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


Hif1a, HIF1α/HIF1a: Click to Expand ⟱
Source:
Type:
Hypoxia-Inducible-Factor 1A (HIF1A gene, HIF1α, HIF-1α protein product)
-Dominantly expressed under hypoxia(low oxygen levels) in solid tumor cells
-HIF1A induces the expression of vascular endothelial growth factor (VEGF)
-High HIF-1α expression is associated with Poor prognosis
-Low HIF-1α expression is associated with Better prognosis

-Functionally, HIF-1α is reported to regulate glycolysis, whilst HIF-2α regulates genes associated with lipoprotein metabolism.
-Cancer cells produce HIF in response to hypoxia in order to generate more VEGF that promote angiogenesis

Key mediators of aerobic glycolysis regulated by HIF-1α.
-GLUT-1 → regulation of the flux of glucose into cells.
-HK2 → catalysis of the first step of glucose metabolism.
-PKM2 → regulation of rate-limiting step of glycolysis.
-Phosphorylation of PDH complex by PDK → blockage of OXPHOS and promotion of aerobic glycolysis.
-LDH (LDHA): Rapid ATP production, conversion of pyruvate to lactate;

HIF-1α Inhibitors:
-Curcumin: disruption of signaling pathways that stabilize HIF-1α (ie downregulate).
-Resveratrol: downregulate HIF-1α protein accumulation under hypoxic conditions.
-EGCG: modulation of upstream signaling pathways, leading to decreased HIF-1α activity.
-Emodin: reduce HIF-1α expression. (under hypoxia).
-Apigenin: inhibit HIF-1α accumulation.
Scientific Papers found: Click to Expand⟱
3325- SIL,    Modulatory effect of silymarin on pulmonary vascular dysfunction through HIF-1α-iNOS following rat lung ischemia-reperfusion injury
- in-vivo, Nor, NA
*Inflam↓, Following silymarin treatment, inflammation and oxidative stress in the lung I/R-injury rats were demonstrably suppressed.
*ROS↓,
*Casp3↑, Treatment with silymarin also inhibited the activation of caspase-3 and −9, and hypoxia inducible factor-1α (HIF-1α) and inducible nitric oxide synthase (iNOS) protein expression in the lung I/R-injury rats.
*Casp9↑,
*Hif1a↓,
*iNOS↓,
*SOD↑, Silymarin increases SOD and reduces MDA levels in rat lungs following I/R injury
*MDA↓,

3326- SIL,    Silymarin suppresses proliferation of human hepatocellular carcinoma cells under hypoxia through downregulation of the HIF-1α/VEGF pathway
- in-vitro, Liver, HepG2 - in-vitro, Liver, Hep3B
*hepatoP↑, Silymarin (SM) had been used as a traditional liver protective drug for decades
chemoP↑, SM has chemopreventive and chemosensitizing effects on multiple cancers.
ChemoSen↑,
TumCP↓, SM reduced cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in HepG2 and Hep3B cells under hypoxia conditions.
TumCMig↓,
TumCI↓,
Hif1a↓, The inhibitory effect of SM on HepG2 and Hep3B cells under hypoxia is partially via downregulating HIF-1α/VEGF signaling
VEGF↓,
angioG↓,

3327- SIL,    Effects of silymarin on HIF‑1α and MDR1 expression in HepG‑2 cells under hypoxia
- in-vitro, Liver, HepG2
MDR1↓, while the MDR1 mRNA expression decreased in a concentration-dependent manner
Hif1a↓, Additionally, the HIF?1α and P?Gp protein expression levels of the 10, 20, and 40 mg/L SM treatment groups decreased in a concentration-dependent manner compared with the control group
P-gp↓,

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↓, SIL attenuated testosterone-induced nuclear factor-kappa B (NF-κB), cyclooxygenase-II (COX-II), and inducible nitric oxide synthase (iNOS) upregulation
*Hif1a↓, Testosterone-induced downregulation of phosphatase and tensin homolog (PTEN) and upregulation of hypoxia-inducible factor 1α (HIF-1α) were alleviated by SIL.
*PTEN↑,
*Weight↓, Concomitant administration of SIL (50 mg/kg) significantly decreased the prostate weight and prostate index induced by testosterone by 0.64-fold and 0.68-fold, respectively
*NO↓, co-treatment with SIL significantly ameliorated testosterone-induced rise in NO
*IL6↓, SIL-treated group significantly down- regulated mRNA expression of IL-6 and IL-8 compared to testosterone-treated group
*IL8↓,
*COX2↓, SIL suppressed NF-κB, COX-II, and iNOS expressions as well as nitric oxide level in several experimental models
*iNOS↓,

3329- SIL,    Silymarin regulates the HIF-1 and iNOS expression in the brain and Gills of the hypoxic-reoxygenated rainbow trout (Oncorhynchus mykis)
- in-vivo, Nor, NA
*NO↓, SMN lowered the H/R-elevated NO, MDA and carbonylated protein levels, while it enhanced the TAC level.
*MDA↓,
*TAC↑,
*Hif1a↓, SMN regulated the H/R up-regulated level of HIF-1α and iNOS in examined tissues.
*iNOS↓,

1001- SIL,    Silibinin down-regulates PD-L1 expression in nasopharyngeal carcinoma by interfering with tumor cell glycolytic metabolism
- in-vitro, NA, NA
TumCG↓,
Glycolysis↓, Silibinin potently inhibits tumor growth and promotes a shift from aerobic glycolysis toward oxidative phosphorylation.
OXPHOS↑,
LDHA↓,
lactateProd↓,
i-citrate↑,
Hif1a↓,
PD-L1↓, silibinin can alter PD-L1 expression by interfering with HIF-1α/LDH-A

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

3289- SIL,    Silymarin: a promising modulator of apoptosis and survival signaling in cancer
- Review, Var, NA
*BioAv↝, silymarin’s poor bioavailability and limited thérapeutic efficacy have been overcome by encapsulation of silymarin into nanoparticles
*BioAv↓, Silymarin is barely 20–50% absorbed by the GIT cells and has an absolute oral bioavailability of 0.95%
Fas↑, silibinin, enhances the Fas pathway in most cancers cells by upregulating the Fas and Fas L
FasL↑,
FADD↑, silymarin triggered apoptosis via upregulating the expression of FADD (Fig. 2b), a downstream component of the death receptor pathway, subsequently leading to the cleavage of procaspase 8 and initiation of apoptotic cell death
pro‑Casp8↑,
Apoptosis↑,
DR5↑, silymarin promotes apoptosis through the death receptor-mediated pathway, contributing to its anticancer effects
Bcl-2↑, Bcl-2, an anti-apoptotic protein, was decreased
BAX↑, Bax is also upregulated and leads to the activation of caspase-3.
Casp3↑,
PI3K↓, Silibinin inhibits the PI3K activity, leading to the reduction of FoxM1 (Forkhead box M1) and the subsequent activation of the mitochondrial apoptotic pathway
Foxm1↓,
p‑mTOR↓, inhibiting phosphorylation of several key components in this pathway, such as mTOR, p70S6K and 4E-BP1
p‑P70S6K↓,
Hif1a↓, mTOR pathway signaling in turn may result in low levels of HIF-1α due to the unfavorable conditions of hypoxia.
Akt↑, silibinin activates the Akt pathway in cervical cancer cells. This activation of Akt could have some bearing on the overall antitumor activity of silibinin in cervical cancer cells.
angioG↓, silibinin inhibited STAT3, HIF-1α, and NF-κB, thereby reducing the population of lung macrophages and limiting angiogenesis
STAT3↓,
NF-kB↓,
lipid-P↓, silibinin delays the progression of endometrial carcinoma via inhibiting STAT3 activation and lowering lipid accumulation, which is regulated by SREBP1
eff↑, Sorafenib and silibinin work together to target both liver cancer cells and cancer stem cells. This combination operates by suppressing the STAT3/ERK/AKT pathways and decreasing the production of Mcl-1 and Bcl-2 proteins
CDK1↓, reducing the expression of CDK1, survivin, Bcl-xL, cyclinB1 and Mcl- 1 and simultaneously activate caspases 3 and 9
survivin↓,
CycB↓,
Mcl-1↓,
Casp9↑,
AP-1↓, hindered the activation of transcription factors NF-κB and AP-1
BioAv↑, Liang et al., created a chitosan-based lipid polymer hybrid nanoparticles that boosted the bioavailability of silymarin by 14.38-fold

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

964- SIL,    Silibinin inhibits hypoxia-induced HIF-1α-mediated signaling, angiogenesis and lipogenesis in prostate cancer cells: In vitro evidence and in vivo functional imaging and metabolomics
- vitro+vivo, Pca, LNCaP - in-vitro, Pca, 22Rv1
TumCP↓,
Hif1a↓, strongly decreased hypoxia-induced HIF-1α expression
NADPH↓,
angioG↓,
FASN↓,
ACC↓,

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.


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

Results for Effect on Cancer/Diseased Cells:
ACC↓,1,   Akt↓,1,   Akt↑,1,   angioG↓,6,   AntiCan↑,1,   AP-1↓,1,   APAF1↑,1,   Apoptosis↓,1,   Apoptosis↑,2,   AR↓,1,   ATP↓,1,   BAX↑,3,   Bcl-2↓,3,   Bcl-2↑,1,   Bcl-xL↓,2,   BIM↓,1,   BioAv↓,3,   BioAv↑,1,   CA↓,1,   Ca+2↑,1,   cardioP↑,2,   Casp↑,2,   Casp3↑,3,   pro‑Casp8↑,1,   Casp9↑,2,   CD31↓,1,   CD44↓,1,   CDK1↓,2,   CDK4↓,2,   chemoP↑,5,   ChemoSen↑,1,   i-citrate↑,1,   cMyc↓,3,   COX2↓,3,   CSCs↓,1,   CXCR4↓,2,   CycB↓,2,   cycD1↓,3,   cycE↓,1,   CYP1A1↓,1,   Cyt‑c↑,3,   Dose↝,1,   DR5↑,1,   E-cadherin↑,2,   eff↑,4,   eff↝,1,   EGFR↓,2,   EMT↓,3,   ERK↓,3,   p‑ERK↓,1,   FADD↑,1,   FAK↓,1,   Fas↑,1,   FasL↑,1,   FASN↓,1,   Foxm1↓,1,   Glycolysis↓,1,   GSH↓,1,   GSH↑,1,   Half-Life↓,1,   Half-Life↝,1,   HATs↑,2,   HDAC↓,2,   hepatoP↑,3,   HER2/EBBR2↓,1,   Hif1a↓,9,   IFN-γ↓,1,   IFN-γ↑,1,   IGFBP3↑,1,   IL1↓,2,   IL10↓,1,   IL1β↓,2,   IL2↑,1,   IL6↓,1,   Inflam↓,3,   iNOS↓,1,   p‑JNK↓,1,   lactateProd↓,1,   LC3II↑,1,   LDHA↓,1,   lipid-P↓,2,   LOX1↓,1,   MAPK↓,1,   Mcl-1↓,2,   MDR1↓,1,   MDSCs↓,1,   MEK↓,1,   miR-203↑,1,   MMP↓,3,   MMP2↓,2,   MMP9↓,2,   MMPs↓,1,   mTOR↓,1,   p‑mTOR↓,1,   N-cadherin↓,1,   NADPH↓,1,   neuroP↑,1,   NF-kB↓,3,   NHE1↓,1,   NOTCH↓,1,   NOTCH1↓,1,   OXPHOS↑,1,   P-gp↓,1,   P21↑,2,   p27↑,2,   p‑p38↓,1,   P53↑,3,   p‑P70S6K↓,1,   PCNA↓,3,   PD-L1↓,2,   PDGF↓,1,   PGE2↓,2,   PI3K↓,2,   p‑pRB↓,1,   PSA↓,2,   radioP↑,1,   Raf↓,1,   RB1↑,1,   ROS↓,1,   ROS↑,2,   selectivity↑,1,   SIRT1↓,1,   SREBP1↓,1,   STAT3↓,3,   survivin↓,4,   Telomerase↓,1,   TGF-β↓,2,   TNF-α↓,1,   toxicity↝,1,   toxicity∅,1,   TumCCA↑,3,   TumCG↓,3,   TumCI↓,1,   TumCMig↓,3,   TumCP↓,2,   tumCV↓,1,   TumMeta↓,2,   uPA↓,2,   VEGF↓,5,   VEGFR2↓,1,   Vim↓,2,   Wnt↓,2,   YAP/TEAD↓,1,   Zeb1↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 145

Results for Effect on Normal Cells:
antiOx↑,2,   BioAv↓,2,   BioAv↝,1,   Casp3↑,1,   Casp9↑,1,   COX2↓,1,   hepatoP↑,1,   Hif1a↓,3,   IL6↓,1,   IL8↓,2,   Inflam↓,2,   iNOS↓,3,   lipid-P↓,1,   MDA↓,2,   NA↓,1,   NF-kB↓,1,   NO↓,2,   PTEN↑,1,   ROS↓,2,   SIRT1↑,1,   SOD↑,1,   TAC↑,1,   TIMP1↓,1,   toxicity↓,1,   Weight↓,1,  
Total Targets: 25

Scientific Paper Hit Count for: Hif1a, HIF1α/HIF1a
12 Silymarin (Milk Thistle) silibinin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:154  Target#:143  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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