Database Query Results : Silymarin (Milk Thistle) silibinin, ,

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">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


Scientific Papers found: Click to Expand⟱
2607- Ba,  SIL,    Baicalein Enhances the Oral Bioavailability and Hepatoprotective Effects of Silybin Through the Inhibition of Efflux Transporters BCRP and MRP2
- in-vivo, Nor, NA
*BioEnh↑, baicalein significantly increased the area under the curve (AUC) and Cmax of silybin and its conjugates, suggesting enhanced absorption in vivo.
*hepatoP↑, Moreover, coadministration of silybin with baicalein boosted the liver protective, antioxidant, and anti-inflammatory effects of silybin
*antiOx↑,
*Inflam↓,

134- CUR,  RES,  MEL,  SIL,    Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3
Apoptosis↑,
ROS↑,
Trx1↓,

3578- CUR,  SIL,    Curcumin, but not its degradation products, in combination with silibinin is primarily responsible for the inhibition of colon cancer cell proliferation
- in-vitro, CRC, DLD1
eff↑, combination of curcumin and silymarin exhibited synergistic anticancer activity.
BioAv↓, Despite the low bioavailability of curcumin and the relatively low daily dietary intake (Shen et al. 2016, Teiten et al. 2010, Tsuda 2018), the beneficial effect of curcumin observed could be due to other phytochemicals present in the diet and act sy
TumCG↓, curcumin and silibinin in combination inhibit cell growth significantly

3330- SIL,    Mechanistic Insights into the Pharmacological Significance of Silymarin
- Review, Var, NA
*neuroP↑, silymarin is employed significantly as a neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective and detoxification agent
*hepatoP↑,
*cardioP↑,
*antiOx↓,
*NLRP3↓, Zhang et al. (2018) observed that silybin significantly impedes NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in NAFLD by elevating NAD+ levels,
*NAD↑,
ROS↓, MDA-MB-231: it was observed that silybin treatment also abolishes activation of the NLRP3 inflammasome through repression of ROS generation, resulting in reduced tumor cell migration and invasion
NLRP3↓,
TumCMig↓,
*COX2↓, mpairing several enzymes (COX-2, iNOS, SGPT, SGOT, MMP, MPO, AChE, G6Pase, MAO-B, LDH, Telomerase, FAS and CK-MB)
*iNOS↓,
*MPO↓,
*AChE↓,
*LDH↓,
*Telomerase↓,
*Fas↓,

3314- SIL,    Silymarin: Unveiling its pharmacological spectrum and therapeutic potential in liver diseases—A comprehensive narrative review
- Review, NA, NA
*antiOx↑, silymarin, demonstrating remarkable antioxidant and hepatoprotective properties in extensive preclinical investigations.
*hepatoP↑, It can protect healthy liver cells or those that have not yet sustained permanent damage by reducing oxidative stress and mitigating cytotoxicity.
*Half-Life↑, The main ingredient in silymarin, silibinin, normally takes two to four hours to reach its peak plasma concentration after oral consumption, and it has a 6‐hour plasma half‐life
*ROS↓, silibinin has potent anti‐ROS qualities,
*GSH↑, silymarin, the precursor to silibinin, can increase glutathione production in the liver and hence increase the liver tissues' antioxidant capacity
*hepatoP↑, silymarin, the precursor to silibinin, can increase glutathione production in the liver and hence increase the liver tissues' antioxidant capacity
*lipid-P↓,
*TNF-α↓, inhibit the production of pro‐inflammatory cytokines, such as TNF‐α, IFN‐γ, IL‐2, and IL‐4, which are crucial in the inflammatory cascade
*IFN-γ↓,
*IL2↓,
*IL4↓,
*NF-kB↓, Silymarin's mechanism involves suppressing NF‐κB activation,
*iNOS↓, It downregulates inflammatory mediators like interleukins, TNF‐α, and iNOS, which are involved in various diseases.
*OATPs↓, Its inhibition of transporters, including OATPs and OCTs, may also affect members of the solute carrier family
*OCT4↓,
*Inflam↓, Silymarin may have anti‐inflammatory properties that limit the production of inflammatory mediators like NF‐B and inflammatory metabolites like prostaglandin E2 (PGE2)
*PGE2↓,
MMPs↓, Silymarin significantly inhibits matrix metalloproteinases (MMPs), essential for cancer metastasis,
VEGF↓, Additionally, silymarin down‐regulates VEGF expression, contributing to anti‐angiogenic effects, and has the potential to reverse STAT‐3‐associated cancer drug resistance.
angioG↓,
STAT3↓,
*ALAT↓, The research revealed improved liver function as seen by lower levels of ALT, AST, and alkaline phosphatase, as well as a considerably lower likelihood of developing DILI four weeks after starting silymarin treatment
*AST↓,
Dose↝, The suggested dosage of silymarin has been used in clinical trials for up to 48 weeks at a dose of 2100 mg/day and for up to 4 years at a dose of up to 420 mg/day.

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↓,

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↓,

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↓,

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↓,

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↓,

3324- SIL,    Silymarin prevents NLRP3 inflammasome activation and protects against intracerebral hemorrhage
*ROS↓, Silymarin (200 mg/kg) treatment 30 mins post ICH injury prevented increase in oxidative stress markers and up-regulated antioxidant status.
*TAC↑,
*NF-kB↓, Silymarin treatment significantly down regulated the inflammatory responses by suppressing NF-κB-p65 levels and inflammasome-mediated caspase-1/IL-1β expressions.
*IL2↓,
*NRF2↑, treatment with silymarin post ICH injury increased Nrf-2/HO-1 and thereby improved overall cytoprotection.
*HO-1↑,
*neuroP↑, silymarin acts as neuroprotective compound by preventing inflammatory activation and up regulating Nrf-2/HO-1 signaling post ICH injury.
*Inflam↓,
*NLRP3↓, The NLRP3 mediated inflammatory responses were down regulated during silymarin treatment post ICH injury compared to ICH group

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↓,
E2Fs↓,

3322- SIL,    Therapeutic intervention of silymarin on the migration of non-small cell lung cancer cells is associated with the axis of multiple molecular targets including class 1 HDACs, ZEB1 expression, and restoration of miR-203 and E-cadherin expression
- in-vitro, Lung, A549 - in-vitro, Lung, H1299 - in-vitro, Lung, H460
HDAC↓, associated with the inhibition of histone deacetylase (HDAC) activity and reduced levels of class 1 HDAC proteins (HDAC1, HDAC2, HDAC3 and HDAC8
HDAC1↓,
HDAC2↓,
HDAC3↓,
HDAC8↓,
HATs↑, and concomitant increases in the levels of histone acetyltransferase activity (HAT).
Zeb1↓, Treatment of A549 and H460 cells with silymarin reduced the expression of the transcription factor ZEB1 and restored expression of E-cadherin.
E-cadherin↑,
TumCMig↓, These findings indicate that silymarin can effectively inhibit lung cancer cell migration

