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Green Tea Catechin-Inactivated Viral Vaccine Platform.

ABSTRACT: Traditionally, chemical agents such as formalin (FA) and β-propiolactone (BPL) have long been used for the preparation of inactivated vaccines or toxoids. It has been shown that FA extensively modifies vaccine antigens and thus affects immunogenicity profiles, sometimes compromising the protective efficacy of the vaccines or even exacerbating the disease upon infection. In this study, we show that natural catechins from green tea extracts (GT) can be used as an inactivating agent to prepare inactivated viral vaccines. GT treatment resulted in complete and irreversible inactivation of influenza virus as well as dengue virus. In contrast to FA that reacted extensively with multiple amino acids including lysine, a major anchor residue for epitope binding to MHC molecules, GT catechin epigallocatechin-3-gallate (EGCG) crosslinked primarily with cysteine residues and thus preserved the major epitopes of the influenza hemagglutinin. In a mouse model, vaccination with GT-inactivated influenza virus (GTi virus) elicited higher levels of viral neutralizing antibodies than FA-inactivated virus (FAi virus). The vaccination completely protected the mice from a lethal challenge and restricted the challenge viral replication in the lungs. Of note, the quality of antibody responses of GTi virus was superior to that with FAi virus, in terms of the magnitude of antibody titer, cross-reactivity to hetero-subtypes of influenza viruses, and the avidity to viral antigens. As the first report of using non-toxic natural compounds for the preparation of inactivated viral vaccines, the present results could be translated into a clinically relevant vaccine platform with improved efficacy, safety, productivity, and public acceptance.

SUBMITTER: Lee YH

PROVIDER: S-EPMC5732980 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The Green Tea Catechin Epigallocatechin Gallate Ameliorates Graft-versus-Host Disease.

Project description:Allogeneic hematopoetic stem cell transplantation (allo-HSCT) is a standard treatment for leukemia and other hematologic malignancies. The major complication of allo-HSCT is graft-versus-host-disease (GVHD), a progressive inflammatory illness characterized by donor immune cells attacking the organs of the recipient. Current GVHD prevention and treatment strategies use immune suppressive drugs and/or anti-T cell reagents these can lead to increased risk of infections and tumor relapse. Recent research demonstrated that epigallocatechin gallate (EGCG), a component found in green tea leaves at a level of 25-35% at dry weight, may be useful in the inhibition of GVHD due to its immune modulatory, anti-oxidative and anti-angiogenic capacities. In murine allo-HSCT recipients treated with EGCG, we found significantly reduced GVHD scores, reduced target organ GVHD and improved survival. EGCG treated allo-HSCT recipients had significantly higher numbers of regulatory T cells in GVHD target organs and in the blood. Furthermore, EGCG treatment resulted in diminished oxidative stress indicated by significant changes of glutathione blood levels as well as glutathione peroxidase in the colon. In summary, our study provides novel evidence demonstrating that EGCG ameliorates lethal GVHD and reduces GVHD-related target organ damage. Possible mechanisms are increased regulatory T cell numbers and reduced oxidative stress.

| S-EPMC5245838 | biostudies-literature

The green tea catechin epigallocatechin gallate inhibits SARS-CoV-2 infection.

Project description:The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and more than a million deaths. The infection causes COVID-19, a disease of the respiratory system of divergent severity. No treatment exists. Epigallocatechin-3-gallate (EGCG), the major component of green tea, has several beneficial properties, including antiviral activities. Therefore, we examined whether EGCG has antiviral activity against SARS-CoV-2. EGCG blocked not only the entry of SARS-CoV-2, but also MERS- and SARS-CoV pseudotyped lentiviral vectors and inhibited virus infections in vitro. Mechanistically, inhibition of the SARS-CoV-2 spike-receptor interaction was observed. Thus, EGCG might be suitable for use as a lead structure to develop more effective anti-COVID-19 drugs.

| S-EPMC8290267 | biostudies-literature

Applications of a Standardized Green Tea Catechin Preparation for Viral Warts and Human Papilloma Virus-Related and Unrelated Cancers.

