperature and duration combinations directly affected the type and composition of phenolic compounds. The key conditions for controlling phenolic compound conversion and fermentation direction were 60 or 90 min and 25 or 30 °C. Our study provides insights into the regulation of phenolic compound conversion during black tea fermentation. © 2021 Society of Chemical Industry.

Significant Inactivation of SARS-CoV-2 In Vitro by a Green Tea Catechin, a Catechin-Derivative, and Black Tea Galloylated Theaflavins.

Potential effects of tea and its constituents on SARS-CoV-2 infection were assessed in vitro. Infectivity of SARS-CoV-2 was decreased to 1/100 to undetectable levels after a treatment with black tea, green tea, roasted green tea, or oolong tea for 1 min. An addition of (-) epigallocatechin gallate (EGCG) significantly inactivated SARS-CoV-2, while the same concentration of theasinensin A (TSA) and galloylated theaflavins including theaflavin 3,3'-di-O-gallate (TFDG) had more remarkable anti-viral activities. EGCG, TSA, and TFDG at 1 mM, 40 µM, and 60 µM, respectively, which are comparable to the concentrations of these compounds in tea beverages, significantly reduced infectivity of the virus, viral RNA replication in cells, and secondary virus production from the cells. EGCG, TSA, and TFDG significantly inhibited interaction between recombinant ACE2 and RBD of S protein. These results suggest potential usefulness of tea in prevention of person-to-person transmission of the novel coronavirus.

Severe Acute Respiratory Syndrome Coronavirus-2 Inactivation Activity of the Polyphenol-Rich Tea Leaf Extract with Concentrated Theaflavins and Other Virucidal Catechins.

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is producing a large number of infections and deaths globally, the development of supportive and auxiliary treatments is attracting increasing attention. Here, we evaluated SARS-CoV-2-inactivation activity of the polyphenol-rich tea leaf extract TY-1 containing concentrated theaflavins and other virucidal catechins. The TY-1 was mixed with SARS-CoV-2 solution, and its virucidal activity was evaluated. To evaluate the inhibition activity of TY-1 in SARS-CoV-2 infection, TY-1 was co-added with SARS-CoV-2 into cell culture media. After 1 h of incubation, the cell culture medium was replaced, and the cells were further incubated in the absence of TY-1. The viral titers were then evaluated. To evaluate the impacts of TY-1 on viral proteins and genome, TY-1-treated SARS-CoV-2 structural proteins and viral RNA were analyzed using western blotting and real-time RT-PCR, respectively. TY-1 showed time- and concentration-dependent virucidal activity. TY-1 inhibited SARS-CoV-2 infection of cells. The results of western blotting and real-time RT-PCR suggested that TY-1 induced structural change in the S2 subunit of the S protein and viral genome destruction, respectively. Our findings provided basic insights in vitro into the possible value of TY-1 as a virucidal agent, which could enhance the current SARS-CoV-2 control measures.

The potential chemical structure of anti-SARS-CoV-2 RNA-dependent RNA polymerase.

An outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan and it has rapidly spread to almost all parts of the world. For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an important polymerase that catalyzes the replication of RNA from RNA template and is an attractive therapeutic target. In this study, we screened these chemical structures from traditional Chinese medicinal compounds proven to show antiviral activity in severe acute respiratory syndrome coronavirus (SARS-CoV) and the similar chemical structures through a molecular docking study to target RdRp of SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS-CoV-2 (-9.11 kcal/mol), SARS-CoV (-8.03 kcal/mol), and MERS-CoV (-8.26 kcal/mol) from idock. To confirm the result, we discovered that theaflavin has lower binding energy of -8.8 kcal/mol when it docks in the catalytic pocket of SARS-CoV-2 RdRp by using the Blind Docking server. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp. Moreover, one π-cation interaction was formed between theaflavin and Arg553 from the Blind Docking server. Our results suggest that theaflavin could be a potential SARS-CoV-2 RdRp inhibitor for further study.

Production Mechanisms of Black Tea Polyphenols.

Black tea accounts for 70-80% of world tea production, and the polyphenols therein are produced by enzymatic oxidation of four tea catechins during tea fermentation. However, only limited groups of dimeric oxidation products, such as theaflavins, theasinensins, and theacitrins, have been isolated from black tea and chemically characterized. This is largely because of the complexity and heterogeneity of the oxidation products. To determine structures and production mechanisms of uncharacterized black tea polyphenols, in vitro model fermentation experiments using pure catechins and polyphenol oxidase have been applied, and basic oxidation mechanisms have been established. Contemporary methods, such as LC-MS, are also effective to identify catechin oxidation products in black tea. Despite ongoing efforts, almost 60% of the solids in black tea infusion remain uncharacterized. These compounds include the so-called thearubigins, which are a heterogeneous mixture of uncharacterized catechin oxidation products with oligomeric structures. This review summarizes the current knowledge of the production mechanisms of representative black tea polyphenols and presents recent progress in characterization of thearubigins.

Black tea polyphenol theaflavin as promising antioxidant and potential copper chelator.

BACKGROUND: In this work, we investigated the antioxidant and copper chelating abilities of theaflavin, a polyphenol responsible for astringency, color, and sensation in black tea. Using voltammetric techniques, the analyses were conducted with disposable electrochemical printed carbon chips in conjunction with a portable hand-held potentiostat. RESULTS: Voltammograms of theaflavin showed five separate oxidation peaks, corresponding to the oxidation of five individual functional groups. Electroanalytical data indicated that, after interaction with copper, theaflavin had higher antioxidant potential and was a better copper chelator than epigallocatechin gallate, a major polyphenol present in green tea and a well-known antioxidant. This could be attributed to the extra fused ring and larger number of OH groups in theaflavin. CONCLUSIONS: Our findings introduce another natural compound as a potential nutraceutical in oxidation- and copper-modulated illnesses. This simple and fast approach would also be highly pertinent to the inspection of the health benefits of natural food products. To the best of our knowledge, this is the first report of the electrochemical analysis of Cu (II) chelation with theaflavin. © 2020 Society of Chemical Industry.