3321- SIL,    Silymarin (Milk thistle)
- Review, AD, NA
*neuroP↝, Although silymarin is effective in several Alzheimer’s animal models, most of the proposed mechanisms of action are similar to approved drugs or drugs that have been ineffective for Alzheimer’s.
*Dose↝, Large variability in doses used, but commonly 200-600mg/day
*Half-Life?, Half-life: Six hours
*BioAv↝, (oral absorption is ~23-47%)
*cognitive↑, silibinin and silymarin improved cognition in an Alzheimer’s mouse model
*Aβ↓, Silymarin was also reported to slightly reduce Aβ plaques, Aβ oligomers, and insoluble (but not soluble) Aβ, reduce microglial inflammation, and improve cognition in an Alzheimer’s mouse model
*Inflam↓,
*OS↑, silymarin increased mean lifespan of worms by 10.1% and 24.8% at 25μM and 50μM, respectively, but had no effect at 100μM
*memory↑, (50mg/kg/day intramuscular injection) improved memory performance

3320- SIL,    Neuroprotective Potential of Silymarin against CNS Disorders: Insight into the Pathways and Molecular Mechanisms of Action
- Review, AD, NA
*hepatoP↑, Apart from the hepatoprotective nature, which is mainly due to its antioxidant and tissue regenerative properties,
*neuroP↑, Silymarin has recently been reported to be a putative neuroprotective agent against many neurologic diseases including Alzheimer's and Parkinson's diseases, and cerebral ischemia
*ROS↓, capacity to inhibit oxidative stress in the brain,
*β-Amyloid↓, additional advantages by influencing pathways such as β‐amyloid aggregation, inflammatory mechanisms, cellular apoptotic machinery, and estrogenic receptor mediation.
*Inflam↓,
*Aβ↓, Silymarin on inhibition of Aβ fibril formation and aggregation in animal and cellular models of AD
*NF-kB↓, By inhibiting the production of inflammatory agents such as NF‐κB, TNF‐α, TNF‐β, iNOS, NO, COX, Silymarin impedes neuroinflammation
*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↑, 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↑,

3318- SIL,    Pharmaceutical prospects of Silymarin for the treatment of neurological patients: an updated insight
- Review, AD, NA - Review, Park, NA
*hepatoP↑, widely studied as a hepatoprotective drug for various liver disorders.
*neuroP↑, research studies have shown its putative neuroprotective nature against various brain disorders, including psychiatric, neurodegenerative, cognitive, metabolic and other neurological disorders
*TLR4↓, Silymarin treatment has shown anti-inflammatory action in AD models by suppressing toll-like receptor 4 (TLR4) pathways and decreasing the increased mRNA levels of TNF-α, IL-1β and NF-κB
*TNF-α↓,
*IL1β↓,
*NF-kB↓,
*memory↑, improvement in memory los
*cognitive↑, finally leading to normal cognitive functions
*NRF2↑, upregulating the Nrf-2/HO-1 signaling in mice model
*HO-1↑,
*ROS↓, inhibition of oxidative stress in the brain
*Akt↑, Figure 4
*mTOR↑,
*SOD↑,
*Catalase↑,
*GSH↑,
*IL10↑,
*IL6↑,
*NO↓,
*MDA↓,
*AChE↓,
*MAPK↓,
*BDNF↑, Silymarin supplementation improved learning and memory in diabetes-induced cognitively impaired rats by elevating BDNF levels

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↑, protective effects against NDs such as Alzheimer's disease, Parkinson's disease, and depression.

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↓, Silymarin was reported to possess anti-inflammatory, antioxidant, and neuroprotective impacts.
antiOx↓,
neuroP↑,
cognitive↑, recent study shed light on the neuroprotective attributes of silymarin against cognitive dysfunction instigated in rats with doxorubicin/cyclophosphamide combination
NRF2↑, additionally, caspase-3 augmentation and of nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) pathway disturbance were found following chemotherapy treatment.
HO-1↑,
memory↑, Silymarin treatment opposed such effects via enhancing memory function, preserving brain architecture, and reducing acetylcholinesterase activity and caspase-3 level.
AChE↓,
Casp3↓,

3315- SIL,    Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats
- in-vivo, Nor, NA
neuroP↑, Silymarin protects against the brain and sciatic nerve injuries induced by docetaxel.
*NRF2↑, Silymarin activates Nrf2/HO-1, and suppresses Bax/Bcl2 signaling.
*HO-1↑,
*lipid-P↓, SLM significantly decreased brain lipid peroxidation level and ameliorated brain glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in DTX-administered rats
*GSH↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*NF-kB↓, SLM attenuated levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α),
*TNF-α↓,
*JNK↓, decreased the expression of c-Jun N-terminal kinase (JNK) in the sciatic nerve
*Bcl-2↑, SLM markedly up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and B-cell lymphoma-2 (Bcl-2) and downregulated the expression of Bcl-2 associated X protein (Bax) in the brain
*BAX↑,

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↓, Silymarin significantly reduced TNF-α and glutamate levels, and increased BDNF levels in the hippocampus of mTBI-induced male but not in female mice.
*BDNF↑,
*cognitive↑, This study demonstrates that silymarin treatment sex-dependently improves cognitive impairment in mTBI-induced mice,

3652- SIL,    Silibinin ameliorates anxiety/depression-like behaviors in amyloid β-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus
- in-vivo, NA, NA
*hepatoP↑, (Silybum marianum), has been used as a hepato-protectant in the clinical treatment of liver diseases.
*other↑, Silibinin-treatment up-regulated the function through BDNF/TrkB pathway and attenuated autophagy in the hippocampus.

