Epigallocatechin Gallate Molecules Research Articles

Biocompatible and nondegradable microcapsules using an ethylamine-bridged EGCG dimer for successful therapeutic cell transplantation

Conventional alginate microcapsules are widely used for encapsulating therapeutic cells to reduce the host immune response. However, the exchange of monovalent cations with divalent cations for crosslinking can lead to a sol-gel phase transition, resulting in gradual degradation and swelling of the microcapsules in the body. To address this limitation, we present a biocompatible and nondegradable epigallocatechin-3-gallate (EGCG)-based microencapsulation with ethylamine-bridged EGCG dimers (EGCG(d)), denoted as ‘Epi-Capsules’. These Epi-Capsules showed increased physical properties and Ca2+ chelating resistance compared to conventional alginate microcapsules. Horseradish peroxidase (HRP) treatment is very effective in increasing the stability of Epi-Capsule((+)HRP) due to the crosslinking between EGCG(d) molecules. Interestingly, the Epi-Capsules(oxi) using a pre-oxidized EGCG(d) can support long-term survival (>90 days) of xenotransplanted insulin-secreting islets in diabetic mice in vivo, which is attributed to its structural stability and reactive oxygen species (ROS) scavenging for lower fibrotic activity. Collectively, this EGCG-based microencapsulation can create Ca2+ chelating-resistance and anti-oxidant activity, which could be a promising strategy for cell therapies for diabetes and other diseases.

Self-Assembly of Cysteine into Nanofibrils Precedes Cystine Crystal Formation: Implications for Aggregation Inhibition.

The self-association of metabolites into well-ordered assemblies at the nanoscale has significant biological and medical implications. The thiol-containing amino acid cysteine (CYS) can assemble into amyloid-like nanofibrils, and its oxidized form, the disulfide-bonded cystine (CTE), forms hexagonal crystals as those found in cystinuria due to metabolic disorder. Yet, there have been no attempts to connect these two phenomena, especially the fibril-to-crystal transition. Here, we reveal that these are not separated events, and the CYS-forming amyloid fibrils are mechanistically linked to hexagonal CTE crystals. For the first time, we demonstrated that cysteine fibrils are a prerequisite for forming cystine crystals, as observed experimentally. To further understand this mechanism, we studied the effects of thiol-containing cystinuria drugs (tiopronin, TIO; and d-penicillamine, PEN) and the canonical epigallocatechin gallate (EGCG) amyloid inhibitor on fibril formation by CYS. The thiol-containing drugs do not solely interact with monomeric CYS via disulfide bond formation but can disrupt amyloid formation by targeting CYS oligomers. On the other hand, EGCG forms inhibitor-dominant complexes (more than one EGCG molecule per cysteine unit) to prevent CYS fibril formation. Interestingly, while CYS can be oxidized into CTE, the thiol drugs can reduce CTE back to CYS. We thus suggest that the formation of crystals in cystinuria could be halted at the initial stage by targeting CYS fibril formation as an alternative to solubilizing the water-insoluble hexagonal CTE crystals at a later stage. Taken together, we depicted a complex hierarchical organization in a simple amino acid assembly with implications for therapeutic intervention.

Ethanol-mediated synthesis of γ-cyclodextrin-based metal-organic framework as edible microcarrier: performance and mechanism

Here, an ethanol-mediated method was introduced to fabricate γ-cyclodextrin-based metal–organic frameworks (γ-CD-MOFs) as microcarriers for epigallocatechin-3-gallate (EGCG). Through adjusting ethanol gas diffusion temperature and ethanol liquid feed speed, we achieved control of crystallization efficiency and crystals size without extra surfactants. Under the sequential regulatory by ethanol in two phases, the obtained γ-CD-MOFs with cubic shape exhibited excellent crystallinity, high surface area, and uniform size distribution. Through the interplay of hydrogen bonding, hydrophobic interactions and π stacking, EGCG molecules could be stored efficiently within cavities and tunnels of the γ-CD-MOFs with high load capability of 334 mg g−1. More importantly, the incorporation of EGCG within frameworks wouldn’t disintegrate the unique body-centered cubic structure of γ-CD-MOFs, in turn, would improve the thermostability and antioxidative activity of EGCG. Significantly, all food-grade materials ensured the γ-CD-MOFs high acceptance and applicability for food and biomedical applications.

