Silymarin (Milk Thistle) silibinin / IL6 Cancer Research Results

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↓, IL6↓">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)
IL6, Interleukin-6: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
Interleukin-6 (IL-6) is a cytokine that plays a significant role in inflammation and the immune response. It is produced by various cell types, including T cells, B cells, macrophages, and fibroblasts.
IL-6 can promote tumor cell proliferation and survival. Many cancer cells produce IL-6, which can create an autocrine loop that supports their growth.
IL-6 is a high-value inflammatory biomarker in cancer, reporting cytokine burden, catabolic stress, and STAT3-linked survival signaling. While not tumor-specific, elevated and rising IL-6 strongly predicts poor prognosis and limited treatment tolerance, making it an important system-state indicator alongside CRP and ferritin.


Scientific Papers found: Click to Expand⟱
3328- SIL,    Modulatory effect of silymarin on inflammatory mediators in experimentally induced benign prostatic hyperplasia: emphasis on PTEN, HIF-1α, and NF-κB
- in-vivo, BPH, NA
*NF-kB↓, *Hif1a↓, *PTEN↑, *Weight↓, *NO↓, *IL6↓, *IL8↓, *COX2↓, *iNOS↓,
3323- SIL,    Anticancer therapeutic potential of silibinin: current trends, scope and relevance
- Review, Var, NA
Inflam↓, angioG↓, antiOx↑, TumMeta↓, TumCP↓, TumCCA↑, TumCD↑, α-SMA↓, p‑Akt↓, p‑STAT3↓, COX2↓, IL6↓, MMP2↓, HIF-1↓, Snail↓, Slug↓, Zeb1↓, NF-kB↓, p‑EGFR↓, JAK2↓, PI3K↓, PD-L1↓, VEGF↓, CDK4↓, CDK2↓, cycD1/CCND1↓, E2Fs↓,
3318- SIL,    Pharmaceutical prospects of Silymarin for the treatment of neurological patients: an updated insight
- Review, AD, NA - Review, Park, NA
*hepatoP↑, *neuroP↑, *TLR4↓, *TNF-α↓, *IL1β↓, *NF-kB↓, *memory↑, *cognitive↑, *NRF2↑, *HO-1↑, *ROS↓, *Akt↑, *mTOR↑, *SOD↑, *Catalase↑, *GSH↑, *IL10↑, *IL6↑, *NO↓, *MDA↓, *AChE↓, *MAPK↓, *BDNF↑,
4206- SIL,    Silymarin ameliorates experimentally induced depressive like behavior in rats: Involvement of hippocampal BDNF signaling, inflammatory cytokines and oxidative stress response
- in-vivo, NA, NA
*BDNF↑, *5HT↑, *antiOx↑, *IL6↓, *TNF-α↓, *Mood↑,
4205- SIL,    The Therapeutic Effect of Silymarin and Silibinin on Depression and Anxiety Disorders and Possible Mechanism in the Brain: A Systematic Review
- Review, AD, NA
*BDNF↑, *5HT↑, *MDA↓, *GSH↑, *SOD↑, *Catalase↑, *IL6↓, *IL1β↓,
3648- SIL,    Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years
- Review, NA, NA
*antiOx↑, *Inflam↓, *lipid-P↓, *necrosis↓, *hepatoP↑, *IL1↓, *IL6↓, *TNF-α↓, *IFN-γ↓, MAPK↓, Apoptosis↑, Cyt‑c↑, Casp3↑, Casp9↑, *PPARγ↑, *GLUT4↑, *HSPs↓, *HSP27↑, *Trx↑, *SIRT1↑, *ALAT↓, *GSH↑, *lipid-P↓, *TNF-α↓, TumCG↓, P21↑, CDK4↑,
3307- SIL,    Flavolignans from Silymarin as Nrf2 Bioactivators and Their Therapeutic Applications
- Review, Var, NA
*NRF2↑, *antiOx↑, *chemoP↑, *Inflam↓, *BioAv↑, eff↑, *NQO1↑, TNF-α↓, IL6↓, *GSH↑, *ROS↓, *MDA↓, eff↑, *hepatoP↑, *GPx↑, *SOD↑, *Catalase↑, *HO-1↑, *neuroP↑,
3301- SIL,    Critical review of therapeutic potential of silymarin in cancer: A bioactive polyphenolic flavonoid
- Review, Var, NA
Inflam↓, TumCCA↑, Apoptosis↓, TumMeta↓, TumCG↓, angioG↓, chemoP↑, radioP↑, p‑ERK↓, p‑p38↓, p‑JNK↓, P53↑, Bcl-2↓, Bcl-xL↓, TGF-β↓, MMP2↓, MMP9↓, E-cadherin↑, Wnt↓, Vim↓, VEGF↓, IL6↓, STAT3↓, *ROS↓, IL1β↓, PGE2↓, CDK1↓, CycB/CCNB1↓, survivin↓, Mcl-1↓, Casp3↑, Casp9↑, cMyc↓, COX2↓, Hif1a↓, CXCR4↓, CSCs↓, EMT↓, N-cadherin↓, PCNA↓, cycD1/CCND1↓, ROS↑, eff↑, eff↑, eff↑, HER2/EBBR2↓,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 2,   Casp9↑, 2,   Cyt‑c↑, 1,   p‑JNK↓, 1,   MAPK↓, 1,   Mcl-1↓, 1,   p‑p38↓, 1,   survivin↓, 1,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 1,   CDK4↓, 1,   CDK4↑, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 2,   E2Fs↓, 1,   P21↑, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 1,   p‑ERK↓, 1,   PI3K↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   TumCG↓, 2,   Wnt↓, 1,  

