condition found tbRes List
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 bioA (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 on acheive 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. Given low bioavailability seems unlikely one could acheieve levels in vivo to raise ROS(except 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↓, 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↓, OXPHOS↓, GRP78↑, 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


ERK, ERK signaling: Click to Expand ⟱
Source:
Type:
MAPK3 (ERK1)
ERK proteins are kinases that activate other proteins by adding a phosphate group. An overactivation of these proteins causes the cell cycle to stop.
The extracellular signal-regulated kinase (ERK) signaling pathway is a crucial component of the mitogen-activated protein kinase (MAPK) signaling cascade, which plays a significant role in regulating various cellular processes, including proliferation, differentiation, and survival. high levels of phosphorylated ERK (p-ERK) in tumor samples may indicate active ERK signaling and could correlate with aggressive tumor behavior

EEk singaling is frequently activated and is often associated with aggressive tumor behavior, treatment resistance, and poor outcomes.
Scientific Papers found: Click to Expand⟱
3319- SIL,    Silymarin and neurodegenerative diseases: Therapeutic potential and basic molecular mechanisms
- Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*neuroP↑, Silymarin can be used as a neuroprotective therapy against AD, PD and CI
*ROS↓, Silymarin prohibit oxidative stress, pathologic protein aggregation.
*Inflam↓, Silymarin inhibit neuroinflammation, apoptosis, and estrogenic receptor modulation.
*Apoptosis↓,
*BBB?, Silymarin, as a polyphenolic complex, can cross the blood-brain barrier (BBB)
*tau↓, inhibitory action of Silibinin on tau protein phosphorylation in the hippocampus and cortical region of the brain could describe an important neuro-protective effect against AD progression
*NF-kB↓, inhibiting the NF-κB pathway leading to attenuating the activity of NF-κB (
*IL1β↓, inhibition of inflammatory responses such as IL-1β and TNF-α mRNA gene
*TNF-α↓,
*IL4↓, enhance the production of IL-4 in the hippocampal region
*MAPK↓, down-regulation of MAPK activation
*memory↑, Silibinin exhibited its beneficial effect on improvement of memory impairment in rats
*cognitive↑, Silymarin was able to alleviated the impairment in cognitive, learning and memory ability caused by Aβ aggravation through making a reduction in oxidative stress in the hippocampal region
*Aβ↓,
*ROS↓,
*lipid-P↓, eduction in lipid peroxidation, controlling the GSH levels and then cellular anti-oxidant status improvement,
*GSH↑,
*MDA↓, Silymarin could reduce MDA content and significantly increased the reduced activity level of antioxidant enzyme, including SOD, CAT and GSH in the brain tissue induced by aluminum
*SOD↑,
*Catalase↑,
*AChE↓, Silibinin/ Silymarin, as a strong suppressor of AChE and BChE activity, exerted a positive effect against AD symptoms via increasing the ACh level in the brain
*BChE↓,
*p‑ERK↓, Silibinin could inhibit increased level of phosphorylated ERK, JNK and p38 (p-ERK, p-JNK and p-p38, respectively
*p‑JNK↓,
*p‑p38↓,
*GutMicro↑, demonstrated in APP/PS1 transgenic mice model of AD which was associated with controlling of the gut microbiota by both Silymarin and Silibinin
*COX2↓, Inhibition of the NF-κB pathway/ expression, Inhibition of IL-1β, TNF-α, COX_2 and iNOS level/ expression
*iNOS↓,
*TLR4↓, suppress TLR4 pathways and then subsequently diminished elevated level of TNF-α and up-regulated percentage of NF-κB mRNA expression
*neuroP↑, neuro-protective mechanisms on cerebral ischemia (CI)
*Strength↑, Silymarin decreased the loss of grip strength in the experimental rats
*AMPK↑, In SH-SY5Y cells, Silibinin blocked OGD/re-oxygenation- induced neuronal degeneration via AMPK activation as well as suppression in both ROS production and MMP reduction and even reduced neuronal apoptosis and necrosis.
*MMP↑,
*necrosis↓,
*NRF2↑, Silymarin up-regulated Nrf-2/HO-1 signaling (Yuan et al., 2017
*HO-1↑,