109- SIL,    Silibinin induces apoptosis through inhibition of the mTOR-GLI1-BCL2 pathway in renal cell carcinoma
- vitro+vivo, RCC, 769-P - in-vitro, RCC, 786-O - in-vitro, RCC, ACHN - in-vitro, RCC, OS-RC-2
HH↓,
Gli1↓,
GLI2↓,
mTOR↓,
Bcl-2↓,

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, NA
*BDNF↑, improved BDNF expression, 5-HT, DA, NE and antioxidant paradigms in cerebral cortex as well as hippocampus.
*5HT↑,
*antiOx↑,
*IL6↓, silymarin attenuated IL-6, and TNF-α significantly in hippocampus and cerebral cortex in OBX rats.
*TNF-α↓,
*Mood↑, silymarin exhibits anti-depressant-like activity in OBX rats due to alterations in several neurotransmitters, endocrine and immunologic systems, including BDNF, 5-HT, DA, NE, MDA formation, IL-6, and TNF-α in hippocampus

4205- SIL,    The Therapeutic Effect of Silymarin and Silibinin on Depression and Anxiety Disorders and Possible Mechanism in the Brain: A Systematic Review
- Review, AD, NA
*BDNF↑, Silymarin and silibinin upregulated brain-derived neurotrophic factor (BDNF) and improved neural stem cells (NSCs) proliferation in the cortex and hippocampus.
*5HT↑, They also increased neurochemical serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels.
*MDA↓, Silymarin and silibinin reduced malondialdehyde (MDA) formation and increased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities.
*GSH↑,
*SOD↑,
*Catalase↑,
*IL6↓, silymarin and silibinin reduced interleukin (IL)-6, IL-1β, and IL-12β, reducing tumor necrosis factor α (TNF-α) induced neuroinflammation.
*IL1β↓,

4204- SIL,    Silymarin administration after cerebral ischemia improves survival of obese mice by increasing cortical BDNF and IGF1 levels
- NA, Stroke, NA
*OS↑, Silymarin treatment improved survival in both ischemic groups (non-diet control: 95.7%, HFD: 78.3%).
*BDNF↑, Silymarin raised cortical TNFα, IL4, IL10, IGF1, BDNF, and CX3CL1 levels in the HFD group with stroke, while the striatum did not present relevant differences.
*IGF-1↑,

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, NA
*MAPK↝, Silymarin utilizes a range of molecular mechanisms, including modulation of MAPK, AMPK, NF-κB, mTOR, and PI3K/Akt pathways
*AMPK↝,
*NF-kB↓,
*mTOR↝,
*PI3K↝,
*Akt↝,
*BioAv↝, silymarin faces challenges related to bioavailability and aqueous solubility, hindering its development as a clinical drug
*memory↑, silymarin dose-dependently improves the memory and expression of BDNF in TBI-induced mice along with a significant reduction in the level of glutamate and TNF-α, affirming that silymarin could be a potential therapeutic agent for addressing cognitiv
*BDNF↑,
*TNF-α↓,

3655- SIL,    Protective effect of silymarin on oxidative stress in rat brain
- in-vivo, AD, NA
*GSH↑, After SM administration GSH and AA significantly increase and SOD activity was significantly enhanced
*VitC↑,
*SOD↑,
*lipid-P↓, SM may to protect the SNC by oxidative damage for its ability to prevent lipid peroxidation and replenishing the GSH levels.
*ROS↓,
*hepatoP↑, Silybum marianum (L.) Gaertn., known as milk thistle, is one of the most popular herbal remedies for liver disease.
*neuroP↑, small number of reports of the SM effects on brain, concerning protective effect on fetal rat brain by ethanol induced injury

3654- SIL,    Effect of silymarin on biochemical parameters of oxidative stress in aged and young rat brain
- in-vivo, AD, NA
*ROS↓, Flavonoids are antioxidants found molecules capable of intercepting reactive oxygen species (ROS)
*neuroP↑, SM may contribute to the prevention of aged-related and pathological degenerative processes in the brain.
*GSH↑, silymarin induce an increase of GSH, AA levels, and SOD activity in brain of rats treated with 200 mg/kg/day for 3 day
*SOD↑,

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↑, Silibinin (silybin), a flavonoid derived from the herb milk thistle, is well known for its hepatoprotective activities.
*neuroP↑, neuroprotective effect of silibinin on Aβ25-35-injected rats
*cognitive↑, silibinin significantly attenuated Aβ25-35-induced memory deficits in Morris water maze and novel object-recognition tests.
*memory↑,
*Inflam↓, Silibinin attenuated the inflammatory responses, increased glutathione (GSH) levels and decreased malondialdehyde (MDA) levels, and upregulated autophagy levels in the Aβ25-35-injected rats.
*GSH↑,
*MDA↓,
*Inflam↓, potential candidate for AD treatment because of its anti-inflammatory, antioxidant and autophagy regulating activities.
*antiOx↓,

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.

3651- SIL,    Aminotransferase levels and silymarin in de novo tacrine-treated patients with Alzheimer's disease
- Trial, NA, NA
*hepatoP↑, Silymarin is a well-known hepatoprotective agent
*ALAT↓, Fewer patients had ALAT levels >5 ULN in the silymarin group (-33.3%).

3650- SIL,    Silibinin: a novel inhibitor of Aβ aggregation
- in-vitro, AD, SH-SY5Y
*Aβ↓, silibinin also appears to act as a novel inhibitor of Aβ aggregation and this effect showed dose-dependency.
*H2O2↓, silibinin prevented SH-SY5Y cells from injuries caused by Aβ(1-42)-induced oxidative stress by decreasing H(2)O(2) production in Aβ(1-42)-stressed neurons

3649- SIL,    Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis
*Inflam↓, anti-inflammatory, cytoprotective, and anticarcinogenic effects.
*NF-kB↓, suppression of NF-kappa B,
*cJun↓, Silymarin also inhibited the TNF-induced activation of mitogen-activated protein kinase kinase and c-Jun N-terminal kinase and abrogated TNF-induced cytotoxicity and caspase activation.
*Casp↓,
*ROS↓, Silymarin suppressed the TNF-induced production of reactive oxygen intermediates and lipid peroxidation
*lipid-P↓,

3648- SIL,    Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years
- Review, NA, NA
*antiOx↑, antioxidant, anti-inflammatory and antifibrotic power
*Inflam↓,
*lipid-P↓, reduce both lipid peroxidation and cellular necrosis.
*necrosis↓,
*hepatoP↑, silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.
*IL1↓, figure 1
*IL6↓,
*TNF-α↓,
*IFN-γ↓,
MAPK↓,
Apoptosis↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
*PPARγ↑,
*GLUT4↑,
*HSPs↓,
*HSP27↑,
*Trx↑,
*SIRT1↑,
*ALAT↓, as well as prevent ALT increase, Glutathione (GSH) decrease, lipid peroxidation and TNF-α increase
*GSH↑,
*lipid-P↓,
*TNF-α↓,
TumCG↓, silybin significantly reduces HuH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells growth by increasing cyclin-dependent kinase inhibitor p21 and p27/cyclin-dependent kinase (CDK) 4 complexes, by reducing retinoblastoma protein (Rb)-phosphorylatio
P21↑,
CDK4↑,

3647- SIL,    Silymarin Modulates Microbiota in the Gut to Improve the Health of Sow from Late Gestation to Lactation
- in-vivo, NA, NA
*IL1β↓, dietary silymarin supplementation decreased the level of pro-inflammatory cytokine IL-1β (p < 0.05) on the 18th day of lactation in the blood of the sows.
*GutMicro↝, Dietary silymarin supplementation reduced the gut bacterial community and the richness of the gut microbial community
*Inflam↓, silymarin can reduce the sow inflammatory response, improve mammary gland health, and thus improve lactation performance.

