Silymarin (Milk Thistle) silibinin / TNF-α 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↓">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↓">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)

TNF-α, TNF-α: Click to Expand ⟱

Source: HalifaxProj (block)

Type:

Tumor Necrosis Factor-alpha (TNF-α) is a cytokine that plays a complex role in cancer biology. It is primarily produced by activated macrophages and is involved in systemic inflammation. TNF-α is a pro-inflammatory cytokine that can promote inflammation, which is a known factor in cancer development.
Overall, the expression of TNF-α in cancers is often linked to inflammation, tumor progression, and the tumor microenvironment.

Scientific Papers found: Click to Expand⟱

3320-

SIL,

Neuroprotective Potential of Silymarin against CNS Disorders: Insight into the Pathways and Molecular Mechanisms of Action

Review,

AD,

*hepatoP↑, *neuroP↑, *ROS↓, *β-Amyloid↓, *Inflam↓, *Aβ↓, *NF-kB↓, *TNF-α↓, *TNF-β↓, *iNOS↓, *NO↓, *COX2↓,

3319-

SIL,

Silymarin and neurodegenerative diseases: Therapeutic potential and basic molecular mechanisms

Review,

AD,

Review,

Park,

Review,

Stroke,

*neuroP↑, *ROS↓, *Inflam↓, *Apoptosis↓, *BBB?, *tau↓, *NF-kB↓, *IL1β↓, *TNF-α↓, *IL4↓, *MAPK↓, *memory↑, *cognitive↑, *Aβ↓, *ROS↓, *lipid-P↓, *GSH↑, *MDA↓, *SOD↑, *Catalase↑, *AChE↓, *BChE↓, *p‑ERK↓, *p‑JNK↓, *p‑p38↓, *GutMicro↑, *COX2↓, *iNOS↓, *TLR4↓, *neuroP↑, *Strength↑, *AMPK↑, *MMP↑, *necrosis↓, *NRF2↑, *HO-1↑,

3318-

SIL,

Pharmaceutical prospects of Silymarin for the treatment of neurological patients: an updated insight

Review,

AD,

Review,

Park,

*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↑,

4207-

SIL,

Silymarin sex-dependently improves cognitive functions and alters TNF-α, BDNF, and glutamate in the hippocampus of mice with mild traumatic brain injury

*TNF-α↓, *BDNF↑, *cognitive↑,

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,

100mg/kg and 200mg/kg, by per oral

Wistar rats

*BDNF↑, *5HT↑, *antiOx↑, *IL6↓, *TNF-α↓, *Mood↑,

4203-

SIL,

Unlocking the Neuroprotective Potential of Silymarin: A Promising Ally in Safeguarding the Brain from Alzheimer’s Disease and Other Neurological Disorders

Review,

NA,

*MAPK↝, *AMPK↝, *NF-kB↓, *mTOR↝, *PI3K↝, *Akt↝, *BioAv↝, *memory↑, *BDNF↑, *TNF-α↓,

3315-

SIL,

Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats

in-vivo,

Nor,

rats

neuroP↑, *NRF2↑, *HO-1↑, *lipid-P↓, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, *NF-kB↓, *TNF-α↓, *JNK↓, *Bcl-2↑, *BAX↑,

3648-

SIL,

Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

Review,

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↑,

3646-

SIL,

"Silymarin", a promising pharmacological agent for treatment of diseases

Review,

NA,

*P-gp↓, *Inflam↓, *hepatoP↑, *antiOx↑, *GSH↑, *BioAv↑, *SOD↑, *IFN-γ↓, *IL4↓, *IL10↓, *Half-Life↓, *TNF-α↓, *ALAT↓, *AST↓, Akt↓, chemoP↑, β-catenin/ZEB1↓, TumCP↓, MMP↓, Cyt‑c↑, *RenoP↑, *BBB↑,

3295-

SIL,

Hepatoprotective effect of silymarin

Review,

NA,

*hepatoP↑, *ROS↓, *GSH↑, *BioAv↝, ERK↓, NF-kB↓, STAT3↓, COX2↓, Inflam↓, IronCh↑, lipid-P↓, ALAT↓, AST↓, TNF-α↓, *α-SMA↓, *SOD↑,

3290-

SIL,

A review of therapeutic potentials of milk thistle (Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents

Analysis,

Var,

hepatoP↑, chemoP↑, *lipid-P↓, *antiOx↑, tumCV↓, TumCMig↓, Apoptosis↑, ROS↑, GSH↓, Bcl-2↓, survivin↓, cycD1/CCND1↓, NOTCH1↓, BAX↑, NF-kB↓, COX2↓, LOX1↓, iNOS↓, TNF-α↓, IL1↓, Inflam↓, *toxicity↓, CXCR4↓, EGFR↓, ERK↓, MMP↓, Cyt‑c↑, TumCCA↑, RB1↑, P53↑, P21↑, p27↑, cycE/CCNE↓, CDK4↓, p‑pRB↓, Hif1a↓, cMyc↓, IL1β↓, IFN-γ↓, PCNA↓, PSA↓, CYP1A1↓,

3314-

SIL,

Silymarin: Unveiling its pharmacological spectrum and therapeutic potential in liver diseases—A comprehensive narrative review

