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


RadioS, RadioSensitizer: Click to Expand ⟱
Source:
Type:
A radiosensitizer is an agent that makes cancer cells more sensitive to the damaging effects of radiation therapy. By using a radiosensitizer, clinicians aim to enhance the effectiveness of radiation treatment by either increasing the damage incurred by tumor cells or by interfering with the cancer cells’ repair mechanisms. This can potentially allow for lower doses of radiation, reduced side effects, or improved treatment outcomes.
Pathways that help Radiosensitivity: downregulating HIF-1α, increase SIRT1, Txr

List of Natural Products with radiosensitizing properties:
-Curcumin:modulate NF-κB, STAT3 and has been shown in preclinical studies to enhance the effects of radiation by inhibiting cell survival pathways.
-Resveratrol:
-EGCG:
-Quercetin:
-Genistein:
-Parthenolide:

How radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including:
-gold nanoparticles (GNPs),
-gold triethylphosphine cyanide ([Au(SCN) (PEt3)]),
-auranofin, ceria nanoparticles (CONPs),
-curcumin and its derivatives,
-piperlongamide,
-indolequinone derivatives,
-micheliolide,
-motexafin gadolinium, and
-ethane selenide selenidazole derivatives (SeDs)
Scientific Papers found: Click to Expand⟱
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↓,

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


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

Results for Effect on Cancer/Diseased Cells:
angioG↓,1,   Apoptosis↑,1,   DNAdam↓,2,   MMP↓,1,   radioP↑,1,   RadioS↑,2,   ROS↓,1,   ROS↑,1,   TumCCA↑,1,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,1,  
Total Targets: 12

Results for Effect on Normal Cells:
Inflam↓,1,   radioP↑,1,   ROS↓,1,  
Total Targets: 3

Scientific Paper Hit Count for: RadioS, RadioSensitizer
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:154  Target#:1107  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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