Previfenon (epigallocatechin gallate) / MELISA Institute - LARVOL DELTA

[PREPRINT] The synergistic anti-Warburg efficacy of temozolomide, metformin and epigallocatechin gallate in glioblastoma (bioRxiv) - "Methodology: Based on this lacuna, the current study aimed to explore the therapeutic efficacy of the triple-drug combination of temozolomide, metformin and epigallocatechin gallate in attenuating Warburg effect and glucose uptake in glioblastoma both in vitro and in vivo. Results: Our results showed that the triple-drug combination had significantly reduced glucose uptake and reversed the Warburg effect in glioblastoma cells and in the xenograft-induced glioma rat model. Conclusion: Thus, the triple-drug combination would serve as an effective therapeutic regime to hamper glioblastoma progression via altering glucose metabolism and improve the overall prognosis in patient setting."

Preclinical • Preprint • Glioblastoma • Glioma • Oncology

[PREPRINT] A combination of Metformin and Epigallocatechin Gallate Potentiates Glioma Chemotherapy in vivo (bioRxiv) - “In this study, we investigated the therapeutic benefits of combining three repurposed drugs, namely, metformin (anti-diabetic) and epigallocatechin gallate (green tea-derived antioxidant) together with temozolomide in a glioma-induced xenograft rat model. Our triple-drug combination therapy significantly inhibited tumor growth in vivo and increased the survival rate (50%) of rats when compared with individual or dual treatments. Molecular and cellular analyses revealed that our triple-drug cocktail treatment inhibited glioma tumor growth in rat model through ROS-mediated inactivation of PI3K/AKT/mTOR pathway, arrest of the cell cycle at G1 phase and induction of molecular mechanisms of caspases-dependent apoptosis.”

Preclinical • Preprint • Glioma • Oncology

[VIRTUAL] A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of Epigallocatechin-Gallate in the Prevention of Radiation-Induced Dermatitis (ASTRO 2020) - P2 | "Prophylactic use of EGCG solution substantially reduced the incidence and severity of RID in patients receiving adjuvant radiotherapy and could be a new standard of skin care for patients receiving adjuvant radiotherapy."

Clinical • P2 data • Breast Cancer • Dermatitis • Dermatology • Hematological Disorders • Immunology • Leukopenia • Oncology • Pain • Pruritus • Solid Tumor

Application of a Reactive Oxygen Species-Responsive Drug-Eluting Coating for Surface Modification of Vascular Stents. (PubMed, ACS Appl Mater Interfaces) - "Two functional molecules, epigallocatechin gallate (EGCG) and cysteine hydrochloride, were employed to fabricate a coating on the surface of 316L stainless steel. In addition, the coating was used as a drug carrier to load pitavastatin calcium...A positive correlation was observed between the rate of drug release and the degree of oxidative stress. Collectively, this drug-loaded oxidative stress-responsive coating has been demonstrated to significantly inhibit inflammation, accelerate endothelialization, and reduce the risk of restenosis of vascular stents in vivo."

Journal • Cardiovascular • Coronary Artery Disease • Heart Failure • Hematological Disorders • Immunology • Inflammation • Thrombosis

Quenching effects of (-)-Epigallocatechin gallate for singlet oxygen production and its protection against oxidative damage induced by Ce6-mediated photodynamic therapy in vitro. (PubMed, Photodiagnosis Photodyn Ther) - "EGCG is an efficient quencher for both triplet-state photosensitizers and O. The quenching ability of EGCG during photosensitization for selected photosensitizers is: RB > HiPorfin > Ce6 > AlPcS. EGCG could be used to protect normal cells and tissue against oxidative damage."

Journal • Preclinical

[VIRTUAL] PENSA study for the prevention of cognitive decline in APOE-ɛ4 carriers with subjective cognitive decline: Baseline preliminary demographic and neuropsychological description of the study population. (AAIC 2021) - "The aim of the study is to evaluate the efficacy of a multimodal personalized lifestyle intervention (dietary and physical activity counseling and cognitive training) combined with a dietary supplement, epigallocatechin gallate (EGCG) in slowing down cognitive decline... The PENSA study will provide valuable information on the effect of a lifestyle intervention supplemented with EGCG to prevent cognitive decline and will aid to share light on the benefit of these strategies in people at-risk of developing AD."