3331- SIL,    The clinical anti-inflammatory effects and underlying mechanisms of silymarin
- Review, NA, NA
*Inflam↓, anti-inflammatory mechanisms of silymarin,
*NF-kB↓, inhibition of the NF-kB and NLRP3 signaling pathways and the suppression of COX-2 and inducible nitric oxide synthase (iNOS) expression
*NLRP3↓,
*COX2↓,
*iNOS↓,
*neuroP↑, silymarin offers neuroprotection by inhibiting the phosphorylation of ERK1/2, JNK, and p38 MAPK and reducing the expression of the epidermal growth factor receptor and glial fibrillary acidic protein
*p‑ERK↓,
*p38↓,
*MAPK↓,
*EGFR↓,
*ROS↓, By the way, silymarin was reported to curb the formation of oxygen radicals and lipid peroxides.
*lipid-P?,
*5LO↓, Its anti-inflammatory effects were shown by inhibiting 5-LOX activity and obstructing the lipid peroxidation pathway to prevent the generation of ROS involved in inflammatory responses.

978- SIL,    A comprehensive evaluation of the therapeutic potential of silibinin: a ray of hope in cancer treatment
- Review, NA, NA
PI3K↓,
Akt↓,
NF-kB↓,
Wnt/(β-catenin)↓,
MAPK↓,
TumCP↓,
TumCCA↑, G0/G1 cell cycle arrest
Apoptosis↑, In T24 and UM-UC-3 human bladder cancer cells, silibinin treatment at a concentration of 10 μM significantly inhibited proliferation, migration, invasion, and induced apoptosis.
p‑EGFR↓,
JAK2↓,
STAT5↓,
cycD1↓,
hTERT↓,
AP-1↓,
MMP9↓,
miR-21↓,
miR-155↓,
Casp9↑,
BID↑,
ERK↓, ERK1/2
Akt2↓,
DNMT1↓,
P53↑,
survivin↓,
Casp3↑,
ROS↑, cytotoxicity of silibinin in Hep-2 cells was associated with the accumulation of intracellular reactive oxygen species (ROS), which could be mitigated by the ROS scavenger NAC.

1276- SIL,    Silibinin inhibits TPA-induced cell migration and MMP-9 expression in thyroid and breast cancer cells
- in-vitro, BC, NA - in-vitro, Thyroid, NA
TumCMig↓,
MMP9↓,
p‑MEK↓,
p‑ERK↓,