3646- SIL,    "Silymarin", a promising pharmacological agent for treatment of diseases
- Review, NA, NA
*P-gp↓, The possible known mechanisms of action of silymarin protection are blockade and adjustment of cell transporters, p-glycoprotein, estrogenic and nuclear receptors.
*Inflam↓, silymarin anti-inflammatory effects through reduction of TNF-α, protective effects on erythrocyte lysis and cisplatin-induced acute nephrotoxicity
*hepatoP↑, first usage of Milk thistle, however, was for its hepatoprotectant and antioxidant activities
*antiOx↑,
*GSH↑, increasing the glutathione concentrations
*BioAv↑, Milk thistle extract is now marketing as silymarin and silybinin capsules and tablets with an improved bioavailability under the trade names like Livergol, Silipide and Legalon
*SOD↑, increases the superoxide dismutase activity within the erythrocytes and lymphocytes (
*IFN-γ↓, enhances the IFN-γ, IL-4 and IL-10 secretion in cultures containing lymphocytes.
*IL4↓,
*IL10↓,
*Half-Life↓, Silymarin has a short half-life and quick conjugation in the liver and principal excretion in bile.
*TNF-α↓, Silybinin inhibits elevated intra-hepatic messenger RNA (mRNA) levels of IL-2, IL-4, IFN-γ, and TNF-α significantly
*ALAT↓, reduces the alanine aminotransferase and aspartate aminotransferase levels and suppressed the apoptosis in hepatocytes
*AST↓,
Akt↓, HepG2 -cells death occurs via inhibition of Akt kinase stimulated by palmitate exposure and silymarin prevents this inhibition as it has hepatoprotective activity different from its antioxidant property
chemoP↑, Silymarin can be applied as a co-treatment with the other chemotherapeutics agents while silybin is mainly useful as a hepatoprotective substance against chemotherapeutics-induced oxidative stress.
β-catenin/ZEB1↓, silymarin inhibits β-catenin increase, which will suppress the proliferation of hepatocellular carcinoma HepG2 cells.
TumCP↓,
MMP↓, mitochondrial membrane potential of HepG2 cells decreases by silymarin that causes disruption of membrane permeability so that cytochrome C transfers from the intermembrane space to the cytoplasm
Cyt‑c↑,
*RenoP↑, Renal protection
*BBB↑, silymarin has antioxidant activities in the central nervous system, which enables it to enter the CNS via the blood–brain barrier (BBB)

3333- SIL,    Silymarin attenuated nonalcoholic fatty liver disease through the regulation of endoplasmic reticulum stress proteins GRP78 and XBP-1 in mice
- in-vivo, NA, NA
*GRP78/BiP↓, silymarin attenuated NAFLD by decreasing the ER stress proteins GRP78 and XBP-1.
*XBP-1↓,

3332- SIL,    Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2
- in-vitro, Lung, A549
*antiOx↑, Silibinin is a flavonoid antioxidant and wildly used for its antihepatotoxic properties
*hepatoP↑,
MMP2↓, silibinin treatment may decrease the expressions of MMP-2 and u-PA in a concentration- and time-dependent manner and enhance the expression of TIMP-2.
uPA↓,
TIMP2↑,

2410- SIL,    Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF
- in-vitro, GBM, U87MG - in-vitro, GBM, U251 - in-vivo, NA, NA
TumAuto↑, Mechanistically, silibinin activates autophagy through depleting ATP by suppressing glycolysis.
ATP↓,
Glycolysis↓, Silibinin suppressed glycolysis in glioma cells
H2O2↑, Then, autophagy improves intracellular H2O2 via promoting p53-mediated depletion of GSH and cysteine and downregulation of xCT
P53↑,
GSH↓,
xCT↓,
BNIP3↝, The increased H2O2 promotes silibinin-induced BNIP3 upregulation and translocation to mitochondria
MMP↑, silibinin-induced mitochondrial depolarization, accumulation of mitochondrial superoxide
mt-ROS↑,
mtDam↑, Autophagy contributed to silibinin-induced mitochondria damage
HK2↓, protein levels of HK II, PFKP, and PKM2 were all downregulated time-dependently by silibinin in U87, U251, SHG-44, and C6 glioma cells
PFKP↓,
PKM2↓, silibinin suppressed glycolysis via downregulation of HK II, PFKP, and PKM2.
TumCG↓, Silibinin inhibited glioma cell growth in vivo

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

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

3292- SIL,  Fe,    Anti-tumor activity of silymarin nanoliposomes in combination with iron: In vitro and in vivo study
- in-vitro, BC, 4T1 - in-vivo, BC, 4T1
*antiOx↑, Silymarin (SLM) has been extensively investigated due to its potent antioxidant properties and demonstrated efficacy against cancer cells.
ROS↑, we hypothesized that the simultaneous administration of iron (Fe) could alter the antioxidant characteristic of SLM nanoliposomes (SLM Lip) to a prooxidant state
OS↑,
Weight↑,
TumVol↓,
eff↑, In the current study, silymarin nanoliposomes showed higher toxicity on 4 T1 cells when combined with iron sucrose.
Fenton↑, By exchanging iron species during the Fenton reaction (Fe3+ ↔ Fe2+), the ROS levels could increase

3291- SIL,    Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases
- Review, Nor, NA
*antiOx↑, Silymarin has antioxidant activities against CVDs and offers protection against oxidative stress-induced hypertension, atherosclerosis and cardiac toxicity.
*ROS↓,
*cardioP↑,
*BioAv↓, Absorption of silymarin after oral administration is rather low and peak plasma concentrations are achieved in 6 hours, in animal and humans.
*Half-Life↝, elimination half-life ranges from 6 to 8 hours.
*other↑, Rare side effects include mild gastrointestinal disturbance, nausea, and headache in clinical trials
IronCh↑, chelating metals-promoters such as Fe and Cu (2

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

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

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

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

3312- SIL,    Silymarin Alleviates Oxidative Stress and Inflammation Induced by UV and Air Pollution in Human Epidermis and Activates β-Endorphin Release through Cannabinoid Receptor Type 2
- Human, Nor, NA
*antiOx↑, silymarin (SM), an antioxidant and anti-inflammatory complex of flavonoids,
*Inflam↓,
*ROS↓, SM decreased morphological alterations, ROS, and IL-1a in UV+urban-dust-stressed RHE.
*IL1α↓,
*AhR↑, AHR- and Nrf2-related genes were upregulated, which control the antioxidant effector and barrier function.
*NRF2↑,
*IL8↓, Interleukin 8 gene expression was decreased.