Development and characteristics of layered EGCG/Montmorillonite hybrid: An oral controlled-release formulation of EGCG

An oral controlled-release formulation of epigallocatechin-3-gallate (EGCG) was developed by intercalating EGCG into the interlayer space of Food and Drug Administration-approved mucoadhesive montmorillonite (Mt) nanolayers, and characterized by ultraviolet–visible, X-ray diffraction, Fourier transform infrared, and thermogravimetry. The EGCG intercalation was only possible at acidic pH, and occurred through electrostatic and hydrogen bonding interactions allowing restacking of exfoliated Mt nanolayers with EGCG molecules. It was inferred that EGCG molecules were adsorbed flat on the interlayer surface of Mt in a monolayer and formed two-sided hydrogen bonds with the Mt faces, leading to a ∼2-fold increase in the EGCG decomposition temperature. A maximum EGCG loading of ∼40 wt% was achieved at pH 3, reaction time 1 h, and EGCG:Mt ratio 40:10 mg/mL. The EGCG/Mt hybrid showed a sustained release of EGCG in simulated gastric and intestinal fluids in a pH-dependent manner. Deprotonation of EGCG was responsible for further EGCG release at pH 7.4 compared to pH 1.2. The release profiles were fitted to the parabolic diffusion and Bhaskar models, implying that the release was controlled by a diffusion process. These results suggest that Mt with a high loading capacity can be used as the controlled-release nanocarrier of EGCG in oral administration.

Epigallocatechin gallate: Phytochemistry, bioavailability, utilization challenges, and strategies.

Epigallocatechin gallate (EGCG), a green tea catechin, has gained the attention of current study due to its excellent health-promoting effects. It possesses anti-obesity, antimicrobial, anticancer, anti-inflammatory activities, and is under extensive investigation in functional foods for improvement. It is susceptible to lower stability, lesser bioavailability, and lower absorption rate due to various environmental, processing, formulations, and gastrointestinal conditions of the human body. Therefore, it is the foremost concern for the researchers to enhance its bioactivity and make it the most suitable therapeutic compound for its clinical applications. In the current review, factors affecting the bioavailability of EGCG and the possible strategies to overcome these issues are reviewed and discussed. This review summarizes structural modifications and delivery through nanoparticle-based approaches including nano-emulsions, encapsulations, and silica-based nanoparticles for effective use of EGCG in functional foods. Moreover, recent advances to enhance EGCG therapeutic efficacy by specifically targeting its molecules to increase its bioavailability and stability are also described. PRACTICAL APPLICATIONS: The main green tea constituent EGCG possesses several health-promoting effects making EGCG a potential therapeutic compound to cure ailments. However, its low stability and bioavailability render its uses in many disorders. Synthesizing EGCG prodrugs by structural modifications helps against its low bioavailability and stability by overcoming premature degradation and lower absorption rate. This review paper summarizes various strategies that benefit EGCG under different physiological conditions. The esterification, nanoparticle approaches, silica-based EGCG-NPs, and EGCG formulations serve as ideal EGCG modification strategies to deliver superior concentrations with lesser toxicity for its efficient penetration and absorption across cells both in vitro and in vivo. As a result of EGCG modifications, its bioactivities would be highly improved at lower doses. The protected or modified EGCG molecule would have enhanced potential effects and stability that would contribute to the clinical applications and expand its use in various food and cosmetic industries.