3282- SIL,    Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions
- Review, NA, NA
hepatoP↑, This group of flavonoids has been extensively studied and they have been used as hepato-protective substances
AntiCan↑, however, silymarin compounds have clear anticancer effects
TumCMig↓, decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, i
Hif1a↓, In prostate cancer cells silibinin inhibited HIF-1α translation
selectivity↑, antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected
toxicity∅, long history of silymarin use in human diseases without toxicity after prolonged administration.
*antiOx↑, as an antioxidant, by scavenging prooxidant free radicals
*Inflam↓,
*NA↓, antiinflammatory effects similar to those of indomethacin,
TumCCA↑, MDA-MB 486 breast cancer cells, G1 arrest was found due to increased p21 and decreased CDKs activity
P21↑,
CDK4↓,
NF-kB↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
ERK↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
PSA↓, Treating prostate carcinoma cells with silymarin the levels of PSA were significantly decreased and cell growth was inhibited through decreased CDK activity and induction of Cip1/p21 and Kip1/p27. 1
TumCG↓,
p27↑,
COX2↓, such as anti-COX2 and anti-IL-1α activity, 140 antiangiogenic effects through inhibition of VEGF secretion, upregulation of Insulin like Growth Factor Binding Protein 3 (IGFBP3), 141 and inhibition of androgen receptors.
IL1↓,
VEGF↓,
IGFBP3↑,
AR↓,
STAT3↓, downregulation of the STAT3 pathway which was seen in many cell models.
Telomerase↓, silymarin has the ability to decrease telomerase activity in prostate cancer cells
Cyt‑c↑, mitochondrial cytochrome C release-caspase activation.
Casp↑,
eff↝, Malignant p53 negative cells show only minimal apoptosis when treated with silymarin. Therefore, one conclusion is that silymarin may be useful in tumors with conserved p53.
HDAC↓, inhibit histone deacetylase activity;
HATs↑, increase histone acetyltransferase activity
Zeb1↓, reduce expression of the transcription factor ZEB1
E-cadherin↑, increase expression of E-cadherin;
miR-203↑, increase expression of miR-203
NHE1↓, reduce activation of sodium hydrogen isoform 1 exchanger (NHE1)
MMP2↓, target β catenin and reduce the levels of MMP2 and MMP9
MMP9↓,
PGE2↓, reduce activation of prostaglandin E2
Vim↓, suppress vimentin expression
Wnt↓, inhibit Wnt signaling
angioG↓, Silymarin inhibits angiogenesis.
VEGF↓, VEGF downregulation
*TIMP1↓, Silymarin has the capacity to decrease TIMP1 expression166–168 in mice.
EMT↓, found that silibinin had no effect on EMT. However, the opposite was found in other malignant tissues160–162 where it showed inhibitory effects.
TGF-β↓, Silibinin reduces the expression of TGF β2 in different tumors such as triple negative breast, 174 prostate, and colorectal cancers.
CD44↓, Silibinin decreased CD44 expression and the activation of EGFR (epidermal growth factor receptor)
EGFR↓,
PDGF↓, silibinin had the ability to downregulate PDFG in fibroblasts, thus decreasing proliferation.
*IL8↓, Flavonoids, in general, reduce levels of IL-8. Curcumin, 200 apigenin, 201 and silybin showed the ability to decrease IL-8 levels
SREBP1↓, Silymarin inhibited STAT3 phosphorylation and decreased the expression of intranuclear sterol regulatory element binding protein 1 (SREBP1), decreasing lipid synthesis.
MMP↓, reduced membrane potential and ATP content
ATP↓,
uPA↓, silibinin decreased MMP2, MMP9, and urokinase plasminogen activator receptor level (uPAR) in neuroblastoma cells. uPAR is also a marker of cell invasion.
PD-L1↓, Silibinin inhibits PD-L1 by impeding STAT5 binding in NSCLC.
NOTCH↓, Silybin inhibited Notch signaling in hepatocellular carcinoma cells showing antitumoral effects
*SIRT1↑, Silymarin can also increase SIRT1 expression in other tissues, such as hippocampus, 221 articular chondrocytes, 222 and heart muscle
SIRT1↓, Silymarin seems to act differently in tumors: in lung cancer cells SIRT downregulated SIRT1 and exerted multiple antitumor effects such as reduced adhesion and migration and increased apoptosis.
CA↓, Silymarin has the ability to inhibit CA isoforms CA I and CA II.
Ca+2↑, ilymarin increases mitochondrial release of Ca++ and lowers mitochondrial membrane potential in cancer cell
chemoP↑, Silymarin: Decreasing Side Effects and Toxicity of Chemotherapeutic Drugs
cardioP↑, There is also evidence that it protects the heart from doxorubicin toxicity, however, it is less potent than quercetin in this effect.
Dose↝, oral administration of 240 mg of silybin to 6 healthy volunteers the following results were obtained 377 : maximum\,plasmaconcentration0.34±0.16⁢𝜇⁢g/m⁢L
Half-Life↝, and time to maximum plasma concentration 1.32 ± 0.45 h. Absorption half life 0.17 ± 0.09 h, elimination half life 6.32 ± 3.94 h
BioAv↓, silymarin is not soluble in water and oral administration shows poor absorption in the alimentary tract (approximately 1% in rats,
BioAv↓, Our conclusion is that, from a bioavailability standpoint, it is much easier to achieve migration inhibition, than proliferative reduction.
BioAv↓, Combination with succinate: is available on the market under the trade mark Legalon® (bis hemisuccinate silybin). Combination with phosphatidylcholine:
toxicity↝, 13 g daily per os divided into 3 doses was well tolerated. The most frequent adverse event was asymptomatic liver toxicity.
Half-Life↓, It may be necessary to administer 800 mg 4 times a day because the half-life is short.
ROS↓, its ability as an antioxidant reduces ROS production
FAK↓, Silibinin decreased human osteosarcoma cell invasion through Erk inhibition of a FAK/ERK/uPA/MMP2 pathway

