Silymarin (Milk Thistle) silibinin / neuroP 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↓, 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)
neuroP, neuroprotective: Click to Expand ⟱
Source:
Type:
Neuroprotective refers to the ability of a substance, intervention, or strategy to preserve the structure and function of nerve cells (neurons) against injury or degeneration.
-While cancer and neurodegenerative processes might seem distinct, there is significant overlap in terms of treatment-related neurotoxicity, shared molecular mechanisms, and the potential for therapies that provide neuroprotection during cancer treatment.
Scientific Papers found: Click to Expand⟱
3324- SIL,    Silymarin prevents NLRP3 inflammasome activation and protects against intracerebral hemorrhage
*ROS↓, *TAC↑, *NF-kB↓, *IL2↓, *NRF2↑, *HO-1↑, *neuroP↑, *Inflam↓, *NLRP3↓,
3331- SIL,    The clinical anti-inflammatory effects and underlying mechanisms of silymarin
- Review, NA, NA
*Inflam↓, *NF-kB↓, *NLRP3↓, *COX2↓, *iNOS↓, *neuroP↑, *p‑ERK↓, *p38↓, *MAPK↓, *EGFR↓, *ROS↓, *lipid-P?, *5LO↓,
3330- SIL,    Mechanistic Insights into the Pharmacological Significance of Silymarin
- Review, Var, NA
*neuroP↑, *hepatoP↑, *cardioP↑, *antiOx↓, *NLRP3↓, *NAD↑, ROS↓, NLRP3↓, TumCMig↓, *COX2↓, *iNOS↓, *MPO↓, *AChE↓, *LDH↓, *Telomerase↓, *Fas↓,
3320- SIL,    Neuroprotective Potential of Silymarin against CNS Disorders: Insight into the Pathways and Molecular Mechanisms of Action
- Review, AD, NA
*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, NA - Review, Park, NA - Review, Stroke, NA
*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, 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↑,
3317- SIL,    Unlocking the Neuroprotective Potential of Silymarin: A Promising Ally in Safeguarding the Brain from Alzheimer's Disease and Other Neurological Disorders
- Review, NA, NA
*neuroP↑,
3316- SIL,  Chemo,    Silymarin Nanoparticles Counteract Cognitive Impairment Induced by Doxorubicin and Cyclophosphamide in Rats; Insights into Mitochondrial Dysfunction and Nrf2/HO-1 Axis
Inflam↓, antiOx↓, neuroP↑, cognitive↑, NRF2↑, HO-1↑, memory↑, AChE↓, Casp3↓,
3653- SIL,    Silibinin ameliorates Aβ25-35-induced memory deficits in rats by modulating autophagy and attenuating neuroinflammation as well as oxidative stress
- in-vivo, AD, NA
*hepatoP↑, *neuroP↑, *cognitive↑, *memory↑, *Inflam↓, *GSH↑, *MDA↓, *Inflam↓, *antiOx↓,
3655- SIL,    Protective effect of silymarin on oxidative stress in rat brain
- in-vivo, AD, NA
*GSH↑, *VitC↑, *SOD↑, *lipid-P↓, *ROS↓, *hepatoP↑, *neuroP↑,
3654- SIL,    Effect of silymarin on biochemical parameters of oxidative stress in aged and young rat brain
- in-vivo, AD, NA
*ROS↓, *neuroP↑, *GSH↑, *SOD↑,
3315- SIL,    Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats
- in-vivo, Nor, NA
neuroP↑, *NRF2↑, *HO-1↑, *lipid-P↓, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, *NF-kB↓, *TNF-α↓, *JNK↓, *Bcl-2↑, *BAX↑,
3288- SIL,    Silymarin in cancer therapy: Mechanisms of action, protective roles in chemotherapy-induced toxicity, and nanoformulations
- Review, Var, NA
Inflam↓, lipid-P↓, TumMeta↓, angioG↓, chemoP↑, EMT↓, HDAC↓, HATs↑, MMPs↓, uPA↓, PI3K↓, Akt↓, VEGF↓, CD31↓, Hif1a↓, VEGFR2↓, Raf↓, MEK↓, ERK↓, BIM↓, BAX↑, Bcl-2↓, Bcl-xL↓, Casp↑, MAPK↓, P53↑, LC3II↑, mTOR↓, YAP/TEAD↓, *BioAv↓, MMP↓, Cyt‑c↑, PCNA↓, cMyc↓, cycD1/CCND1↓, β-catenin/ZEB1↓, survivin↓, APAF1↑, Casp3↑, MDSCs↓, IL10↓, IL2↑, IFN-γ↑, hepatoP↑, cardioP↑, GSH↑, neuroP↑,
3294- SIL,    Silymarin: a review on paving the way towards promising pharmacological agent
- Review, Nor, NA - Review, Arthritis, NA
*hepatoP↑, *Inflam↓, *chemoP↑, *glucose↓, *antiOx↑, *ROS↓, *ACC↓, *FASN↓, *radioP↑, *NF-kB↓, *TGF-β↓, *AST↓, *α-SMA↝, *eff↑, *neuroP↑, eff↑, ROS↓,
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↑,

