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1.
BMC Cancer ; 24(1): 486, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632501

ABSTRACT

BACKGROUND: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations. METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment. RESULT: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment. CONCLUSION: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.


Subject(s)
COVID-19 , Catechin , Neoplasms , Pneumonia, Viral , Humans , Catechin/adverse effects , Catechin/analogs & derivatives , Catechin/therapeutic use , Oxygen , Pneumonia, Viral/epidemiology , Prospective Studies , Respiratory Aerosols and Droplets , Treatment Outcome
2.
Acta Pharm ; 74(1): 81-99, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38554388

ABSTRACT

This study aims to assess the chemical composition of the aqueous extract of Cistus albidus L. leaves, as well as the potential of aqueous and hydroethanol extracts of the leaves and seeds as analgesic, anti--inflammatory, and antioxidant agents. The contents of phenolics and inorganic constituents were determined in C. albidus seeds and leaves; antioxidant capacity was assessed by 3 complementary and diverse tests. The carrageenan-induced paw edema technique was used to investigate the anti-inflammatory effect in vivo, and albumin denaturation to evaluate the anti-inflammatory effect in vitro. The acetic acid-induced contortion test, the tail-flick test, and the plantar test were used to assess the analgesic effi cacy in vivo. Chemical analysis was performed by UPLC-MS/MS to quantify several phenolic compounds including catechin (1,627.6 mg kg-1), quercitrin (1,235.8 mg kg-1) and gallic acid (628. 2 mg kg-1). The ICP analysis revealed that potassium and calcium were the main inorganic components in the seeds and leaves of C. albidus. The hydroethanolic extract of the leaves showed the highest content of polyphenols/flavonoids, whereas the highest value of proantho cyanidins was detected in the aqueous extract of the seeds. All extracts showed potent antioxidant activity related to different phenolic compounds (quercetin, gallic acid, astragalin, catechin, and rutin). The aqueous extract of the leaves strongly inhibited paw edema (76.1 %) after 6 h of treatment and showed maximal inhibition of protein denaturation (191.0 µg mL-1 for 50 % inhibition) and analgesic activity in different nociceptive models. The presented data reveal that C. albidus extracts potentially show antioxidant, anti-inflammatory, and analgesic activities that could confirm the traditional use of this plant.


Subject(s)
Catechin , Cistus , Antioxidants/analysis , Cistus/chemistry , Chromatography, Liquid , Catechin/adverse effects , Catechin/analysis , Plant Extracts/chemistry , Pain/chemically induced , Pain/drug therapy , Tandem Mass Spectrometry , Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Phenols/pharmacology , Gallic Acid/adverse effects , Gallic Acid/analysis , Edema/chemically induced , Edema/drug therapy , Plant Leaves/chemistry
3.
Sci Rep ; 13(1): 13865, 2023 08 24.
Article in English | MEDLINE | ID: mdl-37620508

ABSTRACT

To evaluate the safety and effectiveness of epigallocatechin-3-gallate (EGCG) solution treating the acute severe dermatitis in patients receiving radiotherapy. This phase I research enrolled patients with thoracic cancer receiving radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China. EGCG solution was sprayed to the radiation field when grade III radiation-induced dermatitis (RID) first appearance. EGCG concentration escalated from 660 to 2574 µmol/L using modified-Fibonacci dose-escalation. RID and related symptoms were followed up every day. Between March 2021 and November 2021, 19 patients were enrolled in this phase I research. The median dose of grade III RID first observation was 44 Gy (30.6-52 Gy). As the EGCG treatment was performed continuously, all these grade III RID reactions were significantly decreased to grade I or grade II RID at three days after use of EGCG (p < 0.001). Significant relief can be observed in burning sensation (p < 0.001), tractive sensation (p < 0.001), tenderness (p < 0.001), erythema (p < 0.001), itching (p < 0.001) and pain (p < 0.001) after 15 days of EGCG treatment. No radiation therapy delay or interruption for all 19 patients. No adverse events were observed and reported associated with EGCG. The highest dose of this Phase I trial (2574 µmol/L) was recommended for continuous Phase II trial for further evaluation. In this phase I clinical research, use of EGCG solution is safe and can significantly relief grade III RID in patients receiving radiotherapy. Thus, EGCG might be a new choice for acute sever RID.Trial Registration: ClinicalTrials.gov Identifier: NCT02580279 (Full date of first registration: 12/2014).