3288- SIL,    Silymarin in cancer therapy: Mechanisms of action, protective roles in chemotherapy-induced toxicity, and nanoformulations
- Review, Var, NA
Inflam↓, Silymarin, a milk thistle extract, has anti-inflammatory, immunomodulatory, anti-lipid peroxidative, anti-fibrotic, anti-oxidative, and anti-proliferative properties.
lipid-P↓,
TumMeta↓, Silymarin exhibits not only anti-cancer functions through modulating various hallmarks of cancer, including cell cycle, metastasis, angiogenesis, apoptosis, and autophagy, by targeting a plethora of molecules
angioG↓,
chemoP↑, but also plays protective roles against chemotherapy-induced toxicity, such as nephrotoxicity,
EMT↓, Figure 2, Metastasis
HDAC↓,
HATs↑,
MMPs↓,
uPA↓,
PI3K↓,
Akt↓,
VEGF↓, Angiogenesis
CD31↓,
Hif1a↓,
VEGFR2↓,
Raf↓,
MEK↓,
ERK↓,
BIM↓, apoptosis
BAX↑,
Bcl-2↓,
Bcl-xL↓,
Casp↑,
MAPK↓,
P53↑,
LC3II↑, Autophagy
mTOR↓,
YAP/TEAD↓,
*BioAv↓, Additionally, the oral bioavailability of silymarin in rats is only 0.73 %
MMP↓, silymarin treatment reduced mitochondrial transmembrane potential, leading to an increase in cytosolic cytochrome c (Cyt c), downregulating proliferation-associated proteins (PCNA, c-Myc, cyclin D1, and β-catenin)
Cyt‑c↑,
PCNA↓,
cMyc↓,
cycD1↓,
β-catenin/ZEB1↓,
survivin↓, and anti-apoptotic proteins (survivin and Bcl-2), and upregulating pro-apoptotic proteins (caspase-3, Bax, APAF-1, and p53)
APAF1↑,
Casp3↑,
MDSCs↓, ↓MDSCs, ↓IL-10, ↑IL-2 and IFN-γ
IL10↓,
IL2↑,
IFN-γ↑,
hepatoP↑, Moreover, in a randomized clinical trial, silymarin attenuated hepatoxicity in non-metastatic breast cancer patients undergoing a doxorubicin/cyclophosphamide-paclitaxel regimen
cardioP↑, For example, Rašković et al. studied the hepatoprotective and cardioprotective effects of silymarin (60 mg/kg orally) in rats following DOX
GSH↑, silymarin could protect the kidney and heart from ADR toxicity by protecting against glutathione (GSH) depletion and inhibiting lipid peroxidation
neuroP↑, silymarin attenuated the neurotoxicity of docetaxel by reducing apoptosis, inflammation, and oxidative stress

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, NA
hepatoP↑, well as hepatoprotective agents.
chemoP↑, silymarin could be beneficial to oncology patients, especially for the treatment of the side effects of anticancer chemotherapeutics.
*lipid-P↓, Silymarin has been shown to significantly reduce lipid peroxidation and exhibit anti-oxidant, antihypertensive, antidiabetic, and hepatoprotective effects
*antiOx↑,
tumCV↓, reduces the viability, adhesion, and migration of tumor cells by induction of apoptosis and formation of reactive oxygen species (ROS), reducing glutathione levels, B-cell lymphoma 2 (Bcl-2), survivin, cyclin D1, Notch 1 intracellular domain (NICD),
TumCMig↓,
Apoptosis↑,
ROS↑,
GSH↓,
Bcl-2↓,
survivin↓,
cycD1↓,
NOTCH1↓,
BAX↑, as well as enhancing the amount of Bcl-2-associated X protein (Bax) level (
NF-kB↓, The suppression of NK-κB-regulated gene products (e.g., cyclooxygenase-2 (COX-2), lipoxygenase (LOX), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF), and interleukin-1 (IL-1)) mediates the anti-inflammatory effect of silymarin
COX2↓,
LOX1↓,
iNOS↓,
TNF-α↓,
IL1↓,
Inflam↓,
*toxicity↓, Silymarin is also safe for humans, hence at therapeutic doses patients demonstrated no negative effects at the high dose of 700 mg, three times a day, for 24 weeks
CXCR4↓, fig 2
EGFR↓,
ERK↓,
MMP↓, reduction in mitochondrial transmembrane potential due to an increase in cytosolic cytochrome complex (Cyt c) levels.
Cyt‑c↑,
TumCCA↑, Moreover, silymarin increased the percentage of cells in the gap 0/gap 1 (G0/G1) phase and decreased the percentage of cells in the synthesis (S)-phase,
RB1↑, concomitant up-regulation of retinoblastoma protein (Rb), p53, cyclin-dependent kinase inhibitor 1 (p21Cip1), and cyclin-dependent kinase inhibitor 1B (p27Kip1)
P53↑,
P21↑,
p27↑,
cycE↓, and down-regulation of cyclin D1, cyclin E, cyclin-dependent kinase 4 (CDK4), and phospho-Rb
CDK4↓,
p‑pRB↓,
Hif1a↓, silibinin inhibited proliferation of Hep3B cells due to simultaneous induction of apoptosis and prevented the accumulation
cMyc↓, Silibinin also reduces cellular myelocytomatosis oncogene (c-MYC) expression, a key regulator of cancer metabolism in pancreatic cancer cells
IL1β↓, Silymarin can also inhibit the production of inflammatory cytokines, such as interleukin-1beta (IL-1β), interferon-gamma (IFNγ),
IFN-γ↓,
PCNA↓, ilymarin suppresses the high proliferative activity of cells started with a carcinogen so that it significantly inhibits proliferating cell nuclear antigen (PCNA) and cyclin D1 labeling indices
PSA↓, In another patent, S. marianum has been used as an estrogen receptor β-agonist and an inhibitor of PSA for treating prostate cancer
CYP1A1↓, Silymarin prevents the expression of CYP1A1 and COX-2