2306- SIL,  CUR,  RES,  EA,    Identification of Natural Compounds as Inhibitors of Pyruvate Kinase M2 for Cancer Treatment
- in-vitro, BC, MDA-MB-231
PKM2↓, silibinin, curcumin, resveratrol, and ellagic acid as potential inhibitors of PKM2
Dose↝, IC50 values of 0.91 µM, 1.12 µM, 3.07 µM, and 4.20 µM respectively(enzymatic-assay-based screening)
Dose↝, IC50 against MDA-MB231 cells 208uM, 26uM, 306uM, 20um respectively

1316- SIL,  Chemo,    Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity
- Analysis, Var, NA
TumCCA↑, limiting the progression of cancer cells through different phases of the cycle—thus forcing them to evolve towards a process of cell death
p42↓,
P450↓,
OATPs↓, silibinin has been shown to inhibit OATP1B1, OATP1B3 and OATP2B1
chemoP↑,
ChemoSen↑,

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↓,

1140- SIL,    Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth
- in-vitro, PC, AsPC-1 - in-vivo, PC, NA - in-vitro, PC, MIA PaCa-2 - in-vitro, PC, PANC1 - in-vitro, PC, Bxpc-3
TumCG↓,
Glycolysis↓,
cMyc↓,
STAT3↓,
TumCP↓,
Weight∅, prevents the loss of body weight and muscle.
Strength↑,
DNAdam↑,
Casp3↑,
Casp9↑,
GLUT1↓,
HK2↓,
LDHA↓,
GlucoseCon↓, silibinin inhibits glucose uptake and lactate release
lactateProd↓,
PPP↓, significant reduction in pentose phosphate pathway (PPP) metabolites, including 6-phosphogluconate (~50%), erythrose-4-phosphate (~40%), sedoheptulose-7-phosphate and sedoheptulose bis-phosphate (~ 70%)
Ki-67↓, reduced Ki67-positive cells
p‑STAT3↓,
cachexia↓,

1127- SIL,    Silibinin suppresses epithelial–mesenchymal transition in human non-small cell lung cancer cells by restraining RHBDD1
- in-vitro, Lung, A549
TumCP↓,
TumCMig↓,
TumCI↓,
EMT↓,
RHBDD1↓,

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

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.

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↓,

3296- SIL,    Silibinin induces oral cancer cell apoptosis and reactive oxygen species generation by activating the JNK/c-Jun pathway
- in-vitro, Oral, Ca9-22 - in-vivo, Oral, YD10B
TumCP↓, Silibinin effectively suppressed YD10B and Ca9-22 cell proliferation and colony formation in a dose-dependent manner.
TumCCA↑, Moreover, it induced cell cycle arrest in the G0/G1 phase, apoptosis, and ROS generation in these cells.
ROS↑,
SOD1↓, silibinin downregulated SOD1 and SOD2 and triggered the JNK/c-Jun pathway in oral cancer cells.
SOD2↓,
*JNK↑, inducing apoptosis, G0/G1 arrest, ROS generation, and activation of the JNK/c-Jun pathway.
toxicity?, Silibinin significantly inhibited xenograft tumor growth in nude mice, with no obvious toxicity.
TumCMig↓, Silibinin inhibits oral cancer cell migration and invasion
TumCI↓,
N-cadherin↓, silibinin downregulated N-cadherin and vimentin expression and upregulated E-cadherin expression in YD10B and Ca9-22 cells
Vim↓,
E-cadherin↑,
EMT↓, Together, these results indicate that silibinin inhibits the migration and invasion of oral cancer cells by suppressing the EMT.
P53↑, silibinin significantly induced the expression of p53, cleaved caspase-3, cleaved PARP, and Bax, and downregulated the expression of the anti-apoptotic marker protein Bcl-2
cl‑Casp3↑,
cl‑PARP↑,
BAX↑,
Bcl-2↓,
SOD↓, silibinin inhibits SOD expression, induces ROS production, and activates the JNK/c-Jun pathway in oral cancer cells.

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, NA
*NRF2↑, silymarin activates the Nrf2/HO-1 pathway, thus providing cellular defense
*HO-1↑,
*creat↓, Silymarin diminished BPA-induced rise in serum urea, creatinine, BUN, and plasma kim-1 levels.
*BUN↓,
*RenoP↑, improved renal histoarchitecture in BPA-exposed rats.
*MDA↓, suppression of BPA-induced rise in renal iron, MDA, TNF-α, IL-1β, and cytochrome c levels, and myeloperoxidase and caspase 3 activities by silymarin therapy.
*TNF-α↓,
*IL1β↓,
*Cyt‑c↓,
*Casp3↓,
*GSTs↓, silymarin attenuated BPA-induced downregulation of Nrf2 and GSH levels, and HO-1, GPX4, SOD, catalase, GST, and GR activities.
*GSH↑,
*GPx4↑,
*SOD↑,
*GSR↓,
*Ferroptosis↓, silymarin mitigated post-weaning BPA-induced renal toxicity by suppressing ferroptosis and amyloidosis through Kim-1/Nrf2/HO-1 modulation.