Subject(s)
Catechin , Dermatitis , Neoplasms , Radiodermatitis , Humans , Neoplasms/complications , Neoplasms/radiotherapy , Catechin/adverse effects , Radiodermatitis/drug therapy , Radiodermatitis/etiology , Acute Disease
4.
Genet Med ; 24(10): 2004-2013, 2022 10.
Article in English | MEDLINE | ID: mdl-35951014

ABSTRACT

PURPOSE: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance. METHODS: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation. RESULTS: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in the EGCG group and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work. CONCLUSION: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population.


Subject(s)
Catechin , Down Syndrome , Catechin/adverse effects , Catechin/analogs & derivatives , Child , Cognition , Dietary Supplements , Double-Blind Method , Down Syndrome/drug therapy , Female , Humans , Male
5.
Nutrients ; 14(15)2022 Jul 30.
Article in English | MEDLINE | ID: mdl-35956325

ABSTRACT

Green-tea-based products and their polyphenols, especially epigallocatechin-3-gallate, have attracted great attention over the years as possible nutraceuticals, due to their promising bioactivities, especially antioxidant and anti-inflammatory, which could be exploited in several diseases, including skin ailments. In this context, the present study aimed at reviewing clinical evidence about the benefits of the oral administration of green tea preparations and its polyphenols to relieve skin disorders, to point out the current knowledge, and to suggest possible novel strategies to effectively exploit the properties of green tea, also managing safety risks. To this end, a systematic review of the existing literature was carried out, using the PRISMA method. Few studies, including five focused on UV-induced erythema and skin alterations, three on photoaging, two on antioxidant skin defenses, and one on acne and genodermatosis, were retrieved. Despite several benefits, clinical evidence only supports the use of oral green tea preparations to protect skin from damage induced by ultraviolet radiation; in other cases, conflicting results and methodological limits of clinical trials do not allow one to clarify their efficacy. Therefore, their application as adjuvant or alternative sunscreen-protective interventions could be encouraged, in compliance with the safety recommendations.


Subject(s)
Camellia sinensis , Catechin , Antioxidants/pharmacology , Catechin/adverse effects , Polyphenols/adverse effects , Skin , Tea , Ultraviolet Rays/adverse effects
6.
Nutrients ; 14(9)2022 Apr 24.
Article in English | MEDLINE | ID: mdl-35565754

ABSTRACT

Dietary supplements for weight management include myriad ingredients with thermogenic, lipotropic, satiety, and other metabolic effects. Recently, the safety of this product category has been questioned. In this review, we summarize the safety evidence as well as relevant clinical findings on weight management and metabolic effects of six representative dietary supplement ingredients: caffeine, green tea extract (GTE), green coffee bean extract (GCBE), choline, glucomannan, and capsaicinoids and capsinoids. Of these, caffeine, GTE (specifically epigallocatechin gallate [EGCG]), and choline have recommended intake limits, which appear not to be exceeded when used according to manufacturers' instructions. Serious adverse events from supplements with these ingredients are rare and typically involve unusually high intakes. As with any dietary component, the potential for gastrointestinal intolerance, as well as possible interactions with concomitant medications/supplements exist, and the health status of the consumer should be considered when consuming these components. Most of the ingredients reviewed also improved markers of metabolic health, such as glucose, lipids, and blood pressure, although the data are limited for some. In summary, weight management supplements containing caffeine, GTE, GCBE, choline, glucomannan, and capsaicinoids and capsinoids are generally safe when taken as directed and demonstrate metabolic health benefits for overweight and obese people.


Subject(s)
Caffeine , Catechin , Antioxidants/analysis , Caffeine/adverse effects , Caffeine/analysis , Catechin/adverse effects , Choline , Dietary Supplements/adverse effects , Humans , Overweight , Plant Extracts/pharmacology , Tea
7.
Neurotoxicology ; 90: 158-171, 2022 05.
Article in English | MEDLINE | ID: mdl-35337893