Project description:Most cell-based and animal experiments have shown that green tea catechins (GTC) exhibit various health benefits. In human experimental and epidemiological studies, there are conflicting results, and more precise investigations are required. One of the most effective ways to prove beneficial health effects in humans might be clinical intervention studies. Polyphenon®E was developed as a standardized GTC preparation, which was approved by Food and Drug Administration of US in 2006 as a medication to treat genital warts (Veregen® or sinecatechins). Positive efficacy of Polyphenon®E/sinecatechins/Veregen® (PSV) on anogenital warts has been demonstrated in several epidemiological studies and there have been several case reports to show the clinical effectiveness of PSV. In addition, several studies have provided evidence to suggest that PSV is effective in other human papillomavirus (HPV)-related diseases, although some studies failed to show such effects. Since (-)-epigallocatechin gallate (EGCG) is the major component of PSV, the mechanism of the action of PSV might be deduced from that of EGCG. The microarray analysis of the biopsy samples from the patients suggested that apoptosis induction and the downregulation of inflammation are involved in the mechanism of the action of PSV in the clearance of anogenital warts. Cell-based and animal experiments using PSV also demonstrated effects similar to those elicited by EGCG, explaining how PSV works to induce apoptosis and exert anti-inflammatory actions in HPV-related diseases. Future studies would clarify what kinds of diseases respond effectively to PSV, showing health benefits of GTC and EGCG in humans.

| S-EPMC7321293 | biostudies-literature

Green Tea Catechin Dramatically Promotes RNAi Mediated by Low-Molecular-Weight Polymers.

Project description:Cytosolic delivery is the major challenge that limits the clinical translation of siRNA-based therapeutics. Although thousands of polymers have been developed for siRNA delivery, the efficiency-toxicity correlation is unsatisfactory. Here, we report a facile strategy to fabricate core-shell-structured nanoparticles with robust siRNA delivery efficiency. The nanoparticle is prepared by entropy-driven complexation of siRNA with a green tea catechin to yield a negatively charged core, followed by coating low-molecular-weight polymers to form the shell. This supramolecular strategy facilitates the polymers condensing siRNA into uniform nanoparticles. The nanoparticle specifically down-regulates target genes in vitro and in vivo, and efficiently attenuates chronic intestinal inflammation in an inflammatory bowel disease model. Notably, the highly efficient nanoparticles are applicable for various polymers with different topologies and chemical compositions, providing a versatile technique to break down the efficiency-toxicity correlation of cationic polymers. The proposed strategy in this study permits the development of a promising platform for polymer-mediated siRNA delivery.

| S-EPMC6202644 | biostudies-literature

Green tea catechin polyphenols attenuate behavioral and oxidative responses to intermittent hypoxia.

Project description:RationaleThe intermittent hypoxia (IH) that characterizes sleep-disordered breathing impairs spatial learning and increases NADPH oxidase activity and oxidative stress in rodents. We hypothesized that green tea catechin polyphenols (GTPs) may attenuate IH-induced neurobehavioral deficits by reducing IH-induced NADPH oxidase expression, lipid peroxidation, and inflammation.ObjectivesTo assess the effects of GTP administered in drinking water on the cognitive, inflammatory, and oxidative responses to long-term (>14 d) IH during sleep in male Sprague-Dawley rats.MethodsCognitive assessments were conducted in the Morris water maze. We measured levels and expression of malondialdehyde (MDA), prostaglandin E(2), p47(phox) subunit of NADPH oxidase, receptor for advanced glycation end products (RAGE), and glial fibrillary acidic protein expression in rodent brain tissue.Measurements and main resultsGTP treatment prevented IH-induced decreases in spatial bias for the hidden platform during the Morris water maze probe trails as well as IH-induced increases in p47phox expression within the hippocampal CA1 region. In untreated animals, IH exposure was associated with doubling of cortical MDA levels in comparison to room air control animals, and GTP-treated animals exposed to IH showed a 40% reduction in MDA levels. Increases in brain RAGE and glial fibrillary acidic protein expression were observed in IH-exposed animals, and these increases were attenuated in animals treated with GTP.ConclusionsOral GTP attenuates IH-induced spatial learning deficits and mitigates IH-induced oxidative stress through multiple beneficial effects on oxidant pathways. Because oxidative processes underlie neurocognitive deficits associated with IH, the potential therapeutic role of GTP in sleep-disordered breathing deserves further exploration.