3311- SIL,    Silymarin protects against acrylamide-induced neurotoxicity via Nrf2 signalling in PC12 cells
- in-vitro, Nor, PC12
*antiOx↑, Silymarin (SM) is a well-known antioxidant, anti-inflammatory and anti-cancer compound extracted from the milk thistle.
*Inflam↓,
AntiCan↑,
*ROS↓, SM could reduce ROS and MDA levels and increase GSH levels in AA-induced PC12 cells.
*MDA↓,
*GSH↓,
*NRF2↑, SM could activate Nrf2 signalling and increase the expression of Nrf2, Gpx, GCLC and GCLM in AA-treated PC12 cells.
*GPx↑,
*GCLC↑,
*GCLM↑,

3310- SIL,    Silymarin attenuates paraquat-induced lung injury via Nrf2-mediated pathway in vivo and in vitro
- in-vitro, Lung, A549
Inflam↓, silymarin administration abated PQ-induced lung histopathologic changes, decreased inflammatory cell infiltration
MPO↓, suppressed myeloperoxidase (MPO) activity and nitric oxide (NO)/inducible nitric oxide synthases (iNOS) expression,
NO↓,
iNOS↓,
ROS↓, improved oxidative stress (malondialdehyde, MDA; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GSH-Px) in lung tissue and serum.
MDA↑,
SOD↑,
Catalase↑,
GPx↑,
NRF2↑, silymarin upregulated the levels of nuclear factor-erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1(NQO1).
HO-1↑,
NADPH↑,

3309- SIL,    Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives
- Review, NA, NA
*ROS↓, (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut.
*IronCh↑,
*MMP↑, (2) Preventing free radical formation by inhibiting specific ROS-producing enzymes, or improving an integrity of mitochondria in stress conditions, are of great importance.
*NRF2↑, (3) Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation
*Inflam↓, (4) Decreasing inflammatory responses by inhibiting NF-κB pathways is an emerging mechanism of SM protective effects in liver toxicity and various liver diseases.
*hepatoP↑,
*HSPs↑, (5) Activating vitagenes, responsible for synthesis of protective molecules, including heat shock proteins (HSPs), thioredoxin and sirtuins
*Trx↑,
*SIRT2↑, increased expression of protective molecules (GSH, Thioredoxins, heat shock proteins (HSPs), sirtuins, etc.)
*GSH↑,
*ROS↑, Similarly, production of O2− and NO in isolated rat Kupffer cells were inhibited by silibinin in a dose-dependent manner, with IC50 80 μM
*NADPH↓, It also decreased the NADPH oxidase, iNOS and NF-κB over expression by As and upregulated the Nrf2 expression in the renal tissue.
*iNOS↓,
*NF-kB↓,
*BioAv↓, active free silibinin concentration in plasma after oral consumption of SM, depending on dose of supplementation, could be in the range 0.2–2.0 μM.
*Dose↝, healthy volunteers, after an oral administration of SM (equivalent to 120 mg silibinin), total (unconjugated + conjugated) silibinin concentration in plasma was 1.1–1.3 μg/mL
*BioAv↑, For example, silibinin concentration in the gut could reach 800 μM

3308- SIL,    Structural basis of Nrf2 activation by flavonolignans from silymarin
- Analysis, NA, NA
*antiOx↑, Experimental findings have suggested that the antioxidative and protective activities of these compounds could be due to their ability to activate nuclear factor erythroid 2-related factor 2 (Nrf2)
*chemoP↑,
*NRF2↑,

3307- SIL,    Flavolignans from Silymarin as Nrf2 Bioactivators and Their Therapeutic Applications
- Review, Var, NA
*NRF2↑, antioxidant and protective activities, which are probably related to the activation of the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), known as a master regulator of the cytoprotector response.
*antiOx↑, many studies have been conducted in order to identify its different biological activities, such as antioxidant, chemoprotective, anti-inflammatory,
*chemoP↑,
*Inflam↓,
*BioAv↑, The design of silybinnano-emulsions using oil, surfactants, and co-surfactants (sefsol-218/Tween 80/ethanol) in oral administration was more capable of improving the SM hepatoprotective effect than SM alone [138].
eff↑, ↑ Induction of UGT1A7 with propolis, artichoke and SM (7.3, 5 and 4.5-fold respectively
*NQO1↑, ↑ activity of NQO1
TNF-α↓, ↑ SOD and GPx activity ↓ gastric inflammation: TNF- α, IL-6 and myeloperoxidase activity,
IL6↓,
*GSH↑, PC12 cells (normal) ↑ intracellular levels of GSH ↓ levels of ROS and MDA
*ROS↓,
*MDA↓,
eff↑, combination of SM with vitamin E and/or curcumin can be a good option for the treatment of liver injury induced by toxic substances
*hepatoP↑,
*GPx↑, 50 mg/kg of SM inhibits the synthesis of lipid peroxides, promotes the upregulation of Nrf2, and the enhancement of the activity of GPx and SOD enzymes, increasing antioxidant and cytoprotective defense, thus preventing gastric oxidative stress.
*SOD↑,
*Catalase↑, treatment with SM at 200 mg/kg for 3 days improved oxidative stress by reducing MDA and increasing the activity of SOD, Cat, and GPx in lung tissue
*HO-1↑, These results were related to the upregulation of Nrf2, HO-1, and NQO1 in male Sprague-Dawley rats.
*neuroP↑, SM can exert neuroprotection against acrylamide-induced damage

3306- SIL,  Rad,    Radioprotective and radiosensitizing properties of silymarin/silibinin in response to ionizing radiation
- Review, Var, NA
radioP↑, Radioprotective and radiosensitizing properties of silymarin/silibinin in response to ionizing radiation
RadioS↑, graphical abstract
TumCMig↓, mechanisms for radiosensitization of silymarin/silibinin have been reported including suppression of migration and invasion of cancer cells, inhibition of angiogenesis, induction of apoptosis and cell cycle arrest, damage to DNA
TumCI↓,
angioG↓,
Apoptosis↑,
DNAdam↓,
ROS↑, increasing the formation of free radicals, and targeting some crucial pathways.
*ROS↓, The combination of silymarin/silibinin and irradiation decreases the toxicities caused by ionizing radiation because of their antioxidant, anti-apoptotic, anti-inflammatory and other properties.
*Inflam↓,

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↑,

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↓,

3303- SIL,    Exploring the anti-cancer and antimetastatic effect of Silymarin against lung cancer
- Review, Var, NA
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↑,

3302- SIL,    Protective effects of silymarin in glioblastoma cancer cells through redox system regulation
- in-vitro, GBM, U87MG
NRF2↑, The expression level of Nrf2 and HO-1 and glutaredoxin and thioredoxin enzymes were checked by real-time PCR method, and the expression level increased significantly after treatment.
HO-1↑,
Trx↑,
antiOx↑, Our findings suggest that silymarin may exert its cytotoxic and anticancer effects by enhancing the Nrf2/HO-1 pathway through antioxidant mechanisms in U-87 MG cells.

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.

