Database Query Results : Silymarin (Milk Thistle) silibinin, , OCT4

SIL, Silymarin (Milk Thistle) silibinin: Click to Expand ⟱
Features:
Silymarin (Milk Thistle) Flowering herb related to daisy and ragweed family.
Silibinin (INN), also known as silybin is the major active constituent of silymarin, a standardized extract of the milk thistle seeds.
-a flavonoid combination of 65–80% of seven flavolignans; the most important of these include silybin, isosilybin, silychristin, isosilychristin, and silydianin. Silybin is the most abundant compound in around 50–70% in isoforms silybin A and silybin B

-Note half-life 6hrs?.
BioAv not soluble in water, low bioAv (1%). 240mg yielded only 0.34ug/ml plasma level. oral administration of SM (equivalent to 120 mg silibinin), total (unconjugated + conjugated) silibinin concentration in plasma was 1.1–1.3 μg/mL, so can not achieve levels used in most in-vitro studies.
Pathways:
- results for both inducing and reducing ROS in cancer cells. In normal cell seems to consistently lower ROS. Reports show both ROS↑ and ROS↓ in cancer models; systemic pro-oxidant effects may require higher exposures than typical oral dosing, but local or combination contexts may differ. (level in GUT could be much higher (800uM).
- ROS↑ related: MMP↓(ΔΨm), Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑,
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓(context-dependent; often stress-activated), Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, uPA↓, VEGF↓, FAK↓, NF-κB↓, CXCR4↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, GRP78↑(ER stress), Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi1↓, β-catenin↓, Notch2↓, 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, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 ROS / redox buffering + mitochondrial protection Often ↑ stress susceptibility; can support apoptosis when survival signaling is blocked ↓ oxidative stress; mitochondrial protection P, R, G Context-selective redox modulation Silymarin is classically cytoprotective/antioxidant in normal tissues (notably liver), while in tumors it can weaken pro-survival adaptation and increase vulnerability to stressors and therapy.
2 Intrinsic apoptosis (mitochondria → caspases) ↑ apoptosis signaling; ↑ caspase activation ↔ minimal activation G Cell death execution Common downstream outcome in cancer models: apoptosis increases after earlier signaling/redox shifts and/or checkpoint disruption.
3 Cell-cycle control (cyclins/CDKs; checkpoints) ↑ arrest (G1/S or G2/M depending on model) ↔ G Cytostasis Typically observed as reduced proliferation with checkpoint engagement; timing usually later than kinase phosphorylation changes.
4 NF-κB inflammatory transcription ↓ NF-κB activity; ↓ inflammatory/pro-survival tone ↔ or protective anti-inflammatory effect R, G Anti-inflammatory / anti-survival transcription NF-κB suppression can reduce tumor-promoting inflammation and blunt stress-adaptive survival programs.
5 JAK/STAT3 axis (incl. PD-L1 / immune escape programs in some models) ↓ STAT3 signaling (context); may ↓ PD-L1 in certain tumor contexts ↔ R, G Reduced survival + immune-evasion signaling Reported to attenuate STAT3-driven tumor programs and, in some contexts, reduce immune-suppressive signaling (model dependent).
6 PI3K → AKT → mTOR survival / growth signaling ↓ PI3K/AKT/mTOR signaling (context) ↔ R, G Growth/survival suppression Reduced PI3K/AKT/mTOR tone increases sensitivity to apoptosis and can reinforce cell-cycle arrest.
7 MAPK re-wiring (ERK/p38/JNK balance) Stress-MAPK shifts; ERK tone often reduced or re-patterned ↔ P, R, G Signal reprogramming Early phosphorylation shifts can precede later gene-expression changes; exact ERK direction is model and dose dependent.
8 Angiogenesis (VEGF and angiogenic factors) ↓ VEGF / angiogenesis outputs ↔ G Anti-angiogenic support Typically reflected in reduced pro-angiogenic expression/secretion and angiogenesis-related phenotypes over longer windows.
9 EMT / invasion / migration programs (incl. TGF-β/Smad-associated EMT in some systems) ↓ EMT markers; ↓ migration/invasion ↔ G Anti-invasive phenotype Often presents as restoration of epithelial markers and suppression of migration/invasion assays; commonly a later phenotype-level outcome.
10 Xenobiotic handling (Phase I/II enzymes; cytoprotection / chemoprevention framing) May alter carcinogen activation/detox balance ↑ detox / cytoprotection against xenobiotics G Chemopreventive protection A key “dual strategy” theme: protection of normal tissue from toxins/therapy while modulating tumor response pathways.
11 Drug resistance / efflux (MDR phenotype; P-gp-related resistance in some models) May ↓ functional MDR and ↑ chemo sensitivity (context) ↔ R, G Chemo-sensitization support Reported synergy with chemotherapy in resistant tumor settings; transporter direction can be context-specific, so present as “reported to reduce functional resistance” rather than a universal single-transporter claim.
