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EGCG (Epigallocatechin Gallate) is found in green tea. 100 times more effective than Vitamin C and 25 times more effective than Vitamin E at protecting cells from damage associated with oxidative stress. EGCG Epigallocatechin Gallate (Green Tea) -Catechin Summary: 1. Concentration is a factor that could determine whether green tea polyphenols act as antioxidants or pro-oxidants. 2. Poor bioavailability: taking EGCG capsules without food was better. 3. Cancer dosage 4g/day (2g twice per day)? with curcumin may help (another ref says 700–2100 mg/d) 4. EGCG is susceptible to oxidative degradation. 5. “As for the pH level, the acidic environments enhance the stability of EGCG”. 6. “EGCG may enhance nanoparticle uptake by tumor cells” 7. Might be iron chelator (removing iron from cancer cells) 8. Claimed as synergistic effect with chemotherapy ( cisplatin, bleomycin, gemcitabine. 9. May suppress glucose metabolism, interfere with VEGF, downregulate NF-κB and MMP-9, down-regulation of androgen-regulated miRNA-21. 10. Take with red pepper powder, Capsicum ratio 25:1 (based on half life, they did every 4 hr) (chili pepper vanilloid capsaicin). 11. EGCG mediated ROS formation can upregulate CTR1 expression via the ERK1/2/NEAT1 pathway, which can increase the intake of chemotherapeutic drugs such as cisplatin in NSCLC cells and act as a chemosensitizer [58] 12. Matcha green tea has highest EGCG (2-3X) because consuming leaf. 13. EGCG is an ENOX2 inhibitor. 14. Nrf2 activator in both cancer and normal cells. This example of lung cancer show both directions in different cell lines, but both toward optimim level. Biological activity, EGCG has been reported to exhibit a range of effects, including: Antioxidant activity: 10-50 μM Anti-inflammatory activity: 20-50 μM Anticancer activity: 50-100 μM Cardiovascular health: 20-50 μM Neuroprotective activity: 10-50 μM Drinking a cup (or two cups) of green tea (in which one might ingest roughly 50–100 mg of EGCG from brewed tea) generally results in peak plasma EGCG concentrations in the range of approximately 0.1 to 0.6 μM. With higher, supplement-type doses (e.g., oral doses in the 500 mg–800 mg range that are sometimes studied for clinical benefits), peak plasma concentrations in humans can reach the low micromolar range, often reported around ~1–2 μM and in some cases up to 5 μM. Reported values can range from about 25–50 mg of EGCG per gram of matcha powder. In cases where the matcha is exceptionally catechin-rich, the content could reach 200–250 mg or more in 5 g. -Peak plasma concentration roughly 1 to 2 hours after oral ingestion. -Elimination half-life of EGCG in plasma is commonly reported to be in the range of about 3 to 5 hours. Supplemental EGCG Dose (mg) ≈ Peak Plasma EGCG (µM) ~50 mg ≈ 0.1–0.3 µM ~100 mg ≈ 0.2–0.6 µM ~250 mg ≈ 0.5–1.0 µM ~500 mg ≈ 1–2 µM ~800 mg or higher ≈ 1–5 µM 50mg of EGCG in 1g of matcha tea(1/2 teaspoon) Studies on green tea extracts have employed doses roughly equivalent to 300–800 mg/day of EGCG. Excessive doses can cause liver toxicity in some cases. Methods to improve bioavailability -Lipid-based carriers or nanoemulsions -Polymer-based nanoparticles or encapsulation -Co-administration with ascorbic acid (vitamin C) -Co-administration of adjuvants like piperine (perhaps sunflower lecithin and chitosan) -Using multiple smaller doses rather than one large single dose. -Taking EGCG on an empty stomach or under fasting conditions, or aligning dosing with optimal pH conditions in the GI tract, may improve its absorption.(acidic environment is generally more favorable for its stability and absorption). – EGCG is more stable under acidic conditions. In the stomach, where the pH is typically around 1.5 to 3.5, EGCG is less prone to degradation compared to the more neutral or basic environments of the small intestine. - At neutral (around pH 7) or alkaline pH, EGCG undergoes auto-oxidation, reducing the effective concentration available for absorption. – Although the stomach’s acidic pH helps maintain EGCG’s stability, most absorption occurs in the small intestine, where the pH is closer to neutral. – To counterbalance the inherent instability in the intestine, strategies such as co-administration of pH-modifying agents (like vitamin C) are sometimes used. These agents help to maintain a slightly acidic environment in the gut microenvironment, potentially improving EGCG stability during its transit and absorption. – The use of acidifiers or buffering agents in supplements may help preserve EGCG until it reaches the absorption sites. -Note half-life 3–5 hours. - low BioAv 1%? despite its limited absorption, it is rapidly disseminated throughout the body Pathways: - induce ROS production - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx, - Does NOT Lower AntiOxidant defense in Cancer Cells: NRF2↑">NRF2↑, TrxR↓**, SOD, GSH Catalase HO1 GPx - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑">NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓ - reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, - inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓, - inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi↓, GLi1↓, CD133↓, CD24↓, β-catenin↓, n-myc↓, Notch↓, OCT4↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, - SREBP (related to cholesterol). - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective(possible damage at high dose), CardioProtective, - Selectivity: Cancer Cells vs Normal Cells