3293- SIL,    Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer
- Review, Var, NA
hepatoP↑, Silymarin has been shown to protect the liver in both experimental models and clinical studies.
TumMeta↓, In addition to its anti-metastatic activity, silymarin has also been reported to exhibit anti-inflammatory activity
Inflam↓,
chemoP↑, The chemoprotective effects of silymarin and silibinin (its major constituent) suggest they could be applied to reduce the side effects and increase the anti-cancer effects of chemotherapy and radiotherapy in various cancer types, especially in GC
radioP↑,
Half-Life↝, silibinin showed a 6-h half-life
*GSTs↑, Oral administration of silibinin leads to an increase in glutathione S-transferase (GST) and quinone reductase (QR) activity in the liver, stomach, lungs, small bowel, and skin, in a time- and dose-dependent manner
p‑JNK↑, Silymarin significantly up-regulated the levels of phosphorylated (p)-JNK, Bax, and p-p38, and cleaved poly-ADP ribose polymerase (PARP), while it down-regulated Bcl-2 and p-ERK1/2 expression, in a dose-dependent manner.
BAX↑,
p‑p38↑,
cl‑PARP↑,
Bcl-2↓,
p‑ERK↓,
TumVol↓, Silymarin (100 mg/kg) decreased the tumor volume in an AGS xenograft mouse model and increased apoptosis in the tumors.
eff↑, resveratrol, lycopene, sulforaphane, or silybinin have been shown to have anti-tumor activity, along with relatively low-toxicity to normal cells. Therefore they could be used in combination
TumCCA↑, Silibinin induced apoptosis and cell cycle arrest in G2/M phase in MGC803 cells
STAT3↓, Silybinin down-regulated p-STAT3 protein expression and also its downstream genes (such as Mcl-1, survivin, Bcl-xL, and STAT3).
Mcl-1↓,
survivin↓,
Bcl-xL↓,
Casp3↑, Silibinin increased caspase-3 and caspase-9 mRNA and protein expression levels.
Casp9↑,
eff↑, Therefore, the anti-cancer activity of silibinin might be enhanced by HDAC inhibitors
CXCR4↓, Silymarin significantly induced apoptosis and decreased the expression level of CXCR-4 in HepG2 cells in a concentration-dependent manner.
Dose↝, It has been shown to be tolerated by patients at a large dose (700 mg) thrice per day over six months

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.