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, NA
*ROS↓, silymarin and silibinin protect the liver from oxidative stress and sustained inflammatory processes, mainly driven by Reactive Oxygen Species (ROS) and secondary cytokines
*SOD↑, Silymarin administered to patients with chronic alcoholic liver disease significantly enhanced the low SOD activity measured in the patients’ erythrocytes and lymphocytes.
*hepatoP↑,
*AST↓, Wistar albino rats 50 mg/kg oral silymarin ↓ AST, ALT; ↓MDA (lipid peroxidation); ↑SOD, GSH, CAT; ↑GST and GR
*ALAT↓,
*lipid-P↓,
*GSH↑,
*Catalase↑,
*GSTs↑,
*GSR↑,
*TNF-α↓, ↓hepatic TNF, IFN-γ, IL-4, IL-2; ↓hepatic NF-kB activation; ↑hepatic IL-10
*IFN-γ↓,
*IL4↓,
*IL2↓,
*NF-kB↓,
*IL10↑,
*Inflam↓, Anti-Inflammatory
COX2↓, NSCLC ↓ NF-kB activation; ↓COX-2; ↑apoptosis; ↑doxorubicin efficacy
Apoptosis↑,
ChemoSen↑,
PGE2↓, ↓prostaglandin E 2
VEGF↓, ↓VEGF

3299- SIL,    Silymarin Effect on Mitophagy Pathway in the Human Colon Cancer HT-29 Cells
- in-vitro, Colon, HT29
tumCV↓, Silymarin significantly reduced the viability percentage of the HT-29 cells depending on the concentration
MMP↓, It also significantly decreased MMP in a concentration-dependent manner while significantly increased ROS formation in the HT-29 cells
ROS↑,
selectivity↑, Silymarin did not cause significant changes in the viability percentage, ROS level, and MMP of the NIH-3T3 non-cancerous cells at different concentrations.

3298- SIL,    Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells
- in-vitro, BC, MCF-7
LC3II↑, silibinin triggered the conversion of light chain 3 (LC3)-I to LC3-II, promoted the upregulation of Atg12-Atg5 formation, increased Beclin-1 expression, and decreased the Bcl-2 level.
Beclin-1↑,
Bcl-2↓,
ROS↑, Moreover, we noted elevated reactive oxygen species (ROS) generation, concomitant with the dissipation of mitochondrial transmembrane potential (ΔΨm) and a drastic decline in ATP levels following silibinin treatment,
MMP↓,
ATP↓,
eff↓, which were effectively prevented by the antioxidants, N-acetylcysteine and ascorbic acid
BNIP3?, silibinin upregulated BNIP3 protein and transcript levels
TumAuto↑, uggesting that the MCF7 cells were more sensitive to silibinin-induced autophagic cell death under the starvation condition.
eff↑, more sensitive to silibinin-induced autophagic cell death under the starvation condition.

3297- SIL,  Rad,    Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells
- in-vitro, CRC, HCT15 - in-vitro, CRC, RKO
TumCP↓, Silymarin was found to reduce proliferation of the human colon carcinoma cells in a concentration and timedependent manner.
RadioS↑, Moreover, percentage of cell death was also increased in combined treatment (20µg/ml of silymarin + radiation)
TumCCA↑, combination increases the arrest of cells in G 2 /M phase of cell cycle, DNA damage induced decrease in MMP and a decrease of the reactive oxygen species (ROS) levels, which are associated with an increase in cell death
DNAdam↓,
MMP↓,
ROS↓,
*radioP↑, Noteworthy, since silymarin was previously shown to confer protection against radiation in at least some types of normal tissues

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.

399- SNP,  SIL,    Cytotoxic potentials of silibinin assisted silver nanoparticles on human colorectal HT-29 cancer cells
- in-vitro, CRC, HT-29
P53↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 76

Results for Effect on Cancer/Diseased Cells:
ACC↓,1,   AChE↓,1,   Akt↓,3,   Akt↑,1,   p‑Akt↓,1,   Akt2↓,1,   ALAT↓,1,   angioG↓,9,   AntiCan↑,3,   antiOx↓,1,   antiOx↑,2,   AP-1↓,2,   APAF1↑,1,   Apoptosis↓,1,   Apoptosis↑,8,   AR↓,1,   AST↓,1,   ATP↓,3,   BAX↑,7,   Bcl-2↓,9,   Bcl-2↑,1,   Bcl-xL↓,3,   Beclin-1↑,1,   BID↑,1,   BIM↓,1,   BioAv↓,4,   BioAv↑,1,   BNIP3?,1,   BNIP3↝,1,   CA↓,1,   Ca+2↑,1,   cachexia↓,1,   cardioP↑,2,   Casp↑,2,   Casp3↓,1,   Casp3↑,7,   cl‑Casp3↑,1,   pro‑Casp8↑,1,   Casp9↑,7,   Catalase↑,1,   CD31↓,1,   CD44↓,1,   CDK1↓,2,   CDK2↓,1,   CDK4↓,3,   CDK4↑,1,   chemoP↑,9,   ChemoSen↑,3,   i-citrate↑,1,   cMyc↓,4,   cognitive↑,1,   COX2↓,6,   CSCs↓,1,   CXCR4↓,3,   CycB↓,2,   cycD1↓,5,   cycE↓,1,   CYP1A1↓,1,   Cyt‑c↑,5,   DNAdam↓,2,   DNAdam↑,1,   DNMT1↓,1,   Dose↝,6,   DR5↑,1,   E-cadherin↑,4,   E2Fs↓,1,   eff↓,1,   eff↑,12,   eff↝,1,   EGFR↓,2,   p‑EGFR↓,2,   EMT↓,5,   ERK↓,5,   p‑ERK↓,5,   FADD↑,1,   FAK↓,1,   Fas↑,1,   FasL↑,1,   FASN↓,1,   Fenton↑,1,   Foxm1↓,1,   Gli1↓,1,   GLI2↓,1,   GlucoseCon↓,1,   GLUT1↓,1,   Glycolysis↓,3,   GPx↑,1,   GSH↓,2,   GSH↑,1,   H2O2↑,1,   Half-Life↓,1,   Half-Life↝,2,   HATs↑,3,   HDAC↓,3,   HDAC1↓,1,   HDAC2↓,1,   HDAC3↓,1,   HDAC8↓,1,   hepatoP↑,4,   HER2/EBBR2↓,1,   HH↓,1,   HIF-1↓,1,   Hif1a↓,9,   HK2↓,2,   HO-1↑,3,   hTERT↓,1,   IFN-γ↓,1,   IFN-γ↑,1,   IGFBP3↑,1,   IL1↓,2,   IL10↓,1,   IL1β↓,2,   IL2↑,1,   IL6↓,3,   Inflam↓,9,   iNOS↓,2,   IronCh↑,2,   JAK2↓,2,   p‑JNK↓,1,   p‑JNK↑,3,   Ki-67↓,1,   lactateProd↓,2,   LC3II↑,2,   LDHA↓,2,   lipid-P↓,3,   LOX1↓,1,   MAPK↓,3,   Mcl-1↓,3,   MDA↑,1,   MDR1↓,1,   MDSCs↓,1,   MEK↓,1,   p‑MEK↓,1,   memory↑,1,   miR-155↓,1,   miR-203↑,1,   miR-21↓,1,   MMP↓,7,   MMP↑,1,   MMP2↓,4,   MMP9↓,4,   MMPs↓,2,   MPO↓,1,   mtDam↑,1,   mTOR↓,2,   p‑mTOR↓,1,   N-cadherin↓,2,   NADPH↓,1,   NADPH↑,1,   neuroP↑,3,   NF-kB↓,6,   NHE1↓,1,   NLRP3↓,1,   NO↓,1,   NOTCH↓,1,   NOTCH1↓,1,   NRF2↑,3,   OATPs↓,1,   OS↑,1,   OXPHOS↑,1,   P-gp↓,1,   P21↑,3,   p27↑,2,   p‑p38↓,2,   p‑p38↑,2,   p42↓,1,   P450↓,1,   P53↑,7,   p‑P70S6K↓,1,   cl‑PARP↑,4,   PCNA↓,3,   PD-L1↓,3,   PDGF↓,1,   PFKP↓,1,   PGE2↓,3,   PI3K↓,4,   PKM2↓,2,   PPP↓,1,   p‑pRB↓,1,   PSA↓,2,   radioP↑,4,   RadioS↑,2,   Raf↓,1,   RB1↑,1,   RHBDD1↓,1,   ROS↓,5,   ROS↑,9,   mt-ROS↑,1,   selectivity↑,2,   SIRT1↓,1,   Slug↓,1,   Snail↓,1,   SOD↓,1,   SOD↑,1,   SOD1↓,1,   SOD2↓,1,   SREBP1↓,1,   STAT3↓,7,   p‑STAT3↓,2,   STAT5↓,1,   Strength↑,1,   survivin↓,6,   Telomerase↓,1,   TGF-β↓,2,   TIMP2↑,1,   TNF-α↓,3,   toxicity?,1,   toxicity↝,1,   toxicity∅,1,   Trx↑,1,   Trx1↓,1,   TumAuto↑,2,   TumCCA↑,9,   TumCD↑,1,   TumCG↓,7,   TumCI↓,4,   TumCMig↓,9,   TumCP↓,10,   tumCV↓,4,   TumMeta↓,4,   TumVol↓,3,   uPA↓,3,   VEGF↓,8,   VEGFR2↓,1,   Vim↓,3,   Weight↑,1,   Weight∅,1,   Wnt↓,2,   Wnt/(β-catenin)↓,1,   xCT↓,1,   YAP/TEAD↓,1,   Zeb1↓,3,   α-SMA↓,1,   β-catenin/ZEB1↓,2,  
Total Targets: 234

