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

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


cognitive, cognitive: Click to Expand ⟱
Source:
Type:
Cognitive


Scientific Papers found: Click to Expand⟱
3321- SIL,    cognitive_vitality_media/Silymarin-Cognitive-Vitality-For-Researchers.pdf">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

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

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↓,

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,

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↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Results for Effect on Cancer/Diseased Cells:
AChE↓,1,   antiOx↓,1,   Casp3↓,1,   cognitive↑,1,   HO-1↑,1,   Inflam↓,1,   memory↑,1,   neuroP↑,1,   NRF2↑,1,  
Total Targets: 9

Results for Effect on Normal Cells:
AChE↓,2,   Akt↑,1,   AMPK↑,1,   antiOx↓,1,   Apoptosis↓,1,   Aβ↓,2,   BBB?,1,   BChE↓,1,   BDNF↑,2,   BioAv↝,1,   Catalase↑,2,   cognitive↑,5,   COX2↓,1,   Dose↝,1,   p‑ERK↓,1,   GSH↑,3,   GutMicro↑,1,   Half-Life?,1,   hepatoP↑,2,   HO-1↑,2,   IL10↑,1,   IL1β↓,2,   IL4↓,1,   IL6↑,1,   Inflam↓,4,   iNOS↓,1,   p‑JNK↓,1,   lipid-P↓,1,   MAPK↓,2,   MDA↓,3,   memory↑,4,   MMP↑,1,   mTOR↑,1,   necrosis↓,1,   neuroP↑,4,   neuroP↝,1,   NF-kB↓,2,   NO↓,1,   NRF2↑,2,   OS↑,1,   p‑p38↓,1,   ROS↓,3,   SOD↑,2,   Strength↑,1,   tau↓,1,   TLR4↓,2,   TNF-α↓,3,  
Total Targets: 47

Scientific Paper Hit Count for: cognitive, cognitive
6 Silymarin (Milk Thistle) silibinin
1 Chemotherapy
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:154  Target#:557  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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