ABSTRACT

The neurobehavioral, brain redox-stabilizing and neurochemical modulatory properties of catechin and quercetin in rotenone-induced Parkinsonism, and the involvement of NF-κB-mediated inflammation, were investigated. Male Wistar rats subcutaneously administered with multiple doses of 1.5 mg/kg rotenone were post-treated with 5-20 mg/kg catechin or quercetin. This was followed by neurobehavioral evaluation, biochemical estimations, and assessment of neurotransmitter metabolism in the striatum. Expression of genes involved in the canonical pathway for the activation of NF-κB mediated inflammation (IL-1ß, TNF-α, NF-κB, and IκKB) and the pro-apoptotic gene, p53, in the striatum was determined by RT-qPCR. Catechin and quercetin mitigated neurobehavioral deficits caused by rotenone. Both flavonoids attenuated striatal redox stress and neurochemical dysfunction, optimized disturbed dopamine metabolism, and improved depletion of neuron density caused by rotenone toxicity. While administration of catechin produced a more pronounced attenuating effect on IL-1ß, TNF-α, and p53 genes, the attenuating effect of quercetin (20 mg/kg) was more pronounced on NF-κB and IκKB gene expressions when compared to the group administered with rotenone only. Comparatively, quercetin demonstrated superior protection against rotenone neurotoxicity. It is concluded that catechin and quercetin have potential relevance in Parkinson's disease therapy through amelioration of redox stress, optimization of dopamine metabolism, and modulation of anti-inflammatory and anti-apoptotic pathways.


Subject(s)
Catechin , Neuroprotective Agents , Parkinsonian Disorders , Animals , Catechin/adverse effects , Dopamine/metabolism , Genes, p53 , Inflammation/metabolism , Male , NF-kappa B/metabolism , Neuroprotective Agents/therapeutic use , Oxidative Stress , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/drug therapy , Quercetin/pharmacology , Rats , Rats, Wistar , Rotenone/toxicity , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
8.
PLoS One ; 17(2): e0264254, 2022.
Article in English | MEDLINE | ID: mdl-35196359

ABSTRACT

Bone abnormalities affect all individuals with Down syndrome (DS) and are linked to abnormal expression of DYRK1A, a gene found in three copies in people with DS and Ts65Dn DS model mice. Previous work in Ts65Dn male mice demonstrated that both genetic normalization of Dyrk1a and treatment with ~9 mg/kg/day Epigallocatechin-3-gallate (EGCG), the main polyphenol found in green tea and putative DYRK1A inhibitor, improved some skeletal deficits. Because EGCG treatment improved mostly trabecular skeletal deficits, we hypothesized that increasing EGCG treatment dosage and length of administration would positively affect both trabecular and cortical bone in Ts65Dn mice. Treatment of individuals with DS with green tea extract (GTE) containing EGCG also showed some weight loss in individuals with DS, and we hypothesized that weights would be affected in Ts65Dn mice after EGCG treatment. Treatment with ~20 mg/kg/day EGCG for seven weeks showed no improvements in male Ts65Dn trabecular bone and only limited improvements in cortical measures. Comparing skeletal analyses after ~20mg/kg/day EGCG treatment with previously published treatments with ~9, 50, and 200 mg/kg/day EGCG showed that increased dosage and treatment time increased cortical structural deficits leading to weaker appendicular bones in male mice. Weight was not affected by treatment in mice, except for those given a high dose of EGCG by oral gavage. These data indicate that high doses of EGCG, similar to those reported in some treatment studies of DS and other disorders, may impair long bone structure and strength. Skeletal phenotypes should be monitored when high doses of EGCG are administered therapeutically.


Subject(s)
Catechin/analogs & derivatives , Down Syndrome/drug therapy , Muscle, Skeletal/drug effects , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , Animals , Catechin/administration & dosage , Catechin/adverse effects , Catechin/therapeutic use , Down Syndrome/metabolism , Drug Administration Schedule , Female , Male , Mice , Muscle, Skeletal/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Dyrk Kinases
9.
Immunopharmacol Immunotoxicol ; 44(1): 58-66, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34845949

ABSTRACT

AIM: Acute lung injury (ALI) and resultant acute respiratory distress syndrome (ARDS) are detrimental inflammatory disease associated with high rates of morbidity and mortality due to a lack of effective treatment options. Previous study has demonstrated that an inhibition of geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1) show a protective effect against ALI. METHOD: In this study, by using connective map (CMAP), we identified catechin as a potential drug to exhibit similar effects to inhibit GGPPS1. Furthermore, we detected the protective effect of catechin on lipopolysaccharide (LPS)-induced ALI and delineated the underlying mechanism. RESULTS: We found that catechin effectively ameliorated LPS-induced lung inflammation and alleviated the release of cytokines into alveolar space. Notably, miR-182/GGPPS1 signaling pathway was reactivated upon catechin administration, which was essential for the catechin-induced protective effect against ALI. CONCLUSION: catechin regulates miR-182/GGPPS1 signaling pathway and efficaciously ameliorates LPS-induced acute lung injury in mice model, which provided a promising therapeutic strategy in ALI and ARDS.


