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


neuroP, neuroprotective: Click to Expand ⟱
Source:
Type:
Neuroprotective refers to the ability of a substance, intervention, or strategy to preserve the structure and function of nerve cells (neurons) against injury or degeneration.
-While cancer and neurodegenerative processes might seem distinct, there is significant overlap in terms of treatment-related neurotoxicity, shared molecular mechanisms, and the potential for therapies that provide neuroprotection during cancer treatment.
Scientific Papers found: Click to Expand⟱
3050- SK,    Systemic administration of Shikonin ameliorates cognitive impairment and neuron damage in NPSLE mice
- in-vivo, Nor, NA
*Inflam↓, Shikonin relieved the progression of NPSLE by suppressing neuroinflammation.
*neuroP↑, Shikonin repaired the loss of neuronal synapses in NPSLE mice.
*cognitive↑, Shikonin ameliorates cognitive impairment

3049- SK,    Shikonin Attenuates Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment by Inhibiting Apoptosis via PTEN/Akt/CREB/BDNF Signaling
- in-vivo, Nor, NA - NA, Stroke, NA
*neuroP↑, Shikonin (SK) exerts neuroprotective effects
*p‑PTEN↓, SK administration reversed the upregulation of p-PTEN and the downregulation of p-Akt, p-CREB, and BDNF
*p‑Akt↑,
*Bcl-2↑, SK treatment upregulated the expression of bcl-2 and downregulated the expression of bax, thereby elevating the bcl-2/bax ratio.
*BAX↓,
*cognitive↑, , consequently improving cognitive impairment.

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↝,

2214- SK,    Shikonin Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Activating Nrf2-ARE Signaling Pathway
- in-vitro, Nor, NA
*NRF2↑, shikonin can increase the expression of Nrf2 and its downstream molecules HO-1 and NQO1, thereby enhancing the antioxidant capacity of SGNs and SGSs
*HO-1↑,
*NQO1↑,
*antiOx↑,
*neuroP↑, shikonin pretreatment has a defensive effect on auditory nerve damage.
*ROS↓, shikonin pretreatment can also significantly reduce the high levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in SGNs caused by ouabain, and increase the levels of superoxide dismutase (SOD) and reduced glutathione (GSH) expression
*MDA↓,
*SOD↑,
GSH↑,

2213- SK,    Shikonin attenuates cerebral ischemia/reperfusion injury via inhibiting NOD2/RIP2/NF-κB-mediated microglia polarization and neuroinflammation
- in-vivo, Stroke, NA
*neuroP↑, Shikonin treatment significantly reduced brain infarction volume and improved neurological function in MCAO/R rats.
*Inflam↓, Shikonin treatment significantly reduced microglial proinflammatory phenotype and levels of proinflammatory markers (inducible-NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α),
*iNOS↓,
*TNF-α↓,
*IL1β↓, interleukin-1 beta (IL-1β), and IL-6), increased microglial anti-inflammatory phenotype and levels of anti-inflammatory markers (Arginase-1 (Arg1), transforming growth factor-beta (TGF-β), and IL-10),
*IL6↓,
*ARG↑,
*TGF-β↑,
*IL10↑,
*NF-kB↓, reversed the expression of Nucleotide-binding oligomerization domain 2 (NOD2) and phosphorylation receptor interacting protein 2 (p-RIP2), and suppressed nuclear factor kappa-B (NF-κB) signaling activation in the ischemic penumbra regions.
*eff↓, Furthermore, overexpression of NOD2 markedly attenuated the neuroprotective effects of Shikonin treatment in MCAO/R rats.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Results for Effect on Cancer/Diseased Cells:
AntiCan↑,1,   Apoptosis↑,1,   cardioP↑,1,   Cyt‑c↑,1,   DNAdam↑,1,   GSH↑,1,   LDH↝,1,   MMP↓,1,   Necroptosis↑,1,   NF-kB↓,1,   PKM2↓,1,   ROS↑,1,   TumCCA↑,1,  
Total Targets: 13

Results for Effect on Normal Cells:
p‑Akt↑,1,   antiOx↑,2,   ARG↑,1,   BAX↓,2,   Bcl-2↑,2,   BioAv↓,1,   BioAv↑,2,   Catalase↑,1,   cognitive↑,2,   COX2↓,1,   eff↓,1,   GPx↑,1,   Half-Life↝,1,   HO-1↑,1,   IL10↑,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,3,   iNOS↓,1,   MDA↓,1,   MPO↓,1,   neuroP↑,5,   NF-kB↓,1,   NF-kB↑,1,   NQO1↑,1,   NRF2↑,1,   other↑,1,   p‑PTEN↓,1,   ROS↓,2,   SOD↑,2,   STAT3↑,1,   TGF-β↑,1,   TNF-α↓,2,  
Total Targets: 33

Scientific Paper Hit Count for: neuroP, neuroprotective
5 Shikonin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:150  Target#:1105  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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