3301- SIL,    Critical review of therapeutic potential of silymarin in cancer: A bioactive polyphenolic flavonoid
- Review, Var, NA
Inflam↓, graphical abstract
TumCCA↑,
Apoptosis↓,
TumMeta↓,
TumCG↓,
angioG↓,
chemoP↑, The chemo-protective effects of silymarin and silibinin propose that they could be applied to decrease the side effects and increase the anti-tumor effects of chemotherapy and radiotherapy in different types of cancers.
radioP↑,
p‑ERK↓, fig 2
p‑p38↓,
p‑JNK↓,
P53↑,
Bcl-2↓,
Bcl-xL↓,
TGF-β↓,
MMP2↓,
MMP9↓,
E-cadherin↑,
Wnt↓,
Vim↓,
VEGF↓,
IL6↓,
STAT3↓,
*ROS↓,
IL1β↓,
PGE2↓,
CDK1↓, Causes cell cycle arrest by down-regulating CDK1, cyclinB1, survivin, Bcl-xl, Mcl-1 and activating caspase 3 and caspase 9,
CycB↓,
survivin↓,
Mcl-1↓,
Casp3↑,
Casp9↑,
cMyc↓, Silibinin treatment diminishes c-MYC
COX2↓, Silibinin considerably down-regulated the expression of COX-2, HIF-1α, VEGF, Ang-2, Ang-4, MMP-2, MMP-9, CCR-2 and CXCR-4
Hif1a↓,
CXCR4↓,
CSCs↓, HCT-116 cells, Induction of apoptosis, suppression of migration, elimination of CSCs. Attenuation of EMT via decreased expression of N- cadherin and vimentin and increased expression of (E-cadherin).
EMT↓,
N-cadherin↓,
PCNA↓, Decrease in PCNA and cyclin D1 level.
cycD1↓,
ROS↑, Hepatocellular carcinoma: Silymarin nanoemulsion reduced the cell viability and increased ROS intensity and chromatin condensation.
eff↑, Silymarin + Curcumin
eff↑, Silibinin + Metformin
eff↑, Silibinin + 1, 25-vitamin D3
HER2/EBBR2↓, Significant down regulation of HER2 by 150 and 250 µM of silybin after 24, 48 and 72 h.

3304- SIL,    Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells
- in-vitro, GC, AGS - in-vivo, NA, NA
BAX↑, Silymarin increased the expression of Bax, phosphorylated (p)-JNK and p-p38, and cleaved poly-ADP ribose polymerase, and decreased the levels of Bcl-2 and p-ERK1/2 in a concentration-dependent manner.
p‑JNK↑,
p‑p38↑,
cl‑PARP↑,
Bcl-2↓,
p‑ERK↓,
TumVol↓, Silymarin (100 mg/kg) significantly decreased the AGS tumor volume and increased apoptosis
Apoptosis↑,
tumCV↓,

