Database Query Results : Silymarin (Milk Thistle) silibinin, , α-SMA

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)
α-SMA, α-smooth muscle actin: Click to Expand ⟱
Source:
Type: protein
α-smooth muscle actin (α-SMA) is a protein that is often associated with cancer progression. It is a key component of the actin cytoskeleton and plays a crucial role in cell migration, invasion, and contraction.
α-SMA is often expressed by cancer-associated fibroblasts (CAFs), which are a type of stromal cell that surrounds the tumor. CAFs expressing α-SMA can promote tumor growth and metastasis.
High levels of α-SMA expression have been correlated with poor prognosis in various types of cancer, including breast, lung, and colorectal cancer.
Scientific Papers found: Click to Expand⟱
3323- SIL,    Anticancer therapeutic potential of silibinin: current trends, scope and relevance
- Review, Var, NA
Inflam↓, Silibinin has been shown to have anti-inflammatory, anti-angiogenic, antioxidant, and anti-metastatic properties
angioG↓,
antiOx↑,
TumMeta↓,
TumCP↓, silibinin helps in preventing proliferation of the tumor cells, initiating the cell cycle arrest, and induce cancer cells to die
TumCCA↑,
TumCD↑,
α-SMA↓, figure
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↓,

3294- SIL,    Silymarin: a review on paving the way towards promising pharmacological agent
- Review, Nor, NA - Review, Arthritis, NA
*hepatoP↑, It improves hepatic function, lessens hepatotoxicity caused by high acetaminophen intake, and can lessen oxidative stress in experimental mice, according to a study on animals
*Inflam↓,
*chemoP↑, moreover reducing the side effect of chemotherapeutic agents.
*glucose↓, Silymarin is effective anti-diabetic as it lowers serum glucose levels thus preventing the development of diabetic nephropathy
*antiOx↑, Various studies revealed that Silymarin could exert antioxidant properties in several mechanisms, which includes direct hindrance in free radical production,
*ROS↓,
*ACC↓, down-regulation of acetyl-CoA carboxylase, fatty acid synthase, and peroxisome proliferator-activated receptor
*FASN↓,
*radioP↑, More studies have revealed radioprotective properties of Silymarin in the testis tissues of mice and rats
*NF-kB↓, Silymarin inhibits NF-kB, down-regulates TGF-ß1 mRNA
*TGF-β↓,
*AST↓, Silymarin significantly decreased the elevation of aspartate aminotransferase (AST), alanine aminotransferase, and alkaline phosphatase in serum, and also reversed the altered expressions of α-smooth muscle actin in fibrotic tissue
*α-SMA↝,
*eff↑, Okda et al.[Citation76] currently reported that silymarin with ginger has significantly decreased the severity and incidence of liver fibrosis.
*neuroP↑, Researchers demonstrated that silymarin inhibits microglia activation, and protects dopaminergic neurons from lipopolysaccharide (LPS)-induced neurotoxicity
eff↑, The Silymarin with a selenium dose of 570 mg/d, for 6 months caused no side effects and was effective in reducing prostate cancer growth
ROS↓, Silymarin shows anti-cancerous properties considered to be linked to oxidative stress inhibition, apoptosis induction, growth cycle arrest, and mitochondrial pathway inhibition

3295- SIL,    Hepatoprotective effect of silymarin
- Review, NA, NA
*hepatoP↑, The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol, acetaminophen, and carbon tetrachloride.
*ROS↓,
*GSH↑, Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver.
*BioAv↝, For example, the level of silymarin absorption is between 20% and 50%. low solubility in water, low bioavailability, and poor intestinal absorption reduce its efficacy
ERK↓, treatment of melanoma cells with silybin attenuated the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 and RSK2,
NF-kB↓, silybin resulted in the reduced activation of nuclear factor-kappa B (NF-κB), activator protein-1, and STAT3
STAT3↓,
COX2↓, cytoprotective effect in liver is also caused by the inhibition of the cyclooxygenase cycle
Inflam↓, These affects reduce inflammation
IronCh↑, chelating iron, and slowing calcium metabolism,
lipid-P↓, Silymarin also affects intracellular glutathione, which prevents lipoperoxidation of membranes
ALAT↓, led to significantly reduced levels of alanine aminotransferase (ALT) and aspartame aminotransferase (AST) (AST/ALT < 1)
AST↓,
TNF-α↓, It also reduced the level of TNF-α, which reduces inflammation.
*α-SMA↓, There was also a reduction in FR and reduced markers of fibrosis such as alpha smooth muscle actin, collagen α 1(I), and in the caspase cytotoxicity marker.
*SOD↑, The activity of the enzymes superoxide dismutase (SOD) and glutathione-S-transferase (GST) increased significantly.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

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

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   TumCD↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 1,   E2Fs↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   PI3K↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,  

Migration ⓘ

MMP2↓, 1,   Slug↓, 1,   Snail↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   Zeb1↓, 1,   α-SMA↓, 1,  

Angiogenesis & Vasculature ⓘ

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

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL6↓, 1,   Inflam↓, 2,   JAK2↓, 1,   NF-kB↓, 2,   PD-L1↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   p‑EGFR↓, 1,   IL6↓, 1,   PD-L1↓, 1,  
Total Targets: 40

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   GSH↑, 1,   ROS↓, 2,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↓, 1,   FASN↓, 1,   glucose↓, 1,  

Migration ⓘ

TGF-β↓, 1,   α-SMA↓, 1,   α-SMA↝, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

AST↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   hepatoP↑, 2,   neuroP↑, 1,   radioP↑, 1,  
Total Targets: 19

Scientific Paper Hit Count for: α-SMA, α-smooth muscle actin
3 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#:719  State#:%  Dir#:%
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