| S-EPMC2383994 | biostudies-literature

Effect of Water Hardness on Catechin and Caffeine Content in Green Tea Infusions.

Project description:The health benefits of green tea are associated with its high catechin content. In scientific studies, green tea is often prepared with deionized water. However, casual consumers will simply use their local tap water, which differs in alkalinity and mineral content depending on the region. To assess the effect of water hardness on catechin and caffeine content, green tea infusions were prepared with synthetic freshwater in five different hardness levels, a sodium bicarbonate solution, a mineral salt solution, and deionized water. HPLC analysis was performed with a superficially porous pentafluorophenyl column. As water hardness increased, total catechin yield decreased. This was mostly due to the autoxidation of epigallocatechin (EGC) and epigallocatechin gallate (EGCG). Epicatechin (EC), epicatechin gallate (ECG), and caffeine showed greater chemical stability. Autoxidation was promoted by alkaline conditions and resulted in the browning of the green tea infusions. High levels of alkaline sodium bicarbonate found in hard water can render some tap waters unsuitable for green tea preparation.

| S-EPMC8229914 | biostudies-literature

Bactericidal activity of green tea extracts: the importance of catechin containing nano particles.

Project description:When we drink green tea infusion, we believe we are drinking the extract of the green tea leaves. While practically each tea bag infused in 300 mL water contains about 50 mg of suspended green tea leaf particles. What is the role of these particles in the green tea effect is the objective of this study. These particles (three different size ranges) were isolated via varying speed centrifugation and their respective inputs evaluated. Live oral bacterial samples from human volunteers have been screened against green tea extracts and macro, micro and nano sized green tea particles. The results showed that the presence/absence of the macro and mico sized tea particles in the green tea extract did not contribute much. However, the nano sized particles were characterized to be nature's nano stores of the bioactive catechins. Eradication of these nano tea particles resulted in decrease in the bactericidal property of the green tea extracts. This is a curtain raiser investigation, busting the nano as well as green tea leaf particle contribution in green tea extracts.

| S-EPMC4730195 | biostudies-other

Impact of Green Tea Catechin Ingestion on the Pharmacokinetics of Lisinopril in Healthy Volunteers.

Project description:Lisinopril, a highly hydrophilic long-acting angiotensin-converting enzyme inhibitor, is frequently prescribed for the treatment of hypertension and congestive heart failure. Green tea consumption may reduce the risk of cardiovascular outcomes and total mortality, whereas green tea or its catechin components has been reported to decrease plasma concentrations of a hydrophilic β blocker, nadolol, in humans. The aim of this study was to evaluate possible effects of green tea extract (GTE) on the lisinopril pharmacokinetics. In an open-label, randomized, single-center, 2-phase crossover study, 10 healthy subjects ingested 200 mL of an aqueous solution of GTE containing ~ 300 mg of (-)-epigallocatechin gallate, a major catechin component in green tea, or water (control) when receiving 10 mg of lisinopril after overnight fasting. The geometric mean ratio (GTE/control) for maximum plasma concentration and the area under the plasma concentration-time curve of lisinopril were 0.289 (90% confidence interval (CI) 0.226-0.352) and 0.337 (90% CI 0.269-0.405), respectively. In contrast, there were no significant differences in time to reach maximum lisinopril concentration (6 hours in both phases) and renal clearance of lisinopril (57.7 mL/minute in control vs. 56.9 mL/minute in GTE). These results suggest that the extent of intestinal absorption of lisinopril was significantly impaired in the presence of GTE, whereas it had no major effect on the absorption rate and renal excretion of lisinopril. Concomitant use of lisinopril and green tea may decrease oral exposure to lisinopril, and therefore result in reduced therapeutic efficacy.