Green Tea Catechins: Role as Antiviral Agents

Green Tea Catechins (GTCs) - unarguably the wonder compounds with numerous medicinal properties and health benefits. And most importantly, these benefits include antiviral effects, so significant nowadays in our corona-hit world. The major catechins of green tea are four - epigallocatechin gallate (EGCG), epigallocatechin, epicatechin, and epicatechin-gallate. While each one of these has its own unique properties, EGCG, as per different studies, has been reported to be the most effective catechin showing significant antiviral activity against a broad spectrum of human and animal viruses. The antiviral properties of green tea extracts are manifold and target different areas. These include direct inactivation of the virus particles, prevention of entry into the target cell, inhibition of gene expression, inhibition of protein expression, inhibition of intestinal α-glycosidases that are important for processing glyco-conjugates of viruses, and lowering of proliferation of virus. Furtehrmore, a positive correlation between the antioxidant effects of catechins and their antiviral activities has been suggested. The growing concern about our health and the persistent fight while we are amidst the present coronavirus pandemic makes the inhibitory effect of GTCs a promising area of research. Due to their “relief and rectification” properties, these may be considered as a food supplement to ameliorate the harmful and deadly effects of the virus. The bioavailability of these polyphenols has been shown to be influenced by factors such as temperature, food processing methods, food matrix, and interaction with other compounds. Furthermore, the hydrophilic nature of EGCG molecule limits its bioavailability at the site of action. However, this limitation can be overcome and bioavailability of GTCs can be increased by chemical interventions, such as attachment of fatty acids. These ensure wide availability, and even wider use. The leading objective of this review is to collate, summarize and explain the information available on GTCs, and their effect on various pathogenic viruses in humans and animals. The GTCs surely promise to be an important weapon in our armour to fight corona and other pathogens.

Free radical grafting of whey protein isolate with tea polyphenol: Synthesis and changes in structural and functional properties

Free radical grafting is a green and expeditious tool that was used to modify whey protein isolate (WPI) to synthesize WPI-(−)-epigallocatechin-3-gallate (EGCG) and WPI-catechin (C) antioxidant emulsifier and improve its functional and interfacial properties. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF–MS) were used to verify the covalent bonding between polyphenols and WPI. Results revealed that at least two EGCG molecules and three catechin molecules were grafted onto WPI. Meanwhile, the grafting of tea polyphenols, especially EGCG, with WPI decreased their fluorescence intensity; α-helix content; and free amino, sulfhydryl, and tyrosine group contents. A lycopene nanoemulsion constructed with the WPI-EGCG conjugate had smaller changes in size and ζ-potential than that constructed with WPI during 30-day storage, which was attributed to its enhanced emulsifying activity, emulsification stability, and ability to reduce the interfacial tension of conjugates. The improvement in oxidation resistance and interfacial adsorption layer thickness helped the WPI-EGCG conjugate to significantly reduce the lycopene degradation rate during storage. Thus, WPI modified with polyphenol by free radical grafting can be used to construct an emulsion delivery system for functional nutrients with a stable interface and high retention rate.

Tea catechin as antiviral agent via apoptosis agonist and triple inhibitor mechanism against HIV-1 infection: A bioinformatics approach

Context: Human immunodeficiency virus (HIV) antiretrovirals that target the binding of viral enzyme are chosen as the lead solution in the treatment of HIV-1 infection, such as non-catalytic site integrase inhibitor (NCINI), nevirapine, and darunavir. There are natural compounds from specific plants that can be effective in treating HIV-1 infection such as tea catechin. Tea catechin administration causes a decrease in viral load and inhibition of entry mechanisms and an increased effect of apoptosis in infected cells. Aims: To identify the triple inhibitor mechanism in tea catechins against the three HIV-1 enzymes and apoptosis agonists through in silico approach as an innovation in handling HIV-1 infection. Methods: The 3D structure of tea catechin compounds from the database was examined, and then all target compounds were analyzed for drug-likeness, molecular docking, pathway prediction, and molecular interactions to determine the potential of tea catechin compounds as antiviral HIV-1 in silico. Results: Tea catechin compounds have the potential to serve as antiviral against HIV-1 through apoptosis agonist and triple inhibitor mechanisms. Apoptosis occurs due to the interaction of tea catechins with pro-apoptotic proteins in cells, and the epigallocatechin gallate (EGCG) compound is a class of tea catechins with the same binding position as control. Conclusions: The binding of the EGCG molecule complex results in low binding energy. Therefore, it allows EGCG acts as a triple inhibitor in HIV-1 infection.