Subject(s)
Acute Lung Injury , Catechin , MicroRNAs , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Animals , Catechin/adverse effects , Catechin/metabolism , Lipopolysaccharides/toxicity , Lung/metabolism , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Signal Transduction
11.
Cancer Prev Res (Phila) ; 14(5): 573-580, 2021 05.
Article in English | MEDLINE | ID: mdl-33648940

ABSTRACT

Polyphenon E (Poly E) is a green tea polyphenol preparation whose most active component is epigallocatechin gallate (EGCG). We studied the cancer preventive efficacy and safety of Poly E in subjects with rectal aberrant crypt foci (ACF), which represent putative precursors of colorectal cancers. Eligible subjects had prior colorectal advanced adenomas or cancers, and had ≥5 rectal ACF at a preregistration chromoendoscopy. Subjects (N = 39) were randomized to 6 months of oral Poly E (780 mg EGCG) daily or placebo. Baseline characteristics were similar by treatment arm (all P >0.41); 32 of 39 (82%) subjects completed 6 months of treatment. The primary endpoint was percent reduction in rectal ACF at chromoendoscopy comparing before and after treatment. Among 32 subjects (15 Poly E, 17 placebo), percent change in rectal ACF number (baseline vs. 6 months) did not differ significantly between study arms (3.7% difference of means; P = 0.28); total ACF burden was also similar (-2.3% difference of means; P = 0.83). Adenoma recurrence rates at 6 months were similar by arm (P > 0.35). Total drug received did not differ significantly by study arm; 31 (79%) subjects received ≥70% of prescribed Poly E. Poly E was well tolerated and adverse events (AE) did not differ significantly by arm. One subject on placebo had two grade 3 AEs; one subject had grade 2 hepatic transaminase elevations attributed to treatment. In conclusion, Poly E for 6 months did not significantly reduce rectal ACF number relative to placebo. Poly E was well tolerated and without significant toxicity at the dose studied. PREVENTION RELEVANCE: We report a chemoprevention trial of polyphenon E in subjects at high risk of colorectal cancer. The results show that polyphenon E was well tolerated, but did not significantly reduce the number of rectal aberrant crypt foci, a surrogate endpoint biomarker of colorectal cancer.


Subject(s)
Aberrant Crypt Foci/drug therapy , Catechin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Neoplasm Recurrence, Local/prevention & control , Aberrant Crypt Foci/diagnosis , Aberrant Crypt Foci/pathology , Aged , Catechin/administration & dosage , Catechin/adverse effects , Colon/diagnostic imaging , Colon/drug effects , Colon/pathology , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Intestinal Mucosa/diagnostic imaging , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/pathology , Placebos/administration & dosage , Placebos/adverse effects , Rectum/diagnostic imaging , Rectum/drug effects , Rectum/pathology , Treatment Outcome
12.
BJOG ; 128(6): 1047-1055, 2021 05.
Article in English | MEDLINE | ID: mdl-33075197

ABSTRACT

OBJECTIVE: To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). DESIGN: A Phase II double-blind randomised control trial. SETTING: A tertiary gynaecological oncology referral centre. POPULATION: All women diagnosed with primary and recurrent uVIN. METHODS: Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. MAIN OUTCOME MEASURES: The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. RESULTS: There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. CONCLUSION: Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. TWEETABLE ABSTRACT: A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.


Subject(s)
Camellia sinensis , Carcinoma in Situ , Catechin/analogs & derivatives , Vulvar Neoplasms , Adult , Antineoplastic Agents/pharmacology , Carcinoma in Situ/drug therapy , Carcinoma in Situ/pathology , Catechin/administration & dosage , Catechin/adverse effects , Double-Blind Method , Female , Humans , Ointments/administration & dosage , Ointments/adverse effects , Plant Extracts/pharmacology , Treatment Outcome , Vulvar Neoplasms/drug therapy , Vulvar Neoplasms/pathology
13.
Oxid Med Cell Longev ; 2020: 9723686, 2020.
Article in English | MEDLINE | ID: mdl-32850004

ABSTRACT

Epigallocatechin-3-gallate (EGCG) is the major polyphenolic compound present in green tea and is generally regarded as an effective antioxidant. However, its chemical reactivity makes it susceptible to generate reactive oxygen species (ROS) via autooxidation and exhibit prooxidant effects. The prooxidant actions of EGCG could play a dual role, being both beneficial and harmful. This review summarized recent research progress on (1) the anticancer, antiobesity, and antibacterial effects of EGCG and (2) the possible toxicity of EGCG. The major focus is on the involvement of prooxidant effects of EGCG and their effective doses used. Considering dosage is a crucial factor in the prooxidant effects of EGCG; further studies are required to find the appropriate dose at which EGCG could bring more health benefits with lower toxicity.