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| Source: TCGA |
| Type: Antiapoptotic |
| Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. Thought of as "Master Regulator" of antioxidant response. -One way to estimate Nrf2 induction is through the expression of NQO1. NQO1, the most potent inducer: SFN 0.2 μM, quercetin (2.5 μM), curcumin (2.7 μM), Silymarin (3.6 μM), tamoxifen (5.9 μM), genistein (6.2 μM ), beta-carotene (7.2μM), lutein (17 μM), resveratrol (21 μM), indol-3-carbinol (50 μM), chlorophyll (250 μM), alpha-cryptoxanthin (1.8 mM), and zeaxanthin (2.2 mM) 1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects. 2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death. 3. However there are some cases where increasing Nrf2 paradoxically causes an increase in ROS (cancer cells). Such as cases of Mitochondial overload, signal crosstalk, reductive stress -In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies. -Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate. Decreased Nrf2 expression: Skine, Liver, Pancreatic. -Nrf2 is a cytoprotective transcription factor which demonstrated both a negative effect as well as a positive effect on cancer - "promotes Nrf2 translocation from the cytoplasm to the nucleus," means facilitates the movement of Nrf2 into the nucleus, thereby enhancing the cell's antioxidant and cytoprotective responses. -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1. Nrf2 Inhibitors and Activators Nrf2 Inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api - potent Nrf2 inducers from plants include sulforaphane, curcumin, EGCG, resveratrol, caffeic acid phenethyl ester, wasabi, cafestol and kahweol (coffee), cinnamon, ginger, garlic, lycopene, rosemany Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue. – In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis. – In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity. – This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming. – Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies. – High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types. – While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression. NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS). -Brusatol: most cited natural inhibitors of Nrf2. -Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent. -Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: Dose and context dependent . -Oridonin: -Wogonin: although its effects might be cell‑ and dose‑specific. - Withaferin A |
| 4881- | CUR, | SFN, | RES, | EGCG, | Lyco | An update of Nrf2 activators and inhibitors in cancer prevention/promotion |
| - | Review, | Var, | NA |
| 3201- | EGCG, | Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential |
| - | Review, | NA, | NA |
| 3209- | EGCG, | Epigallocatechin gallate upregulates NRF2 to prevent diabetic nephropathy via disabling KEAP1 |
| - | in-vitro, | Diabetic, | NA |
| 3210- | EGCG, | Protective effect of epigallocatechin-3-gallate (EGCG) via Nrf2 pathway against oxalate-induced epithelial mesenchymal transition (EMT) of renal tubular cells |
| - | in-vitro, | Nor, | NA |
| 3211- | EGCG, | Antioxidation Function of EGCG by Activating Nrf2/HO-1 Pathway in Mice with Coronary Heart Disease |
| - | in-vivo, | NA, | NA |
| 1974- | EGCG, | Protective Effect of Epigallocatechin-3-Gallate in Hydrogen Peroxide-Induced Oxidative Damage in Chicken Lymphocytes |
| - | in-vitro, | Nor, | NA |
| 3213- | EGCG, | Rad, | Epigallocatechin-3-gallate Enhances Radiation Sensitivity in Colorectal Cancer Cells Through Nrf2 Activation and Autophagy |
| - | in-vitro, | CRC, | HCT116 |
| 3221- | EGCG, | EGCG upregulates phase-2 detoxifying and antioxidant enzymes via the Nrf2 signaling pathway in human breast epithelial cells |
| - | in-vitro, | Nor, | MCF10 |
| 3214- | EGCG, | EGCG-induced selective death of cancer cells through autophagy-dependent regulation of the p62-mediated antioxidant survival pathway |
| - | in-vitro, | Nor, | MRC-5 | - | in-vitro, | Cerv, | HeLa | - | in-vitro, | Nor, | HEK293 | - | in-vitro, | BC, | MDA-MB-231 | - | in-vitro, | CRC, | HCT116 |
| 3215- | EGCG, | Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer |
| - | in-vitro, | NSCLC, | A549 | - | in-vitro, | NSCLC, | H1299 |
| 3216- | EGCG, | Epigallocatechin-3-gallate suppresses hemin-aggravated colon carcinogenesis through Nrf2-inhibited mitochondrial reactive oxygen species accumulation |
| - | NA, | Colon, | Caco-2 |
| 3217- | EGCG, | Epigallocatechin-3-gallate promotes angiogenesis via up-regulation of Nfr2 signaling pathway in a mouse model of ischemic stroke |
| - | in-vivo, | Stroke, | NA |
| 3219- | EGCG, | Nano-chemotherapeutic efficacy of (−) -epigallocatechin 3-gallate mediating apoptosis in A549 cells: Involvement of reactive oxygen species mediated Nrf2/Keap1signaling |
| - | in-vitro, | Lung, | A549 |
| 3220- | EGCG, | Dual Roles of Nrf2 in Cancer |
| - | in-vitro, | Lung, | A549 |
| 3212- | EGCG, | EGCG maintained Nrf2-mediated redox homeostasis and minimized etoposide resistance in lung cancer cells |
| - | in-vitro, | Lung, | A549 | - | in-vivo, | Lung, | NCIH23 |
| 20- | EGCG, | Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer |
| - | in-vivo, | Liver, | NA | - | in-vivo, | Tong, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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