How epigallocatechin gallate binds and assembles oligomeric forms of human alpha-synuclein

The intrinsically disordered human protein α-synuclein (αSN) can self-associate into oligomers and amyloid fibrils. Several lines of evidence suggest that oligomeric αSN is cytotoxic, making it important to devise strategies to either prevent oligomer formation and/or inhibit the ensuing toxicity. (−)-epigallocatechin gallate (EGCG) has emerged as a molecular modulator of αSN self-assembly, as it reduces the flexibility of the C-terminal region of αSN in the oligomer and inhibits the oligomer's ability to perturb phospholipid membranes and induce cell death. However, a detailed structural and kinetic characterization of this interaction is still lacking. Here, we use liquid-state NMR spectroscopy to investigate how EGCG interacts with monomeric and oligomeric forms of αSN. We find that EGCG can bind to all parts of monomeric αSN but exhibits highest affinity for the N-terminal region. Monomeric αSN binds ∼54 molecules of EGCG in total during oligomerization. Furthermore, kinetic data suggest that EGCG dimerization is coupled with the αSN association reaction. In contrast, preformed oligomers only bind ∼7 EGCG molecules per protomer, in agreement with the more compact nature of the oligomer compared with the natively unfolded monomer. In previously conducted cell assays, as little as 0.36 EGCG per αSN reduce oligomer toxicity by 50%. Our study thus demonstrates that αSN cytotoxicity can be inhibited by small molecules at concentrations at least an order of magnitude below full binding capacity. We speculate this is due to cooperative binding of protein-stabilized EGCG dimers, which in turn implies synergy between protein association and EGCG dimerization.

Molecular mechanisms of resveratrol and EGCG in the inhibition of Aβ42 aggregation and disruption of Aβ42 protofibril: similarities and differences.

The aggregation of amyloid-β protein (Aβ) into fibrillary deposits is implicated in Alzheimer's disease (AD), and inhibiting Aβ aggregation and clearing Aβ fibrils are considered as promising strategies to treat AD. It has been reported that resveratrol (RSV) and epigallocatechin-3-gallate (EGCG), two of the most extensively studied natural polyphenols, are able to inhibit Aβ fibrillization and remodel the preformed fibrillary aggregates into amorphous, non-toxic species. However, the mechanisms by which RSV inhibits Aβ42 aggregation and disrupts Aβ42 protofibril, as well as the inhibitory/disruptive mechanistic similarities and differences between RSV and EGCG, remain mostly elusive. Herein, we performed extensive all-atom molecular dynamics (MD) simulations on Aβ42 dimers (the early aggregation state of Aβ42) and protofibrils (the intermediate of Aβ42 fibril formation and elongation) in the absence/presence of RSV or EGCG molecules. Our simulations show that both RSV and EGCG can bind with Aβ42 monomers and inhibit the dimerization of Aβ42. The binding of RSV with Aβ42 peptide is mostly viaπ-π stacking interactions, while the binding of EGCG with Aβ42 is mainly through hydrophobic, π-π stacking, and hydrogen-bonding interactions. Moreover, both RSV and EGCG disrupt the β-sheet structure and K28-A42 salt bridges, leading to a disruption of Aβ42 protofibril structure. RSV mainly binds with residues whose side-chains point inwards from the surface of the protofibril, while EGCG mostly binds with residues whose side-chains point outwards from the surface of the protofibril. Furthermore, RSV interacts with Aβ42 protofibrils mostly viaπ-π stacking interactions, while EGCG interacts with Aβ42 protofibrils mainly via hydrogen-bonding and hydrophobic interactions. For comparison, we also explore the effects of RSV/EGCG molecules on the aggregation inhibition and protofibril disruption of the Iowa mutant (D23N) Aβ. Our findings may pave the way for the design of more effective drug candidates as well as the utilization of cocktail therapy using RSV and EGCG for the treatment of AD.

Coencapsulation and Stability Evaluation of Hydrophilic and Hydrophobic Bioactive Compounds in a Cagelike Phytoferritin.