Subject(s)
Catechin/analogs & derivatives , Health , Reactive Oxygen Species/toxicity , Animals , Catechin/adverse effects , Catechin/chemistry , Humans , Lipid Metabolism/drug effects , Models, Biological , Oxidation-Reduction
14.
Int J Mol Sci ; 21(4)2020 Feb 19.
Article in English | MEDLINE | ID: mdl-32092951

ABSTRACT

Epigallocatechin gallate (EGCG) is an inhibitor of DYRK1A, a serine/threonine kinase considered to be a major contributor of cognitive dysfunctions in Down syndrome (DS). Two clinical trials in adult patients with DS have shown the safety and efficacy to improve cognitive phenotypes using commercial green tea extract containing EGCG (45% content). In the present study, we performed a preclinical study using FontUp®, a new nutritional supplement with a chocolate taste specifically formulated for the nutritional needs of patients with DS and enriched with a standardized amount of EGCG in young mice overexpressing Dyrk1A (TgBACDyrk1A). This preparation is differential with previous one used, because its green tea extract has been purified to up 94% EGCG of total catechins. We analyzed the in vitro effect of green tea catechins not only for EGCG, but for others residually contained in FontUp®, on DYRK1A kinase activity. Like EGCG, epicatechin gallate was a noncompetitive inhibitor against ATP, molecular docking computations confirming these results. Oral FontUp® normalized brain and plasma biomarkers deregulated in TgBACDyrk1A, without negative effect on liver and cardiac functions. We compared the bioavailability of EGCG in plasma and brain of mice and have demonstrated that EGCG had well crossed the blood-brain barrier.


Subject(s)
Brain/drug effects , Catechin/analogs & derivatives , Down Syndrome/diet therapy , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , Tea/chemistry , Animals , Antioxidants/administration & dosage , Antioxidants/therapeutic use , Biological Availability , Biomarkers/blood , Biomarkers/metabolism , Blood-Brain Barrier/drug effects , Brain/metabolism , Brain/pathology , Brain/ultrastructure , Catechin/administration & dosage , Catechin/adverse effects , Catechin/chemistry , Catechin/therapeutic use , Dietary Supplements , Down Syndrome/blood , Down Syndrome/enzymology , Down Syndrome/metabolism , Liver/drug effects , Liver/metabolism , Mice , Mice, Inbred C57BL , Microscopy, Electron, Scanning , Molecular Docking Simulation , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/therapeutic use , Polyphenols/analysis , Protein Serine-Threonine Kinases/chemistry , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Protein-Tyrosine Kinases/chemistry , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Up-Regulation , Dyrk Kinases
15.
J Cardiovasc Pharmacol ; 75(4): 292-298, 2020 04.
Article in English | MEDLINE | ID: mdl-31895874

ABSTRACT

Healthy vascular endothelial cells regulate vascular tone and permeability, prevent vessel wall inflammation, enhance thromboresistance, and contribute to general vascular health. Furthermore, they perform important functions including the production of vasoactive substances such as nitric oxide (NO) and endothelium-derived hyperpolarizing factors, as well as the regulation of smooth muscle cell functions. Conversely, vascular endothelial dysfunction leads to atherosclerosis, thereby enhancing the risk of stroke, myocardial infarction, and other cardiovascular diseases (CVDs). Observational studies and randomized trials showed that green tea intake was inversely related to CVD risk. Furthermore, evidence indicates that epigallocatechin gallate (EGCG) found in green tea might exert a preventive effect against CVDs. EGCG acts as an antioxidant, inducing NO release and reducing endothelin-1 production in endothelial cells. EGCG enhances the bioavailability of normal NO by reducing levels of the endogenous NO inhibitor asymmetric dimethylarginine. Furthermore, it inhibits the enhanced expression of adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and attenuates monocyte adhesion. In addition, EGCG prevents enhanced oxidative stress through the Nrf2/HO-1 pathway. These effects indicate that it might prevent the production of reactive oxygen species, inhibit inflammation, and reduce endothelial cell apoptosis during the initial stages of atherosclerosis. The current review summarizes recent research in this area and discusses novel findings regarding the protective effect of EGCG on endothelial dysfunction and CVDs in general.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Atherosclerosis/drug therapy , Catechin/analogs & derivatives , Endothelial Cells/drug effects , Endothelium, Vascular/drug effects , Animals , Anti-Inflammatory Agents/adverse effects , Antioxidants/adverse effects , Apoptosis/drug effects , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atherosclerosis/physiopathology , Catechin/adverse effects , Catechin/therapeutic use , Cell Adhesion Molecules/metabolism , Endothelial Cells/metabolism , Endothelial Cells/pathology , Endothelin-1/metabolism , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Endothelium, Vascular/physiopathology , Humans , Nitric Oxide/metabolism , Oxidative Stress/drug effects
16.
Nutrients ; 12(2)2020 Jan 23.
Article in English | MEDLINE | ID: mdl-31979305