Clinical • Alzheimer's Disease • CNS Disorders • Depression • Mood Disorders • Psychiatry • APOE

[VIRTUAL] Combination of baicalein and trans -chalcone synergistically reduces amyloid beta and its toxicity in yeast. (AAIC 2021) - " Eleven selected naturally occurring bioactive compounds namely mangiferin, quercetin, rutin, resveratrol, epigallocatechin gallate (EGCG), urolithin A, oleuropein, rosmarinic acid, salvianolic acid B, baicalein and trans -chalcone at specific concentration (50µM) were screened for their ability to change intracellular green fluorescent protein (GFP) tagged Aβ42 levels, in vivo anti-amyloid properties using thioflavin-S fluorescent dye and induce heat stress response using the yeast heat stress reporter that expresses mCherry red fluorescent protein under control of a heat shock promoter containing heat shock elements (HSEs)... The findings of the study suggest that the combination of baicalein and trans -chalcone can be a therapeutic strategy to cure or at least prevent AD. However, further studies are recommended to ascertain that similar cytoprotective activity is observed in humans and optimization of dosage to observe best effect."

Palliative care

Epigallocatechin Gallate Alleviates Down-Regulation of Thioredoxin in Ischemic Brain Damage and Glutamate-Exposed Neuron. (PubMed, Neurochem Res) - "However, this effect of EGCG on caspase-3 change was weakened in thioredoxin siRNA-transfected neurons. These findings suggest that EGCG exerts a neuroprotective effect by regulating thioredoxin expression and modulating ASK1 and thioredoxin binding in ischemic brain damage."

Journal • CNS Disorders • Vascular Neurology • CASP3 • TXN

Phytochemicals as regulators of Th17/Treg balance in inflammatory bowel diseases. (PubMed, Biomed Pharmacother) - "Recently, a growing body of studies has indicated that phytochemicals derived from natural products are potent regulators of Th17/Treg, and exert preferable protective benefits against colonic inflammation. In this review, the great potential of anti-colitis agents derived from natural products through targeting Th17/Treg cells and their action mechanisms for the treatment or prevention of IBD in recent research is summarized, which may help further the development of new drugs for IBD treatment."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Stability and antioxidant capacity of epigallocatechin gallate in Dulbecco's modified eagle medium. (PubMed, Food Chem) - "The antioxidative activity of EGCG in DMEM was determined by DPPH, ABTS and FRAP assay. The antioxidative properties of EGCG continuously decreased over 8 h in DMEM, which was consistent with its course of degradation."

Journal

Antimelanogenesis Effects of Theasinensin A. (PubMed, Int J Mol Sci) - "This compound is also manufactured with epigallocatechin gallate (EGCG) as a substrate and is refined after the enzyme reaction...We also confirmed α-MSH-mediated CREB activities through a luciferase reporter assay, and that the quantities of cAMP were reduced by TSA in the enzyme linked immunosorbent assay (ELISA) results. Based on these findings, TSA should be considered an effective inhibitor of hyperpigmentation."

Journal • Immunology • Inflammation • Melanoma • Oncology • Ophthalmology • Solid Tumor • DCT • MITF • PCR • Tyrosinase • TYRP1

Oral epigallocatechin gallate reduces intestinal nadolol absorption via modulation of Oatp1a5 and Oct1 transcriptional levels in spontaneously hypertensive rats. (PubMed, Phytomedicine) - "These data concluded that exposure to EGCG could lead to reduced nadolol bioavailability and therefore, uncontrolled raised blood pressure and higher risks of cardiovascular events. Our data suggest that the reduced nadolol bioavailability is associated with the downregulation of ileal Oatp1a5 and Oct1 mRNA levels that subsequently lead to poor absorption of nadolol to the systemic circulation."

Journal • Preclinical • Cardiovascular • Hypertension • SLC22A1

Prediction of combination therapies based on topological modeling of the immune signaling network in multiple sclerosis. (PubMed, Genome Med) - "Our approach based on donor-specific signaling networks enables prediction of targets for combination therapy for MS and other complex diseases."

Combination therapy • Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • IFNB1 • TGFB1

The Phytochemical Profile and Biological Activity of Liquidambar orientalis Mill. var. orientalis via NF-κB and Apoptotic Pathways in Human Colorectal Cancer. (PubMed, Nutr Cancer) - "Regarding chemical composition, quercetin 3-glucoside (61.005 ± 1.527 mg/g extract), chlorogenic acid (31.627 ± 0.970 mg/g extract), pyrogallol (9.950 ± 0.001 mg/g extract), epigallocatechin gallate (9.671 ± 0.004 mg/g extract), apigenin 7-O-glucoside (2.687 ± 0.027 mg/g extract), gallic acid (2.137 ± 0.012 mg/g extract), genistin (1.270 ± 0.027 mg/g extract), luteolin (0.055 ± 0.0005 mg/g extract) and kaempferol (0.506 ± 0.007 mg/g extract) were identified as the major phytochemical compounds. Our results showed that LM extract exhibited In Vitro cytotoxic and apoptotic properties."

