condition found tbRes List
EGCG, EGCG (Epigallocatechin Gallate): Click to Expand ⟱
Features:
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


Gli1, glioma-associated oncogene homolog 1: Click to Expand ⟱
Source:
Type: HH
Gli family zinc-finger transcription factors; GLI1‐dependent target genes (CyclinD1, Bcl‐2, Foxm1)

Glioma-associated oncogene homolog 1 (GLI1) is a transcription factor that plays a significant role in the Hedgehog signaling pathway, which is crucial for cell growth, differentiation, and tissue patterning during embryonic development.
GLI1 can promote tumor growth and survival by regulating the expression of genes involved in cell proliferation, apoptosis, and angiogenesis. Its overexpression has been associated with aggressive tumor behavior and poor prognosis in several cancer types.
ts overexpression is often associated with aggressive tumor behavior, poor prognosis, and resistance to therapy
Scientific Papers found: Click to Expand⟱
3245- EGCG,    (−)-Epigallocatechin-3-gallate protects PC12 cells against corticosterone-induced neurotoxicity via the hedgehog signaling pathway
- in-vitro, Nor, PC12
*neuroP↑, EGCG-mediated neuroprotective effects, as well as upregulation of the Shh pathway
*Shh↑,
*Gli1↑, reversed the decrease in the levels of Shh, Gli1 and N-myc mRNA (P<0.05; Fig. 3B) and expression of N-myc protein (P<0.05; Fig. 3C) induced by 400 µM CORT.
*n-MYC↑,
*Dose↝, Higher doses of EGCG exhibit pro-oxidant and pro-apoptotic effects, whereas lower doses of EGCG have neuroprotective effects

651- EGCG,    Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications
ROS↑, mounting evidence that EGCG can stimulate ROS production, which in turn leads to the phosphorylation and activation of AMPK
p‑AMPK↑,
mTOR↓,
FAK↓,
Smo↓,
Gli1↓,
HH↓,
TumCMig↓,
TumCI↓,
NOTCH↓,
JAK↓,
STAT↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
Casp9↑,

21- EGCG,    Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice
- in-vivo, Liver, NA
HH↓,
PTCH1↓,
Smo↓,
Gli1↓,

22- EGCG,    Inhibition of sonic hedgehog pathway and pluripotency maintaining factors regulate human pancreatic cancer stem cell characteristics
- in-vitro, PC, CD133+ - in-vitro, PC, CD44+ - in-vitro, PC, CD24+ - in-vitro, PC, ESA+
HH↓,
Smo↓,
PTCH1↓,
PTCH2↓,
Gli1↓,
GLI2↓,
Gli↓,
Bcl-2↓,
XIAP↓,
Shh↓,
EMT↓,
survivin↓,
Nanog↓,
Casp3↑,
Casp7↑,

23- EGCG,    (-)-Epigallocatechin-3-gallate induces apoptosis and suppresses proliferation by inhibiting the human Indian Hedgehog pathway in human chondrosarcoma cells
- in-vitro, Chon, SW1353 - in-vitro, Chon, CRL-7891
HH↓,
Gli1↓,
PTCH1↓,
Bcl-2↓,
BAX↑,

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
HH↓,
Gli1↓,
Smo↓,
TNF-α↓,
COX2↓, EGCG inhibits cyclooxygenase-2 without affecting COX-1 expression at both the mRNA and protein levels, in androgen-sensitive LNCaP and androgen-insensitive PC-3
*antiOx↑, EGCG is a well-known antioxidant and it scavenges most free radicals, such as ROS and RNS
Hif1a↓,
NF-kB↓,
VEGF↓,
STAT3↓,
Bcl-2↓,
P53↑, EGCG activates p53 in human prostate cancer cells
Akt↓,
p‑Akt↓,
p‑mTOR↓,
EGFR↓,
AP-1↓,
BAX↑,
ROS↑, apoptosis was convoyed by ROS production and caspase-3 cleavage
Casp3↑,
Apoptosis↑,
NRF2↑, pancreatic cancer cells via inducing cellular reactive oxygen species (ROS) accumulation and activating Nrf2 signaling
*H2O2↓, EGCG plays a role in the inhibition of H2O2 and NO production in human skin [10].
*NO↓, EGCG plays a role in the inhibition of H2O2 and NO production in human skin [10].
*SOD↑, fig 2
*Catalase↑, fig 2
*GPx↑, fig 2
*ROS↓, fig 2


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   p‑Akt↓,1,   p‑AMPK↑,1,   AP-1↓,1,   Apoptosis↑,1,   BAX↑,3,   Bcl-2↓,4,   Bcl-xL↓,1,   Casp3↑,2,   Casp7↑,1,   Casp9↑,1,   COX2↓,1,   EGFR↓,1,   EMT↓,1,   FAK↓,1,   Gli↓,1,   Gli1↓,5,   GLI2↓,1,   HH↓,5,   Hif1a↓,1,   JAK↓,1,   mTOR↓,1,   p‑mTOR↓,1,   Nanog↓,1,   NF-kB↓,1,   NOTCH↓,1,   NRF2↑,1,   P53↑,1,   PTCH1↓,3,   PTCH2↓,1,   ROS↑,2,   Shh↓,1,   Smo↓,4,   STAT↓,1,   STAT3↓,1,   survivin↓,1,   TNF-α↓,1,   TumCI↓,1,   TumCMig↓,1,   VEGF↓,1,   XIAP↓,1,  
Total Targets: 41

Results for Effect on Normal Cells:
antiOx↑,1,   Catalase↑,1,   Dose↝,1,   Gli1↑,1,   GPx↑,1,   H2O2↓,1,   n-MYC↑,1,   neuroP↑,1,   NO↓,1,   ROS↓,1,   Shh↑,1,   SOD↑,1,  
Total Targets: 12

Scientific Paper Hit Count for: Gli1, glioma-associated oncogene homolog 1
6 EGCG (Epigallocatechin Gallate)
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:73  Target#:124  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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