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

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


RenoP, K,Renoprotection: Click to Expand ⟱
Source:
Type:
Protects kidneys
-Same as nephroprotective
Opposite is : Nephrotoxicity is toxicity in the kidneys
Scientific Papers found: Click to Expand⟱
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)

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.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   chemoP↑,1,   Cyt‑c↑,1,   MMP↓,1,   TumCP↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 6

Results for Effect on Normal Cells:
ALAT↓,1,   antiOx↑,1,   AST↓,1,   BBB↑,1,   BioAv↑,1,   BUN↓,1,   Casp3↓,1,   creat↓,1,   Cyt‑c↓,1,   Ferroptosis↓,1,   GPx4↑,1,   GSH↑,2,   GSR↓,1,   GSTs↓,1,   Half-Life↓,1,   hepatoP↑,1,   HO-1↑,1,   IFN-γ↓,1,   IL10↓,1,   IL1β↓,1,   IL4↓,1,   Inflam↓,1,   MDA↓,1,   NRF2↑,1,   P-gp↓,1,   RenoP↑,2,   SOD↑,2,   TNF-α↓,2,  
Total Targets: 28

Scientific Paper Hit Count for: RenoP, K,Renoprotection
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:154  Target#:1175  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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