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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↑, TrxR↓**, SOD, GSH Catalase HO1 GPx - Raises AntiOxidant defense in Normal Cells: ROS↓, 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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| A bioenhancer is an agent capable of enhancing bioavailability and efficacy of a drug with which it is co-administered Query Database for BioEnhancers but the bioenhancers mainly show up under the target notes Bioenhancers - piperine and quercetin are considered bio-enhancers - genistein Piperine act by suppressing P-gp and cytochrome P450 enzymes, which counteract the metabolism of rifampicin via these proteins, thus enhancing the oral bioavailability of rifampicin. It also decreases the intestinal production of glucuronic acid, thus allowing more substances to enter the body in active form. It was found to increase the bioavailability of various drugs from 30% to 200%.[25] Table 1: Published research on bioenhancer effect of piperine with various medicines Drug Studied in Reference Antimicrobial agents Rifampicin In vitro Balakrishnan et al, 2001[11] Isoniazid Rabbits Karan et al, 1998 [12] Pefl oxacin Mountain Gaddi goats Madhukar et al, 2008[13] Tetracycline Rats Atal et al, 1980[14] Sulfadiazine Rats and dogs Atal et al, 1980[14] Oxytetracycline Poultry birds Singh et al, 2005[15] Ampicillin Rabbits Janakiraman and Manavalan, 2008[16] Norfl oxacin Rabbits Janakiraman and Manavalan, 2008 [16] Nevirapine Adult males Kasibhatta et al, 2007 [17] Metronidazole In vitro Singh et al, 2010[18] Analgesics Diclofenac sodium Albino mice Pooja et al, 2007[19] Pentazocine Albino mice Pooja et al, 2007[19] Nimesulide Mice Gupta et al, 1998[20] Antiepileptics Carbamazepine In vitro Pattanaik et al, 2009 [21] Phenytoin Human volunteers Bano et al, 1987[22] Pentobarbitone Rats Majumdar et al, 1990[23] Other drugs Propranolol In vitro Bano et al, 1991 [24] Theophylline In vitro Bano et al, 1991 [24] Nutrients In vitro Pooja et al, 2007 [19 ***Borneol -Borneol is thought to temporarily open tight junctions between endothelial cells, enhancing drug penetration. It may also downregulate efflux transporters such as P-glycoprotein (P-gp), allowing higher intracellular concentrations of co-administered drugs. -presence of urea (as a carrier) increased the aqueous solubility of capsaicin by 3.6-fold compared to pure capsaicin Quercetin is found in citrus fruits and is a dual inhibitor of cytochrome P 3A4 (CYP3A4) and P-gp. Table 2: Effect of quercetin pretreatment/co-treatment on pharmacokinetic parameters of different drugs Drugs combined Increase in pharmacokinetic parametera Cmax AUC ABA Verapamil Two fold Two fold SH Diltiazem SH SH Not known Paclitaxel SH SH T wo fold Digoxin 413% 170% Not known Tamoxifen SH SH 59% Compared to drug in question alone. Cmax, peak plasma concentration; AUC, area under the curve; ABA, absolute bioavailability; SH, significantly higher. Another flavonoid, genistein belongs to the isoflavone class of flavonoids. It is a well-known phytoestrogen. The presence of genistein (10 mg/kg) caused an increase in AUC (54.7%) and a decrease in the total plasma clearance (35.2%) after oral administration of paclitaxel at a dose of 30 mg/kg in rats.[37] Naringin is the major flavonoid glycoside found in grapefruit and makes grapefruit juice taste bitter. Oral naringin (3.3 and 10 mg/kg) was pretreated 30 min before and after intravenous administration of paclitaxel (3 mg/kg), the AUC was significantly improved (40.8% and 49.1% for naringin doses of 3.3 and 10 mg/kg, respectively).[38 Carum carvi/Cuminum cyminum ( Jeera) Carum carvi seeds are a prized culinary herb. Extracts of its parts increased significantly (25%–300%), the bioavailability of a number of classes of drugs, such as antibiotics, antifungals, antivirals, anticancer, cardiovascular, anti-inflammatory/ antiarthritic, anti-TB, antileprosy, antihistaminic/respiratory disorders, corticosteroids, immunosuppressants, and antiulcers. Such extracts either in the presence or absence of piperine have been found to be highly selective in their bioavailability/bioefficacy-enhancing action.[40] Capmul One of the widely used bioenhancers is Capmul MCM C10, a glyceryl monocaprate, produced from edible fats and oils and is commonly used in lip products. In a study in rats, antibiotic ceftriaxone when given concomitantly with capmul, increased the bioavailability of ceftriaxone by 80%.[41] Nitrile glycoside Nitrite glycoside is a bioenhancer for drugs and nutrients. Novel bioactive nitrile glycosides, niaziridin and niazirin is obtained from the leaves, pods, and bark of Moringa oleifera. [42] An immunoenhancing polysaccharide and niaziminin, having structural requirement to inhibit tumor promoter-induced Epstein–Barr virus activation have been reported from the leaves of Moringa.[43,44] It enhances the bioactivity of commonly used antibiotics, such as rifampicin, tetracycline, and ampicillin, and also facilitate the absorption of drugs, vitamins, and nutrients through the gastrointestinal membrane, thus increasing their bioavailability. [41] Niazirin is another bioactive nitrile glycoside belonging to M. oleifera. [45,46] Process of isolation of nitrite glycoside from M. oleifera has been patented (US 6858588) by Khanuja et al in 2004–2005. [42 Mechanism of Action Of Bioenhancers Bioavailability-enhancing activity of natural compounds from the medicinal plants may be attributed to various mechanisms, such as P-gp inhibition activity by flavone, quercetin, and genistein; [51] inhibition of efflux transporters, such as P-gp and breast cancer resistance protein (BCRP),[52,53] by naringin and sinomenine thus preventing drug resistance; DNA receptor binding, modulation of cell signaling transduction, and inhibition of drug efflux pumps[54-56] ; by stimulating leucine amino peptidase and glycyl–glycine dipeptidase activity, thus modulating the cell membrane dynamics related to passive transport mechanism as seen with piperine [57] ; nonspecific mechanisms, such as increased blood supply to the gastrointestinal tract, decreased hydrochloric acid secretion, preventing breakdown of some drugs[6] ; and inhibition of metabolic enzymes participating in the biotransformation of drugs, thus preventing inactivation and elimination of drugs and thereby, increasing their bioavailability. [57-5] |
| 658- | EGCG, | MNPs, | MF, | Laminin Receptor-Mediated Nanoparticle Uptake by Tumor Cells: Interplay of Epigallocatechin Gallate and Magnetic Force at Nano-Bio Interface |
| - | in-vitro, | GBM, | LN229 |
| 649- | EGCG, | CUR, | PI, | Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets |
| - | Review, | Var, | NA |
| 654- | EGCG, | MNPs, | MF, | Characterization of mesenchymal stem cells with augmented internalization of magnetic nanoparticles: The implication of therapeutic potential |
| - | in-vitro, | Var, | NA |
| 657- | EGCG, | MNPs, | MF, | Interaction of poly-l-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells |
| - | in-vitro, | GBM, | U87MG |
| 659- | EGCG, | MNPs, | MF, | Augmented cellular uptake of nanoparticles using tea catechins: effect of surface modification on nanoparticle-cell interaction |
| - | in-vivo, | Nor, | NA |
| 662- | EGCG, | Advanced Nanovehicles-Enabled Delivery Systems of Epigallocatechin Gallate for Cancer Therapy |
| - | Review, | Var, | NA |
| 674- | EGCG, | Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals |
| - | Review, | Var, | 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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