Enrichment of multiple bioactive components with different characters into one food substrate simultaneously is a challenge. In this study, the hydrophilic epigallocatechin gallate (EGCG) and the hydrophobic quercetin were simultaneously enriched in the cavity of phytoferritin from red bean seed deprived of iron (apoRBF), a cagelike protein. The interactions of apoRBF with EGCG and quercetin were evaluated by UV/visible absorption, fluorescence, and circular dichroism technologies. By combination of the reversible assembly and urea induced approaches, both EGCG and quercetin were successfully coencapsulated in apoRBF to fabricate four kinds of apoRBF-EGCG-quercetin nanocomplexes FEQ (FEQ1, FEQ2, FEQ3, and FEQ4) with good solubility in aqueous solution. All FEQ samples maintained the typically spherical morphology of ferritin cage with a diameter around 12 nm. Among the four FEQ samples, the FEQ1 prepared by involving a pH 2.0/6.7 transition scheme was more effective in encapsulating EGCG and quercetin molecules than that by the urea induced method. Furthermore, all FEQs facilitated the stability of EGCG and quercetin molecules relative to free ones, and simultaneous coencapsulation of EGCG and quercetin could significantly improve the quercetin stability as compared with that of the free one and quercetin-loaded ferritin (p < 0.05), respectively. This work provides a new scheme to design and fabricate the ferritin based carrier for encapsulation of multiple bioactive components, and it is beneficial for the intensification of multifunction in one food substrate.

Evaluation of EGCG Loading Capacity in DMPC Membranes.

Catechins are molecules with potential use in different pathologies such as diabetes and cancer, but their pharmaceutical applications are often hindered by their instability in the bloodstream. This issue can be circumvented using liposomes as their nanocarriers for in vivo delivery. In this work, we studied the molecular details of (-)-epigallocatechin-3-gallate (EGCG) interacting with 1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC) monolayer/bilayer systems to understand the catechin loading ability and liposome stability, using experimental and computational techniques. The molecular dynamics simulations show the EGCG molecules deep inside the lipid bilayer, positioned below the lipid ester groups, generating a concentration-dependent lipid condensation. This effect was also inferred from the surface pressure isotherms of DMPC monolayers. In the polarization-modulated infrared reflection absorption spectra assays, the predominant effect at higher concentrations of EGCG (e.g., 20 mol %) was an increase in lipid tail disorder. The steady-state fluorescence data confirmed this disordered state, indicating that the catechin-induced liposome aggregation outweighs the condensation effects. Therefore, by adding more than 10 mol % EGCG to the liposomes, a destabilization of the vesicles occurs with the ensuing release of entrapped catechins. The loading capacity for DMPC seems to be limited by its disordered lipid arrangements, typical of a fluid phase. To further increase the clinical usefulness of liposomes, lipid bilayers with more stable and organized assemblies should be employed to avoid aggregation at large concentrations of catechin.

Dojeok-San, a traditional herbal formula, improves muscle atrophy from oxidative stress-induced skeletal muscle cells

Natural polyphenols, mainly found in tea, have many health benefits and have been used in traditional medicine for years; however, they have recently attracted a lot of attention in modern medicine. The present review discusses the therapeutic potential of Epigallocatechin gallate (EGCG) - its antioxidant and anticancer effects and health benefits, its structure and activity - by examining how the composition and arrangement of the molecule make it a suitable free radical scavenger, its pharmacokinetic parameters such as logP value and hydrogen bond donors and hydrogen bond acceptors and finally the main dilemma surrounding this drug molecule: its limited bioavailability - which leads to inconsistencies in its therapeutic potential. It also reviews and deliberates techniques to improve this molecule's efficacy, circumventing the obstacle of bioavailability by administering tea with different foods, administering EGCG as a double emulsion, or in the nanoparticulate form, or modifying the structure of the EGCG molecule.

Epigallocatechin-3-gallate location and interaction with late endosomal and plasma membrane model membranes by molecular dynamics

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea and it has been reported to have many beneficial properties against many different types of illnesses and infections. However, the exact mechanism/s underlying its biological effects are unknown. It has been previously shown that EGCG is capable of binding to and disrupting the membrane, so that some of its effects on biological systems could be ascribed to its capacity to incorporate into the biological membrane and modulate its structure. In this work, we have used atomistic molecular dynamics (MD) to discern the location and orientation of EGCG in model membranes and the possible existence of specific interactions with membrane lipids. For that goal, we have used in our simulation two complex model membranes, one resembling the plasma membrane (PM) and the other one the late endosome (LE) membrane. Our results support that EGCG tends to associate with the membrane and exists inside it in a relatively stable and steady location with a low propensity to be associated with other EGCG molecules. Interestingly, EGCG forms hydrogen bonds with POPC and POPE in the PM system but POPC and BMP and no POPE in the LE. These data suggest that the broad beneficial effects of EGCG could be mediated, at least in part, through its membranotropic effects and therefore membrane functioning.Communicated by Ramaswamy H. Sarma

Protective effect of epigallocatechin gallate on human erythrocytes.

The interactions and the protective effect of epigallocatechin gallate (EGCG) on human erythrocytes (RBC) and molecular models of its membrane were investigated. The latter consisted of bilayers built- up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. X-ray diffraction and differential scanning calorimetry experiments showed that EGCG induced significant structural and thermotropic perturbations in multilayers and vesicles of DMPC; however, these effects were not observed in DMPE. Fluorescence spectroscopy results revealed that EGCG produced alterations of the molecular dynamics at the level of the hydrophobic-hydrophilic interface in DMPC vesicles, and in isolated unsealed human erythrocyte membranes (IUM). EGCG also induced morphological alterations in RBC from their normal discoid form to echinocytes. These outcomes indicate that EGCG molecules were located in the outer monolayer of the erythrocyte membrane. The assessment of EGCG protective effect demonstrated that it inhibits the morphological alterations and lysis induced by HClO to human erythrocytes. The results obtained from this study suggest that the insertion of EGCG into the outer monolayer of the erythrocyte membrane might prevent the access and deleterious effects of oxidant molecules such as HClO and free radicals into the red cells, protecting them from oxidative damage.

Liposomal Formulations for an Efficient Encapsulation of Epigallocatechin-3-gallate: An in- Silico/Experimental Approach.

As a part of research project aimed to optimize antioxidant delivery, here we studied the influence of both salts and lipid matrix composition on the interaction of epigallocatechin-3-gallate (EGCG) with bilayer leaflets. Thus, we combined in silico and experimental methods to study the ability of neutral and anionic vesicles to encapsulate EGCG in the presence of Ca2+ and Mg2+ divalent salts. Experimental and in silico results show a very high correlation, thus confirming the efficiency of the developed methodology. In particular, we found out that the presence of calcium ions hinders the insertion of EGCG in the liposome bilayer in both neutral and anionic systems. On the contrary, the presence of MgCl2 improves the insertion degree of EGCG molecules respect to the liposomes without divalent salts. The best and most efficient salt concentration is that corresponding to a 5:1 molar ratio between Mg2+ and EGCG, in both neutral and anionic vesicles. Concerning the lipid matrix composition, the anionic one results in better promotion of the catechin insertion within the bilayer since experimentally we achieved 100% EGCG encapsulation in the lipid carrier in the presence of a 5:1 molar ratio of magnesium. Thus, the combination of this anionic liposomal formulation with magnesium chloride, avoids time-consuming separation steps of unentrapped active principle and appears particularly suitable for EGCG delivery applications.

Epigallocatechin gallate (EGCG) activity against UV light-induced photo damages in erythrocytes and serum albumin—theoretical and experimental studies

Ultraviolet (UV) exerts significant toxic effects on such blood components as erythrocytes and serum albumin under the influence of sunlight, during phototherapy, photodynamic therapy and pathogen reduction technology. In this study, we showed that epigallocatechin gallate (EGCG) isolated from Geranium rectum roots at concentrations of 1–20 μM protected erythrocytes against UVB induced damages, preventing ROS (reactive oxygen species) formation, lipid peroxidation (LP), reduced glutathione (GSH) and hemoglobin (Hb) oxidation. Our data on fluorescence anisotropy measurements noted that EGCG significantly increased the fluidity of the outer leaflet layer of erythrocytes membrane and induced a stiffening in the nonpolar region. We demonstrated that UVB irradiation of bovine serum albumin (BSA) induced SS disruption and SH group formation, which was prevented by EGCG in a dose-dependent manner. The analysis of radical-flavonoid interaction’s stoichiometry in the EGCG-DPPH model revealed that one EGCG molecule was consumed for reduction of two DPPH molecules. On the basis of theoretical calculation it was shown that the hydroxyl groups in positions 4′ and 5′ of the ring B could be considered as the most preferable H-atoms donators. Thus, the theoretical and experimental data showed that EGCG can be useful in protection of blood components against oxidative damages induced by UVB.

Epigallocatechin gallate, an active green tea compound inhibits the Zika virus entry into host cells via binding the envelope protein

Emerging infections of Zika virus (ZIKV) are associated with serious consequences like microcephaly and Guillain-Barré syndrome. It leads to a situation of global health emergency and demand an intensive research investigation to develop safe and effective therapeutics. Various efforts have been made to reduce the pathological pressure of ZIKV, but no effective drug has been introduced against ZIKV infections. A recent study has reported the inhibition of ZIKV entry into the host cells by an active green tea ingredient, Epigallocatechin Gallate (EGCG) in Vero E6cells. The effect of EGCG seems remarkable but lacking the information of the mechanism of action. In this study, we have investigated the binding site (Site1) of EGCG on envelope protein and provided the insights into various interactions of molecule with the binding site using molecular docking studies. Further, using molecular dynamics approaches we proposed the possible associated mechanism of inhibition of ZIKV entry by EGCG molecule. EGCG has found to interact with several residues and providing stability to the protein conformations up to 50ns simulations.

Salts Influence Cathechins and Flavonoids Encapsulation in Liposomes: A Molecular Dynamics Investigation.

Cathechins and flavonoids are responsible of numerous health benefits. Two of the most representatives' compounds for their antioxidant and therapeutic effects are Epigallocatechin 3-Gallate (EGCG), from green tea extracts, and morelloflavone (MF), from Garcinia dulcis. Here we explore, by atomistic Molecular Dynamics simulations, how EGCG and MF interact with lipid bilayers and we show the salts' influence on their encapsulation degree in neutral liposomes. As a result, we found out that EGCGs naturally bind to the hydrophilic regions of phospholipids, positioning themselves mostly at the interface between water and lipid phases. The presence of a salt clearly influences the EGCG molecules' absorption and the total effect depends strongly on the salt nature and concentration. Beside, for MF, we observed a high stability of the intermolecular MFs aggregates in water that strongly penalizes the flavonoid's interaction with the lipid polar heads. However, salts can influence MF's liposomal penetration, even if they are not able to promote completely its absorption inside the bilayer. For both compounds, the increase of penetration is more marked in presence of magnesium chloride, whilst calcium chloride showed the opposite effect.

Drug-tea polyphenol interaction (II) complexation of piperazine derivatives with green tea polyphenol

Complex formation between piperazine derivatives (PD) and green tea polyphenols (GTP) in an aqueous solutions and the mechanism were studied by isothermal titration microcalorimetry and molecular modeling study. Lomerizine dihydrochloride (LMZ), cetirizine dihydrochloride (CTZ) and hydroxyzine dihydrochloride (HXZ) were used as PD, and (−)-epigallocatechin gallate (EGCg) and (−)-epigallocatechin (EGC) were used as GTP. The mixed solutions of PD (except HXZ) and EGCg were cloudy because an insoluble complex was formed, and PD remaining in the solutions were approximately 30–60%. LMZ and CTZ formed complexes with EGCg at a 2:1 molar ratio, and the thermodynamic parmeters were ΔG=−23.9kJmol−1, ΔH=−22.6kJmol−1 and TΔS=1.3kJmol−1 for the LMZ-EGCg system and ΔG=−23.0kJmol−1, ΔH=−21.5kJmol−1 and TΔS=1.5kJmol−1 for the CTZ-EGCg system. The mixed solution of HXZ and EGCg was not cloudy, and approximately 100% of HXZ remained in the solution. On the other hand, the residual rate of PD in the solution did not decrease after mixing with EGC. No heat of the reaction was observed in HXZ-EGCg and PD-EGC systems. It was clarified that hydrogen bond formation between the nitrogen atom of the piperazine ring in a molecule of PD and the hydroxyl group of galloyl ring of an EGCg molecule played an important role in stabilization of the complexes.