Review,

NA,

*antiOx↑, *hepatoP↑, *Half-Life↑, *ROS↓, *GSH↑, *hepatoP↑, *lipid-P↓, *TNF-α↓, *IFN-γ↓, *IL2↓, *IL4↓, *NF-kB↓, *iNOS↓, *OATPs↓, *OCT4↓, *Inflam↓, *PGE2↓, MMPs↓, VEGF↓, angioG↓, STAT3↓, *ALAT↓, *AST↓, Dose↝,

3313-

SIL,

Silymarin attenuates post-weaning bisphenol A-induced renal injury by suppressing ferroptosis and amyloidosis through Kim-1/Nrf2/HO-1 signaling modulation in male Wistar rats

in-vivo,

NA,

50-100 mg/kg/day

Twenty-four male Wistar rats

*NRF2↑, *HO-1↑, *creat↓, *BUN↓, *RenoP↑, *MDA↓, *TNF-α↓, *IL1β↓, *Cyt‑c↓, *Casp3↓, *GSTs↓, *GSH↑, *GPx4↑, *SOD↑, *GSR↓, *Ferroptosis↓,

3307-

SIL,

Flavolignans from Silymarin as Nrf2 Bioactivators and Their Therapeutic Applications

Review,

Var,

*NRF2↑, *antiOx↑, *chemoP↑, *Inflam↓, *BioAv↑, eff↑, *NQO1↑, TNF-α↓, IL6↓, *GSH↑, *ROS↓, *MDA↓, eff↑, *hepatoP↑, *GPx↑, *SOD↑, *Catalase↑, *HO-1↑, *neuroP↑,

3300-

SIL,

Toward the definition of the mechanism of action of silymarin: activities related to cellular protection from toxic damage induced by chemotherapy

Review,

Var,

*ROS↓, *SOD↑, *hepatoP↑, *AST↓, *ALAT↓, *lipid-P↓, *GSH↑, *Catalase↑, *GSTs↑, *GSR↑, *TNF-α↓, *IFN-γ↓, *IL4↓, *IL2↓, *NF-kB↓, *IL10↑, *Inflam↓, COX2↓, Apoptosis↑, ChemoSen↑, PGE2↓, VEGF↓,

Showing Research Papers: 1 to 15 of 15

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

chemoP↑, 2, hepatoP↑, 1, neuroP↑, 1,
Total Targets: 65

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 6, Catalase↑, 5, Ferroptosis↓, 1, GPx↑, 2, GPx4↑, 1, GSH↑, 10, GSR↓, 1, GSR↑, 1, GSTs↓, 1, GSTs↑, 1, HO-1↑, 5, lipid-P↓, 7, MDA↓, 4, NQO1↑, 1, NRF2↑, 5, ROS↓, 8, SOD↑, 8, Trx↑, 1,

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 4, AMPK↑, 1, AMPK↝, 1, BUN↓, 1, PPARγ↑, 1, SIRT1↑, 1,

Cell Death ⓘ

Akt↑, 1, Akt↝, 1, Apoptosis↓, 1, BAX↑, 1, Bcl-2↑, 1, Casp3↓, 1, Cyt‑c↓, 1, Ferroptosis↓, 1, iNOS↓, 3, JNK↓, 1, p‑JNK↓, 1, MAPK↓, 2, MAPK↝, 1, necrosis↓, 2, p‑p38↓, 1,

Protein Folding & ER Stress ⓘ

HSP27↑, 1, HSPs↓, 1,

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 1, mTOR↑, 1, mTOR↝, 1, OCT4↓, 1, PI3K↝, 1,

Migration ⓘ

α-SMA↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 2,

Barriers & Transport ⓘ

BBB?, 1, BBB↑, 1, GLUT4↑, 1, OATPs↓, 1, P-gp↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 2, IFN-γ↓, 4, IL1↓, 1, IL10↓, 1, IL10↑, 2, IL1β↓, 3, IL2↓, 2, IL4↓, 4, IL6↓, 2, IL6↑, 1, Inflam↓, 7, NF-kB↓, 7, PGE2↓, 1, TLR4↓, 2, TNF-α↓, 13, TNF-β↓, 1,

Synaptic & Neurotransmission ⓘ

5HT↑, 1, AChE↓, 2, BChE↓, 1, BDNF↑, 4, tau↓, 1,

Protein Aggregation ⓘ

Aβ↓, 2, β-Amyloid↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↑, 2, BioAv↝, 2, Half-Life↓, 1, Half-Life↑, 1,

Clinical Biomarkers ⓘ

ALAT↓, 4, AST↓, 3, creat↓, 1, GutMicro↑, 1, IL6↓, 2, IL6↑, 1,

Functional Outcomes ⓘ

chemoP↑, 1, cognitive↑, 3, hepatoP↑, 9, memory↑, 3, Mood↑, 1, neuroP↑, 5, RenoP↑, 2, Strength↑, 1, toxicity↓, 1,
Total Targets: 96

Scientific Paper Hit Count for: TNF-α, TNF-α

15 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#:309  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

Silymarin (Milk Thistle) silibinin / TNF-α Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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