condition found tbRes List
SK, Shikonin: Click to Expand ⟱
Features:
The (R)-enantiomer of alkannin is known as shikonin, and the racemic mixture of the two is known as shikalkin.
Shikonin is a naphthoquinone derivative primarily isolated from the roots of plants in the Boraginaceae family (e.g., Lithospermum erythrorhizon).
Shikonin is the main active component of a Chinese medicinal plant 'Zi Cao'
-Shikonin is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with anti-inflammatory properties
-Quinone methides (QMs) are highly reactive intermediates formed from natural compounds like shikonin
-ic50 cancer cells 1-10uM, normal cells >10uM

-known as Glycolysis inhibitor: ( inhibit pyruvate kinase M2 (PKM2*******), a key enzyme in the glycolytic pathway)

Available from mcsformulas.com Shikonin Pro Liposomal, 30 mg
Also In Glycolysis Inhibithree(100 mg PHLORIZIN,10 mg TANSHINONE IIA, 8 mg Shikonin)

-Note half-life15-30mins or 8hr?.
BioAv low, poor water solubility
Pathways:
- usually induce ROS production in cancer cells, and reduce ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ GPx4↓
- 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↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK, P53↑,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


cardioP, cardioProtective: Click to Expand ⟱
Source:
Type:
CardioProtective


Scientific Papers found: Click to Expand⟱
3040- SK,    Pharmacological Properties of Shikonin – A Review of Literature since 2002
- Review, Var, NA - Review, IBD, NA - Review, Stroke, NA
*Half-Life↝, One study using H-shikonin in mice showed that shikonin was rapidly absorbed after oral and intramuscular administration, with a half-life in plasma of 8.79 h and a distribution volume of 8.91 L/kg.
*BioAv↓, shikonin is generally used in creams and ointments, that is, oil-based preparations; indeed, its insolubility in water is usually the cause of its low bioavailability
*BioAv↑, 200-fold increase in the solubility, photostability, and in vitro permeability of shikonin through the formation of a 1 : 1 inclusion complex with hydroxypropyl-β-cyclodextrin.
*BioAv↑, 181-fold increase in the solubility of shikonin in aqueous media in the presence of β-lactoglobulin at a concentra- tion of 3.1 mg/mL
*Inflam↓, anti-inflammatory effect of shikonin
*TNF-α↓, shikonin inhibited TNF-α production in LPS-stimulated rat primary macrophages as well as NF-κB translocation from the cytoplasm to the nucleus.
*other↑, authors found that treatment with shikonin prevented the shortening of the colorectum and decreased weight loss by 5 % while improving the ap- pearance of feces and preventing bloody stools.
*MPO↓, MPO activity was reduced as well as the expression of COX-2, the activation of NF-κB and that of STAT3.
*COX2↓,
*NF-kB↑,
*STAT3↑,
*antiOx↑, Antioxidant Effects of Shikonin
*ROS↓, radical scavenging activity of shikonin
*neuroP↑, shown to exhibit a neuroprotective effect against the damage caused by ischemia/reperfusion in adult male Kunming mice
*SOD↑, it also attenuated neuronal damage and the upregulation of superoxide dismutase, catalase, and glutathione peroxidase activities while reducing the glutathione/glutathione disulfide ratio.
*Catalase↑,
*GPx↑,
*Bcl-2↑, shikonin upregulated Bcl-2, downregulated Bax and prevented cell nuclei from undergoing morphological changes typical of apoptosis.
*BAX↓,
cardioP↑, Two different studies have suggested a possible cardioprotective effect of shikonin that would be related to its anti-inflammatory and antioxidant effects.
AntiCan↑, A wide spectrum of anticancer mechanisms of action have been described for shikonin:
NF-kB↓, suppression of NF-κB-regulated gene products [44],
ROS↑, ROS generation [46],
PKM2↓, inhibition of tumor-specific pyruvate kinase-M2 [47,48]
TumCCA↑, cell cycle arrest [49]
Necroptosis↑, or induction of necroptosis [50],
Apoptosis↑, shikonin at 1 μM induced caspase-dependent apoptosis in U937 cells after 6 h with an increase in DNA fragmentation, intracellular ROS, low mitochondrial membrane potential
DNAdam↑,
MMP↓,
Cyt‑c↑, At 10 μM, shikonin induced a greater release of cytochrome c from the mitochondria and of lactate dehydrogenase,
LDH↝,

2215- SK,  doxoR,    Shikonin alleviates doxorubicin-induced cardiotoxicity via Mst1/Nrf2 pathway in mice
- in-vivo, Nor, NA
*cardioP↑, Mice receiving shikonin showed reduced cardiac injury response and enhanced cardiac function after DOX administration
*ROS↓, Shikonin significantly attenuated DOX-induced oxidative damage, inflammation accumulation and cardiomyocyte apoptosis.
*Inflam↓,
*Mst1↓, Shikonin protects against DOX-induced cardiac injury by inhibiting Mammalian sterile 20-like kinase 1 (Mst1) and oxidative stress and activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
*NRF2↑,
*eff↓, Nrf2 knockdown counteracted the protective effects of shikonin on cardiac injury and dysfunction caused by DOX in mice
*antiOx↑, Previous studies have shown that shikonin possesses direct and indirect antioxidant properties, as evidenced by its ability to restore SOD expression and GSH levels, as well as block oxidative stress
*SOD↑,
*GSH↑,
*TNF-α↓, shikonin decreased the elevlated cardiac TNF-α induced by DOX
BAX↓, Shikonin attenuated DOX-induced upregulation of Bax and the down-regulation of Bcl-2
Bcl-2↑,


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

Results for Effect on Cancer/Diseased Cells:
AntiCan↑,1,   Apoptosis↑,1,   BAX↓,1,   Bcl-2↑,1,   cardioP↑,1,   Cyt‑c↑,1,   DNAdam↑,1,   LDH↝,1,   MMP↓,1,   Necroptosis↑,1,   NF-kB↓,1,   PKM2↓,1,   ROS↑,1,   TumCCA↑,1,  
Total Targets: 14

Results for Effect on Normal Cells:
antiOx↑,2,   BAX↓,1,   Bcl-2↑,1,   BioAv↓,1,   BioAv↑,2,   cardioP↑,1,   Catalase↑,1,   COX2↓,1,   eff↓,1,   GPx↑,1,   GSH↑,1,   Half-Life↝,1,   Inflam↓,2,   MPO↓,1,   Mst1↓,1,   neuroP↑,1,   NF-kB↑,1,   NRF2↑,1,   other↑,1,   ROS↓,2,   SOD↑,2,   STAT3↑,1,   TNF-α↓,2,  
Total Targets: 23

Scientific Paper Hit Count for: cardioP, cardioProtective
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:150  Target#:1188  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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