Results for Effect on Normal Cells:
5HT↑,2,   5LO↓,1,   ACC↓,1,   AChE↓,3,   AhR↑,1,   Akt↑,1,   Akt↝,1,   ALAT↓,5,   AMPK↑,1,   AMPK↝,1,   antiOx↓,2,   antiOx↑,15,   Apoptosis↓,1,   AST↓,4,   Aβ↓,4,   BAX↑,1,   BBB?,1,   BBB↑,1,   BChE↓,1,   Bcl-2↑,1,   BDNF↑,6,   BioAv↓,4,   BioAv↑,3,   BioAv↝,4,   BioEnh↑,1,   BUN↓,1,   cardioP↑,2,   Casp↓,1,   Casp3↓,1,   Casp3↑,1,   Casp9↑,1,   Catalase↑,6,   chemoP↑,3,   cJun↓,1,   cognitive↑,5,   COX2↓,5,   creat↓,1,   Cyt‑c↓,1,   Dose↝,2,   eff↑,1,   EGFR↓,1,   p‑ERK↓,2,   Fas↓,1,   FASN↓,1,   Ferroptosis↓,1,   GCLC↑,1,   GCLM↑,1,   glucose↓,1,   GLUT4↑,1,   GPx↑,3,   GPx4↑,1,   GRP78/BiP↓,1,   GSH↓,1,   GSH↑,15,   GSR↓,1,   GSR↑,1,   GSTs↓,1,   GSTs↑,2,   GutMicro↑,1,   GutMicro↝,1,   H2O2↓,1,   Half-Life?,1,   Half-Life↓,1,   Half-Life↑,1,   Half-Life↝,1,   hepatoP↑,20,   Hif1a↓,3,   HO-1↑,6,   HSP27↑,1,   HSPs↓,1,   HSPs↑,1,   IFN-γ↓,4,   IGF-1↑,1,   IL1↓,1,   IL10↓,1,   IL10↑,2,   IL1α↓,1,   IL1β↓,5,   IL2↓,3,   IL4↓,4,   IL6↓,4,   IL6↑,1,   IL8↓,3,   Inflam↓,22,   iNOS↓,9,   IronCh↑,1,   JNK↓,1,   JNK↑,1,   p‑JNK↓,1,   LDH↓,1,   lipid-P?,1,   lipid-P↓,9,   MAPK↓,3,   MAPK↝,1,   MDA↓,9,   memory↑,5,   MMP↑,2,   Mood↑,1,   MPO↓,1,   mTOR↑,1,   mTOR↝,1,   NA↓,1,   NAD↑,1,   NADPH↓,1,   necrosis↓,2,   neuroP↑,13,   neuroP↝,1,   NF-kB↓,13,   NLRP3↓,3,   NO↓,4,   NQO1↑,1,   NRF2↑,10,   OATPs↓,1,   OCT4↓,1,   OS↑,2,   other↑,2,   P-gp↓,1,   p38↓,1,   p‑p38↓,1,   PGE2↓,1,   PI3K↝,1,   PPARγ↑,1,   PTEN↑,1,   radioP↑,2,   RenoP↑,2,   ROS↓,21,   ROS↑,1,   SIRT1↑,2,   SIRT2↑,1,   SOD↑,12,   Strength↑,1,   TAC↑,2,   tau↓,1,   Telomerase↓,1,   TGF-β↓,1,   TIMP1↓,1,   TLR4↓,2,   TNF-α↓,13,   TNF-β↓,1,   toxicity↓,1,   toxicity∅,1,   Trx↑,2,   VitC↑,1,   Weight↓,1,   XBP-1↓,1,   α-SMA↓,1,   α-SMA↝,1,   β-Amyloid↓,1,  
Total Targets: 148

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:154  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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