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:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   GSH↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 2,  

Mitochondria & Bioenergetics ⓘ

MEK↓, 1,   MMP↓, 1,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,  

Cell Death ⓘ

Akt↓, 1,   APAF1↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   BIM↓, 1,   Casp↑, 1,   Casp3↓, 1,   Casp3↑, 1,   Cyt‑c↑, 1,   MAPK↓, 1,   survivin↓, 1,   YAP/TEAD↓, 1,  

Transcription & Epigenetics ⓘ

HATs↑, 1,  

Autophagy & Lysosomes ⓘ

LC3II↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,   HDAC↓, 1,   mTOR↓, 1,   PI3K↓, 1,  

Migration ⓘ

CD31↓, 1,   MMPs↓, 1,   TumCMig↓, 1,   TumMeta↓, 1,   uPA↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

IFN-γ↑, 1,   IL10↓, 1,   IL2↑, 1,   IL6↓, 1,   Inflam↓, 2,   MDSCs↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 3,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   chemoP↑, 1,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 3,  
Total Targets: 60

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 2,   antiOx↑, 2,   Catalase↑, 4,   GPx↑, 2,   GSH↑, 7,   HO-1↑, 5,   lipid-P?, 1,   lipid-P↓, 3,   MDA↓, 4,   MPO↓, 1,   NQO1↑, 1,   NRF2↑, 5,   ROS↓, 10,   SOD↑, 6,   TAC↑, 1,   VitC↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↓, 1,   AMPK↑, 1,   FASN↓, 1,   glucose↓, 1,   LDH↓, 1,   NAD↑, 1,  

Cell Death ⓘ

Akt↑, 1,   Apoptosis↓, 1,   BAX↑, 1,   Bcl-2↑, 1,   Fas↓, 1,   iNOS↓, 4,   JNK↓, 1,   p‑JNK↓, 1,   MAPK↓, 3,   necrosis↓, 1,   p38↓, 1,   p‑p38↓, 1,   Telomerase↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 2,   mTOR↑, 1,  

Migration ⓘ

5LO↓, 1,   TGF-β↓, 1,   α-SMA↝, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   NO↓, 2,  

Barriers & Transport ⓘ

BBB?, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   IL10↑, 1,   IL1β↓, 2,   IL2↓, 1,   IL4↓, 1,   IL6↑, 1,   Inflam↓, 8,   NF-kB↓, 7,   TLR4↓, 2,   TNF-α↓, 4,   TNF-β↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 3,   BChE↓, 1,   BDNF↑, 1,   tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,   NLRP3↓, 3,   β-Amyloid↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

AST↓, 1,   EGFR↓, 1,   GutMicro↑, 1,   IL6↑, 1,   LDH↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   chemoP↑, 2,   cognitive↑, 3,   hepatoP↑, 7,   memory↑, 3,   neuroP↑, 13,   radioP↑, 1,   Strength↑, 1,  
Total Targets: 78

Scientific Paper Hit Count for: neuroP, neuroprotective
15 Silymarin (Milk Thistle) silibinin
1 Chemotherapy
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#:1105  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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