ABSTRACT

BACKGROUND: Due to the inflammatory nature of multiple sclerosis (MS), interleukin 6 (IL-6) is high in blood levels, and it also increases the levels of anxiety related to functional disability. Epigallocatechin gallate (EGCG) decreases IL-6, which could be enhanced by the anti-inflammatory effect of high ketone bodies after administering coconut oil (both of which are an anxiolytic). Therefore, the aim of this study was to assess the impact of coconut oil and EGCG on the levels of IL-6, anxiety and functional disability in patients with MS. METHODS: A pilot study was conducted for four months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Both groups followed the same isocaloric Mediterranean diet. State and trait anxiety were determined before and after the study by means of the State-Trait Anxiety Inventory (STAI). In addition, IL-6 in serum was measured using the ELISA technique and functional capacity was determined with the Expanded Disability Status Scale (EDSS) and the body mass index (BMI). RESULTS: State anxiety and functional capacity decreased in the intervention group and IL-6 decreased in both groups. CONCLUSIONS: EGCG and coconut oil improve state anxiety and functional capacity. In addition, a decrease in IL-6 is observed in patients with MS, possibly due to the antioxidant capacity of the Mediterranean diet and its impact on improving BMI.


Subject(s)
Anxiety/diet therapy , Catechin/analogs & derivatives , Coconut Oil/administration & dosage , Diet, Mediterranean , Dietary Supplements , Interleukin-6/blood , Multiple Sclerosis, Chronic Progressive/diet therapy , Multiple Sclerosis, Relapsing-Remitting/diet therapy , Anxiety/blood , Anxiety/diagnosis , Anxiety/psychology , Biomarkers/blood , Body Mass Index , Catechin/administration & dosage , Catechin/adverse effects , Coconut Oil/adverse effects , Diet, Mediterranean/adverse effects , Dietary Supplements/adverse effects , Disability Evaluation , Emotions , Female , Humans , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/blood , Multiple Sclerosis, Chronic Progressive/diagnosis , Multiple Sclerosis, Chronic Progressive/psychology , Multiple Sclerosis, Relapsing-Remitting/blood , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Multiple Sclerosis, Relapsing-Remitting/psychology , Pilot Projects , Prospective Studies , Recovery of Function , Spain , Time Factors , Treatment Outcome
17.
Invest New Drugs ; 38(4): 1129-1136, 2020 08.
Article in English | MEDLINE | ID: mdl-31701429

ABSTRACT

Radiation-induced oral mucositis has a dismal outcome with limited treatment options. We conducted a phase I study to evaluate the safety and preliminary efficacy of epigallocatechin-3-gallate (EGCG) mouthwash when given along with radiation in head and neck cancer. Patients with pathologically confirmed head and neck cancer were eligible for this study. EGCG mouthwash was administered at the assigned dosage level (starting at 440 µmol/L, three times a day) in a standard 3 + 3 dose escalation design. Mucosal toxicity, patient satisfaction, and mucositis-related pain (MTP) were assessed weekly. The primary endpoint was safety of EGCG, and the secondary endpoint was to determine the relief of the mucositis symptom. The pre- and post-treatment parameters were compared using the paired t-test. 20 patients were enrolled. The maximum tolerated dose of the EGCG mouthwash was 2200 µmol/L. Burning (n = 1/20) and nausea (n = 3/20) were the most common toxicities. No patients experienced WHO Grade 3 or higher mucositis. MTP scores significantly decreased after EGCG administration over time (p < 0.05). Adding EGCG mouthwash to radiotherapy is feasible without increasing toxicities. The recommended dose for phase II study is determined to be 1760 µmol/L, and EGCG administration reduces radiation-induced oral mucosal injury in patients.


Subject(s)
Catechin/analogs & derivatives , Chemoradiotherapy , Head and Neck Neoplasms/therapy , Mouthwashes/administration & dosage , Mucositis/drug therapy , Radiation Injuries/drug therapy , Adult , Aged , Catechin/administration & dosage , Catechin/adverse effects , Humans , Maximum Tolerated Dose , Middle Aged , Mouth Mucosa/drug effects , Mouthwashes/adverse effects , Mucositis/etiology , Prospective Studies , Young Adult
18.
Sci Rep ; 9(1): 13593, 2019 09 19.
Article in English | MEDLINE | ID: mdl-31537880

ABSTRACT

Emergence of new molecules acting directly on the hepatitic C virus (HCV) has improved treatment outcomes. However, there is a risk of selecting viral escape mutants, so a new combination is needed using different inhibitors that target different steps of the HCV infectious cycle. Novel single tablet formulations were developed: Dactavira, composed of sofosbuvir (SOF) 400 mg/daclatisvir (DCV) 60 mg/epigallocatechin gallate (EGCG) 400 mg without ribavirin (RBV); and Dactavira plus, which includes RBV 800 mg. A randomized, open-label study was carried out on treatment-naïve non-cirrhotic (Group A, n = 50) and treatment-naïve cirrhotic (Group B, n = 22) patients with genotype 4 HCV infection. Group A was randomly assigned to receive a single daily fixed-dose (Dactavira, n = 25) or the standard of care [SOF 400 mg/DCV 60 mg] (n = 25) daily for 12 weeks. Group B was randomly assigned to receive a single daily fixed-dose (Dactavira plus, n = 11) or the standard of care + RBV 800 mg (n = 11) daily for 12 weeks. Patients receiving Dactavira or Dactavira plus had a significantly more rapid rate of viral load decline as compared to patients receiving the standard of care therapy. Sustained virological response for 12 weeks for Dactavira or Dactavira plus showed no statistically significant difference when compared to the standard of care. Also, they did not affect normal hemoglobin levels (p < 0.001) versus the standard of care. The incorporated EGCG interferes with the viral entry mechanisms, as reported by several investigators, and in turn enhances efficacy and prevents relapse as compared to the standard of care. Also, its antihemeolytic and antifibrotic activities may improve the safety and tolerability of the therapy.


Subject(s)
Catechin/analogs & derivatives , Daclizumab/administration & dosage , Hepatitis C, Chronic/drug therapy , Ribavirin/administration & dosage , Sofosbuvir/administration & dosage , Adult , Catechin/administration & dosage , Catechin/adverse effects , Daclizumab/adverse effects , Drug Administration Schedule , Drug Therapy, Combination/adverse effects , Female , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , Pilot Projects , Random Allocation , Ribavirin/adverse effects , Sofosbuvir/adverse effects , Standard of Care , Sustained Virologic Response , Tablets , Treatment Outcome , Viral Load/drug effects
19.
Med Hypotheses ; 133: 109402, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31557595

ABSTRACT

The dried root of the angiosperm Scutellaria baicalensis, also known as Chinese skullcap or Baikal skullcap, is widely used in traditional Chinese medicine, Korean traditional medicine and as a nutritional supplement; several studies have indicated that both the supplement and some of its ingredients may have clinically beneficial actions. However, the National Institutes of Health official guidance states that the use of Scutellaria "has been implicated in rare instances of clinically apparent liver injury" and that "the onset of symptoms and jaundice occurred within 6-24 weeks of starting skullcap, and the serum enzyme pattern was typically hepatocellular", with marked increases in serum alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin levels. Careful perusal of all such published case reports showed that in each case the patient was concurrently taking at least one other supplement which had an established association with hepatic dysfunction. The authors hypothesised that long-term supplementation with Scutellaria baicalensis does not lead to hepatic dysfunction. The aim of this study was to test this hypothesis by assessing liver function before and after starting supplementation with Scutellaria baicalensis. Pre- and post-supplementation serum assays of alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin were carried out in 17 patients (16 female) of average age 38.6 (standard error 4.4) years who had each taken 1335 mg dried root daily for an average of 444 (71) days. The mean baseline versus follow-up values for each liver function test were: alanine transaminase: 25.7 (2.6) IU/L v. 25.1 (1.7) IU/L; aspartate transaminase: 22.1 (1.1) IU/L v. 23.5 (1.3) IU/L; alkaline phosphatase: 63.7 (4.6) IU/L v. 63.3 (3.9) IU/L; and bilirubin: 6.1 (0.6) µM v. 6.0 (0.7) µM. None of these changes was statistically significant; indeed, three of the four parameters showed a non-significant decrease over time. Furthermore, none manifested clinical symptoms or signs of hepatic dysfunction during Scutellaria supplementation. These results suggest that daily intake of a relatively high level of Scutellaria baicalensis for over a year is not associated with any biochemical or clinical evidence of hepatic dysfunction. Indeed, Scutellaria baicalensis has been shown in murine experiments to have hepatoprotective actions.


Subject(s)
Chemical and Drug Induced Liver Injury/etiology , Dietary Supplements/adverse effects , Scutellaria baicalensis/adverse effects , Adult , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Aspartate Aminotransferases/blood , Bilirubin/blood , Biomarkers/blood , Catechin/adverse effects , Chemical and Drug Induced Liver Injury/blood , Drug Combinations , Drugs, Chinese Herbal/adverse effects , Female , Follow-Up Studies , Herb-Drug Interactions , Humans , Male , Phytotherapy/adverse effects , Plant Roots/adverse effects , Plant Roots/chemistry , Tea/adverse effects
20.
Lancet Neurol ; 18(8): 724-735, 2019 08.
Article in English | MEDLINE | ID: mdl-31278067

ABSTRACT

BACKGROUND: Multiple system atrophy is a rare neurodegenerative disease characterised by aggregation of α-synuclein in oligodendrocytes and neurons. The polyphenol epigallocatechin gallate inhibits α-synuclein aggregation and reduces associated toxicity. We aimed to establish if epigallocatechin gallate could safely slow disease progression in patients with multiple system atrophy. METHODS: We did a randomised, double-blind, parallel group, placebo-controlled clinical trial at 12 specialist centres in Germany. Eligible participants were older than 30 years; met consensus criteria for possible or probable multiple system atrophy and could ambulate independently (ie, were at Hoehn and Yahr stages 1-3); and were on stable anti-Parkinson's, anti-dysautonomia, anti-dementia, and anti-depressant regimens (if necessary) for at least 1 month. Participants were randomly assigned (1:1) to epigallocatechin gallate or placebo (mannitol) via a web-generated permuted blockwise randomisation list (block size=2) that was stratified by disease subtype (parkinsonism-predominant disease vs cerebellar-ataxia-predominant disease). All participants and study personnel were masked to treatment assignment. Participants were given one hard gelatin capsule (containing either 400 mg epigallocatechin gallate or mannitol) orally once daily for 4 weeks, then one capsule twice daily for 4 weeks, and then one capsule three times daily for 40 weeks. After 48 weeks, all patients underwent a 4-week wash-out period. The primary endpoint was change in motor examination score of the Unified Multiple System Atrophy Rating Scale (UMSARS) from baseline to 52 weeks. Efficacy analyses were done in all people who received at least one dose of study medication. Safety was analysed in all people who received at least one dose of the study medication to which they had been randomly assigned. This trial is registered with ClinicalTrials.gov (NCT02008721) and EudraCT (2012-000928-18), and is completed. FINDINGS: Between April 23, 2014, and Sept 3, 2015, 127 participants were screened and 92 were randomly assigned-47 to epigallocatechin gallate and 45 to placebo. Of these, 67 completed treatment and 64 completed the study (altough one of these patients had a major protocol violation). There was no evidence of a difference in the mean change from baseline to week 52 in motor examination scores on UMSARS between the epigallocatechin gallate (5·66 [SE 1·01]) and placebo (6·60 [0·99]) groups (mean difference -0·94 [SE 1·41; 95% CI -3·71 to 1·83]; p=0·51). Four patients in the epigallocatechin gallate group and two in the placebo group died. Two patients in the epigallocatechin gallate group had to stop treatment because of hepatotoxicity. INTERPRETATION: 48 weeks of epigallocatechin gallate treatment did not modify disease progression in patients with multiple system atrophy. Epigallocatechin gallate was overall well tolerated but was associated with hepatotoxic effects in some patients, and thus doses of more than 1200 mg should not be used. FUNDING: ParkinsonFonds Deutschland, German Parkinson Society, German Neurology Foundation, Lüneburg Foundation, Bischof Dr Karl Golser Foundation, and Dr Arthur Arnstein Foundation.


Subject(s)
Catechin/analogs & derivatives , Multiple System Atrophy/drug therapy , Neuroprotective Agents/therapeutic use , Aged , Catechin/adverse effects , Catechin/therapeutic use , Disease Progression , Double-Blind Method , Female , Germany , Humans , Male , Middle Aged , Treatment Outcome
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