12 Immune microenvironment signaling (cytokines / macrophage recruitment in some models) May ↓ pro-tumor cytokine programs and recruitment signals (context) ↔ G Anti-inflammatory tumor microenvironment shift Immune-modulatory effects are increasingly discussed, but they are more model-dependent and typically show on longer time scales.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (primary/physical–chemical effects; rapid signaling / phosphorylation shifts)
  • R: 30 min–3 hr (redox signaling + acute stress-response signaling)
  • G: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)
OCT4, Octamer-binding transcription factor 4: Click to Expand ⟱
Source:
Type:
POU5F1 is a gene that encodes a transcription factor also known as Oct4.
OCT4 (Octamer-binding transcription factor 4) is a transcription factor that plays a crucial role in maintaining the pluripotency and self-renewal of embryonic stem cells. It is part of the core regulatory network that governs stem cell identity and is essential for the early stages of development.
OCT4 is often expressed in cancer stem cells, which are a subpopulation of cells within tumors that possess the ability to self-renew and drive tumorigenesis. The presence of OCT4 in these cells is associated with increased tumor aggressiveness and resistance to conventional therapies.
Scientific Papers found: Click to Expand⟱
3314- SIL,    Silymarin: Unveiling its pharmacological spectrum and therapeutic potential in liver diseases—A comprehensive narrative review
- Review, NA, NA
*antiOx↑, silymarin, demonstrating remarkable antioxidant and hepatoprotective properties in extensive preclinical investigations.
*hepatoP↑, It can protect healthy liver cells or those that have not yet sustained permanent damage by reducing oxidative stress and mitigating cytotoxicity.
*Half-Life↑, The main ingredient in silymarin, silibinin, normally takes two to four hours to reach its peak plasma concentration after oral consumption, and it has a 6‐hour plasma half‐life
*ROS↓, silibinin has potent anti‐ROS qualities,
*GSH↑, silymarin, the precursor to silibinin, can increase glutathione production in the liver and hence increase the liver tissues' antioxidant capacity
*hepatoP↑, silymarin, the precursor to silibinin, can increase glutathione production in the liver and hence increase the liver tissues' antioxidant capacity
*lipid-P↓,
*TNF-α↓, inhibit the production of pro‐inflammatory cytokines, such as TNF‐α, IFN‐γ, IL‐2, and IL‐4, which are crucial in the inflammatory cascade
*IFN-γ↓,
*IL2↓,
*IL4↓,
*NF-kB↓, Silymarin's mechanism involves suppressing NF‐κB activation,
*iNOS↓, It downregulates inflammatory mediators like interleukins, TNF‐α, and iNOS, which are involved in various diseases.
*OATPs↓, Its inhibition of transporters, including OATPs and OCTs, may also affect members of the solute carrier family
*OCT4↓,
*Inflam↓, Silymarin may have anti‐inflammatory properties that limit the production of inflammatory mediators like NF‐B and inflammatory metabolites like prostaglandin E2 (PGE2)
*PGE2↓,
MMPs↓, Silymarin significantly inhibits matrix metalloproteinases (MMPs), essential for cancer metastasis,
VEGF↓, Additionally, silymarin down‐regulates VEGF expression, contributing to anti‐angiogenic effects, and has the potential to reverse STAT‐3‐associated cancer drug resistance.
angioG↓,
STAT3↓,
*ALAT↓, The research revealed improved liver function as seen by lower levels of ALT, AST, and alkaline phosphatase, as well as a considerably lower likelihood of developing DILI four weeks after starting silymarin treatment
*AST↓,
Dose↝, The suggested dosage of silymarin has been used in clinical trials for up to 48 weeks at a dose of 2100 mg/day and for up to 4 years at a dose of up to 420 mg/day.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Proliferation, Differentiation & Cell State ⓘ

STAT3↓, 1,  

Migration ⓘ

MMPs↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   VEGF↓, 1,  

Drug Metabolism & Resistance ⓘ

Dose↝, 1,  
Total Targets: 5

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   GSH↑, 1,   lipid-P↓, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,  

Cell Death ⓘ

iNOS↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

OCT4↓, 1,  

Barriers & Transport ⓘ

OATPs↓, 1,  

Immune & Inflammatory Signaling ⓘ

IFN-γ↓, 1,   IL2↓, 1,   IL4↓, 1,   Inflam↓, 1,   NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

Half-Life↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,  

Functional Outcomes ⓘ

hepatoP↑, 2,  
Total Targets: 19

Scientific Paper Hit Count for: OCT4, Octamer-binding transcription factor 4
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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:154  Target#:508  State#:%  Dir#:%
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