| S-EPMC7993260 | biostudies-literature

Green tea extract catechin improves cardiac function in pediatric cardiomyopathy patients with diastolic dysfunction.

Project description:BackgroundOur previous studies have demonstrated that Ca2+ desensitizing catechin could correct diastolic dysfunction in experimental animals with restrictive cardiomyopathy. In this study, it is aimed to assess the effects of green tea extract catechin on cardiac function and other clinical features in pediatric patients with cardiomyopathies.MethodsTwelve pediatric cardiomyopathy patients with diastolic dysfunction were enrolled for the study. Echocardiography, ECG, and laboratory tests were performed before and after the catechin administration for 12 months. Comparison has been made in these patients before and after the treatment with catechin. Next Generation Sequencing was conducted to find out the potential causative gene variants in all patients.ResultsA significant decrease of isovolumetric relaxation time (115 ± 46 vs 100 ± 42 ms, P = 0.047 at 6 months; 115 ± 46 vs 94 ± 30 ms, P = 0.033 at 12 months), an increase of left ventricle end diastolic volume (40 ± 28 vs 53 ± 28 ml, P = 0.028 at 6 months; 40 ± 28 vs 48 ± 33 ml, P = 0.011 at 12 months) and stroke volume (25 ± 16 vs 32 ± 17 ml, P = 0.022 at 6 months; 25 ± 16 vs 30 ± 17 ml, P = 0.021 at 12 months) were observed with echocardiography in these patients 6-month after the treatment with catechin. Ejection fraction, left ventricular wall thickness, biatrial dimension remained unchanged. No significant side effects were observed in the patients tested.ConclusionsThis study indicates that Ca2+ desensitizing green tea extract catechin, is helpful in correcting the impaired relaxation in pediatric cardiomyopathy patients with diastolic dysfunction.

| S-EPMC6505250 | biostudies-literature

Self-assembled metal-phenolic nanocomplexes comprised of green tea catechin for tumor-specific ferroptosis.

Project description:Ferroptosis, a newly discovered form of regulated cell death, has garnered significant attention in the field of tumor therapy. However, the presence of overexpressed glutathione (GSH) and insufficient levels of H2O2 in the tumor microenvironment (TME) hinders the occurrence of ferroptosis. In response to these challenges, here we have constructed the self-assembled nanocomplexes (FeE NPs) utilizing epigallocatechin-3-gallate (EGCG) from green tea polyphenols and metal ions (Fe3+) as components. After grafting PEG, the nanocomplexes (FeE@PEG NPs) exhibit good biocompatibility and synergistically enhanced tumor-inhibitory properties. FeE@PEG NPs can be disassembled by H2O2 in the TME, leading to the rapid release of Fe3+ and EGCG. The released Fe3+ produces large amounts of toxic •OH by the Fenton reactions while having minimal impact on normal cells. The generated •OH effectively induces lipid peroxidation, which leads to ferroptosis in tumor cells. Meanwhile, the released EGCG can autoxidize to produce H2O2, which further promotes the production of •OH radicals and increases lipid peroxide levels. Moreover, EGCG also depletes the high levels of intracellular GSH, leading to an intracellular redox imbalance and triggering ferroptosis. This study provides new insights into advancing anticancer ferroptosis through rational material design, offering promising avenues for future research.

| S-EPMC10999486 | biostudies-literature

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