3305- SIL,    Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vivo, NA, NA
TumCP↓, Silymarin decreased the viability and proliferation of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner.
tumCV↓,
BAX↑, Silymarin increased the levels of Bax, cleaved poly-ADP ribose polymerase, cleaved caspase-9 and phosphorylated (p-)JNK, and decreased the levels of Bcl-2, p-P38 and p-ERK1/2.
cl‑PARP↑,
Casp9↑,
p‑JNK↑,
Bcl-2↓,
p‑p38↓,
p‑ERK↓,
*toxicity∅, In mice treated with silymarin for 3 weeks (25 and 50 mg/kg), MCF-7 tumor growth was inhibited without organ toxicity
Dose↝, cell viability increased to 110% @ low dose 25ug/ml before dropping see figure 1
*hepatoP↑, silymarin is used as a healthy functional food in recognition of the hepatoprotective effects and has been reported the various effects such as inflammation (750 mg/kg/day), antioxidants (150 mg/kg−1) and anti-cancer
Inflam↓,
AntiCan↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   Akt2↓,1,   ALAT↓,1,   angioG↓,3,   AntiCan↑,2,   AP-1↓,1,   APAF1↑,1,   Apoptosis↓,1,   Apoptosis↑,3,   AR↓,1,   AST↓,1,   ATP↓,1,   BAX↑,5,   Bcl-2↓,6,   Bcl-xL↓,3,   BID↑,1,   BIM↓,1,   BioAv↓,3,   CA↓,1,   Ca+2↑,1,   cardioP↑,2,   Casp↑,2,   Casp3↑,4,   Casp9↑,4,   CD31↓,1,   CD44↓,1,   CDK1↓,1,   CDK4↓,2,   chemoP↑,5,   cMyc↓,3,   COX2↓,4,   CSCs↓,1,   CXCR4↓,3,   CycB↓,1,   cycD1↓,4,   cycE↓,1,   CYP1A1↓,1,   Cyt‑c↑,3,   DNMT1↓,1,   Dose↝,3,   E-cadherin↑,2,   eff↑,5,   eff↝,1,   EGFR↓,2,   p‑EGFR↓,1,   EMT↓,3,   ERK↓,5,   p‑ERK↓,5,   FAK↓,1,   GSH↓,1,   GSH↑,1,   Half-Life↓,1,   Half-Life↝,2,   HATs↑,2,   HDAC↓,2,   hepatoP↑,4,   HER2/EBBR2↓,1,   Hif1a↓,4,   hTERT↓,1,   IFN-γ↓,1,   IFN-γ↑,1,   IGFBP3↑,1,   IL1↓,2,   IL10↓,1,   IL1β↓,2,   IL2↑,1,   IL6↓,1,   Inflam↓,6,   iNOS↓,1,   IronCh↑,1,   JAK2↓,1,   p‑JNK↓,1,   p‑JNK↑,3,   LC3II↑,1,   lipid-P↓,2,   LOX1↓,1,   MAPK↓,2,   Mcl-1↓,2,   MDSCs↓,1,   MEK↓,1,   p‑MEK↓,1,   miR-155↓,1,   miR-203↑,1,   miR-21↓,1,   MMP↓,3,   MMP2↓,2,   MMP9↓,4,   MMPs↓,1,   mTOR↓,1,   N-cadherin↓,1,   neuroP↑,1,   NF-kB↓,4,   NHE1↓,1,   NOTCH↓,1,   NOTCH1↓,1,   P21↑,2,   p27↑,2,   p‑p38↓,2,   p‑p38↑,2,   P53↑,4,   cl‑PARP↑,3,   PCNA↓,3,   PD-L1↓,1,   PDGF↓,1,   PGE2↓,2,   PI3K↓,2,   p‑pRB↓,1,   PSA↓,2,   radioP↑,2,   Raf↓,1,   RB1↑,1,   ROS↓,1,   ROS↑,3,   selectivity↑,1,   SIRT1↓,1,   SREBP1↓,1,   STAT3↓,4,   STAT5↓,1,   survivin↓,5,   Telomerase↓,1,   TGF-β↓,2,   TNF-α↓,2,   toxicity↝,1,   toxicity∅,1,   TumCCA↑,5,   TumCG↓,2,   TumCMig↓,3,   TumCP↓,2,   tumCV↓,3,   TumMeta↓,3,   TumVol↓,2,   uPA↓,2,   VEGF↓,4,   VEGFR2↓,1,   Vim↓,2,   Wnt↓,2,   Wnt/(β-catenin)↓,1,   YAP/TEAD↓,1,   Zeb1↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 140

Results for Effect on Normal Cells:
5LO↓,1,   AChE↓,1,   AMPK↑,1,   antiOx↑,2,   Apoptosis↓,1,   Aβ↓,1,   BBB?,1,   BChE↓,1,   BioAv↓,1,   BioAv↝,1,   Catalase↑,1,   cognitive↑,1,   COX2↓,2,   EGFR↓,1,   p‑ERK↓,2,   GSH↑,2,   GSTs↑,1,   GutMicro↑,1,   hepatoP↑,2,   HO-1↑,1,   IL1β↓,1,   IL4↓,1,   IL8↓,1,   Inflam↓,3,   iNOS↓,2,   p‑JNK↓,1,   lipid-P?,1,   lipid-P↓,2,   MAPK↓,2,   MDA↓,1,   memory↑,1,   MMP↑,1,   NA↓,1,   necrosis↓,1,   neuroP↑,3,   NF-kB↓,2,   NLRP3↓,1,   NRF2↑,1,   p38↓,1,   p‑p38↓,1,   ROS↓,5,   SIRT1↑,1,   SOD↑,2,   Strength↑,1,   tau↓,1,   TIMP1↓,1,   TLR4↓,1,   TNF-α↓,1,   toxicity↓,1,   toxicity∅,1,   α-SMA↓,1,  
Total Targets: 51

Scientific Paper Hit Count for: ERK, ERK signaling
12 Silymarin (Milk Thistle) silibinin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:154  Target#:105  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page