Migration ⓘ

E-cadherin↑, 1,   MMP2↓, 2,   MMP9↓, 1,   N-cadherin↓, 1,   Slug↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TumCP↓, 1,   TumMeta↓, 2,   Vim↓, 1,   Zeb1↓, 1,   α-SMA↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   p‑EGFR↓, 1,   HIF-1↓, 1,   Hif1a↓, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CXCR4↓, 1,   IL1β↓, 1,   IL6↓, 3,   Inflam↓, 2,   JAK2↓, 1,   NF-kB↓, 1,   PD-L1↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 5,  

Clinical Biomarkers ⓘ

p‑EGFR↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 3,   PD-L1↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   radioP↑, 1,  
Total Targets: 71

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   Catalase↑, 3,   GPx↑, 1,   GSH↑, 4,   HO-1↑, 2,   lipid-P↓, 2,   MDA↓, 3,   NQO1↑, 1,   NRF2↑, 2,   ROS↓, 3,   SOD↑, 3,   Trx↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↑, 1,   iNOS↓, 1,   MAPK↓, 1,   necrosis↓, 1,  

Protein Folding & ER Stress ⓘ

HSP27↑, 1,   HSPs↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↑, 1,   PTEN↑, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,   NO↓, 2,  

Barriers & Transport ⓘ

GLUT4↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IFN-γ↓, 1,   IL1↓, 1,   IL10↑, 1,   IL1β↓, 2,   IL6↓, 4,   IL6↑, 1,   IL8↓, 1,   Inflam↓, 2,   NF-kB↓, 2,   TLR4↓, 1,   TNF-α↓, 4,  

Synaptic & Neurotransmission ⓘ

5HT↑, 2,   AChE↓, 1,   BDNF↑, 3,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   IL6↓, 4,   IL6↑, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   cognitive↑, 1,   hepatoP↑, 3,   memory↑, 1,   Mood↑, 1,   neuroP↑, 2,   Weight↓, 1,  
Total Targets: 52

Scientific Paper Hit Count for: IL6, Interleukin-6
8 Silymarin (Milk Thistle) silibinin
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#:158  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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