Journal • Colorectal Cancer • Dermatology • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Peptic Ulcer • Solid Tumor

A comparative study of anti-leukemic effects of kaempferol and epigallocatechin-3-gallate (EGCG) on human leukemia HL-60 cells. (PubMed, Avicenna J Phytomed) - "The present study compared the molecular mechanism induced by kaempferol and epigallocatechin gallate (EGCG) as well as all-trans retinoic acid (ATRA), in HL-60 leukemia cells during five days...In addition, kaempferol and EGCG increased apoptosis and inhibited MDR in a concentration- and time-dependent manner. Kaempferol at high concentrations can be taken into consideration for treating patients with APL as compared with EGCG."

Journal • Acute Promyelocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ABCB1 • ABCC1 • BCL2 • CASP3 • CASP8 • CASP9 • CDKN1A • PTEN

Tissue engineered artificial liver model based on viscoelastic hyaluronan-collagen hydrogel and the effect of EGCG intervention on ALD. (PubMed, Colloids Surf B Biointerfaces) - "Furthermore, epigallocatechin gallate (EGCG) as an intervention on ALD was confirmed in both in vitro and in vivo model. The findings indicate our simple artificial liver model is not only highly predictive but also easy to apply to drug screening and implantation studies, suggesting a promising alternative to animal models. Moreover, as the main active ingredient of tea, EGCG's effective intervention and reversal effect on fatty liver provides support for the theory that green tea could prevent alcoholic fatty liver."

Journal • Hepatology

Sodium/taurocholate cotransporting polypeptide as target therapy for liver fibrosis. (PubMed, Gut) - "NTCP expression is linearly correlated with fibrosis severity. Modulated BA trafficking could be an important step in LF pathogenesis. Antagonising BA uptake may suggest a therapeutic strategy for preventing disease progression."

Journal • Fibrosis • Hepatology • Immunology • Leptin Receptor Deficiency Obesity • Liver Cirrhosis • LEP

Structural and mechanistic insights into amyloid-β and α-synuclein fibril formation and polyphenol inhibitor efficacy in phospholipid bilayers. (PubMed, FEBS J) - "Large unilamellar vesicles (LUVs) were shown to increase fibrillization and largely decrease the effectiveness of two well-known polyphenol fibril inhibitors, (-)-epigallocatechin gallate (EGCG) and resveratrol, however, use of immunoblotting and ion-mobility mass spectrometry revealed this occurs through varying mechanisms...Competing effects of the lipids and inhibitor, along with reduced inhibitor binding in the presence of LUVs, provides a mechanistic understanding for decreased inhibitor efficacy in a lipid environment. Together, this study highlights that amyloid inhibitor design may be misguided if effects of lipid membrane composition and architecture are not considered during development."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Fabrication of Zein-Lecithin-EGCG complex nanoparticles: Characterization, controlled release in simulated gastrointestinal digestion. (PubMed, Food Chem) - "The Zein-Lecithin-Epigallocatechin gallate (EGCG) complex nanoparticles were fabricated by anti-solvent coprecipitation method...Fluorescence spectroscopy (FL), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) experiments revealed that the EGCG was successfully encapsulated by Z-L nanocomplexes through electrostatic, hydrophobic and hydrogen bonding interactions. The Zein-Lecithin-EGCG complex nanoparticles exhibited excellent stability and great sustained-release performance, which will be the alternative for potential application in the food industry."

Journal • Gastrointestinal Disorder

Pharmacokinetics and Hepatic Safety of EGCG (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Yale University; Trial primary completion date: Jun 2021 ➔ Sep 2021

Clinical • Trial primary completion date • Gynecology • Solid Tumor • Uterine Leiomyoma

Glutathione- and apolipoprotein E-grafted liposomes to regulate mitogen-activated protein kinases and rescue neurons in Alzheimer's disease. (PubMed, Mater Sci Eng C Mater Biol Appl) - "Phosphatidylcholine (PC)-liposomes carrying curcumin (CURC), quercetin (QU), epigallocatechin gallate (EGCG) and rosmarinic acid (RA) with crosslinked glutathione (GSH) and apolipoprotein E (ApoE) were fabricated to recognize brain microvascular endothelial cells and amyloid beta (Aβ), and reduce tau protein hyperphosphorylation for AD management...Moreover, GSH-ApoE-PC-liposomes benefited the 4 medicines in simultaneously transporting to Aβ-insulted neurons, in functioning against hyperphosphorylated mitogen-activated protein kinases, including p-c-Jun N-terminal protein kinase, p-extracellular signal-regulated protein kinase 1/2 and p-p38, in downregulating tau protein at S202, caspase-3 and interleukin-6, and in upregulating p-cyclic adenosine monophosphate response element-binding protein. GSH-ApoE-PC-liposomes can be promising colloidal carriers in delivering CURC, QU, EGCG and RA to degenerated neural tissue in a controlled manner, targeting pathological factors..."

Journal • Alzheimer's Disease • CNS Disorders • APOE • CASP3 • IL6 • JUN

Molecular insights into phytochemicals-driven break function in tumor microenvironment. (PubMed, J Food Biochem) - "Various phytochemicals, such as curcumin, Epigallocatechin Gallate (EGCG), resveratrol, plumbagin, genistein, and others, have been identified with modulatory effect on TME...The primary objective of this review is to provide a better knowledge about the role of TME in cancer progression and development, focusing on the different targets which can be used for therapeutic approach, and then to give a brief account on some known phytochemicals to date, which have shown remarkable TME modulatory effects. PRACTICAL APPLICATIONS: For the use of phytochemicals as therapeutics, it is highly recommended that their precise target should be known; therefore studies should be encouraged such that the effects of these phytochemicals can be evaluated on the individual cellular level like how the phytochemical is targeting the tumor-associated macrophage, or any other cell residing in the tumor microenvironment (TME), and the compound should target a specific component of TME to avoid..."

Biomarker • Journal • Review • Tumor microenvironment • Oncology

Candidate Anti-COVID-19 Medicinal Plants from Ethiopia: A Review of Plants Traditionally Used to Treat Viral Diseases. (PubMed, Evid Based Complement Alternat Med) - "Lycorine, gingerol shogaol, resveratrol, rhoifolin, oleanolic acid, kaempferol, rosmarinic acid, almond oil, ursolic acid, hederagenin, nigellidine, α-hederin, apigenin, nobiletin, tangeretin, chalcone, hesperidin, epigallocatechin gallate, allicin, diallyl trisulfide, ajoene, aloenin, artemisinin, glucobrassicin, curcumin, piperine, flavonoids, anthraquinone, hydroxychloroquine, and jensenone were some of them. The Ethiopian traditional knowledge applies a lot of medicinal plants to treat different viral infections. Reports of the chemical components of many of them confirm that they can be promising to fight COVID-19."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Green Tea Polyphenol Catechins Inhibit Coronavirus Replication and Potentiate the Adaptive Immunity and Autophagy-Dependent Protective Mechanism to Improve Acute Lung Injury in Mice. (PubMed, Antioxidants (Basel)) - "We found that catechins containing 32.8% epigallocatechin gallate, 15.2% epicatechin gallate, 13.2 epicatechin, 10.8% epigallocatechin, 10.4% gallocatechin, and 4.4% catechin directly inhibited SARS-CoV replication at sub-micromolecular concentrations...Pretreatment of autophagy inhibitor 3-Methyladenine reversed the inhibiting effects of catechins on the cytokines and oxidative stress levels and ALI. In conclusion, our data indicated that catechins directly inhibited SARS-CoV replication, potentiated the CD25/CD69/CD94/CD8 T lymphocytes-mediated adaptive immunity and attenuated lipopolysaccharide-induced ALI and cytokine storm by PI3K/AKT/mTOR-signaling-mediated autophagy, which may be applied to prevent and/or treat SARS-CoV infection."

Journal • Preclinical • Acute Lung Injury • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • ATG12 • ATG5 • BECN1 • CD69 • CD8 • IL2RA

Polyphenols of the Mediterranean Diet and Their Metabolites in the Prevention of Colorectal Cancer. (PubMed, Molecules) - "Due to the high prevalence of intestinal cancer (ranking second in causing morbidity and mortality), this review is focused on the beneficial effects of selected dietary phytophenols, largely present in Mediterranean cooking: apigenin, curcumin, epigallocatechin gallate, quercetin-rutine, and resveratrol...Perspectives are discussed in terms of microbiome-dependency of the brain-second brain axis. The emergence of polyphenol formulations may strengthen the efficiency of the Mediterranean diet in the prevention of cancer."

Journal • Review • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor