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


TGF-β, transforming growth factor-beta: Click to Expand ⟱
Source: HalifaxProj(inhibit) CGL-CS TCGA
Type:
Human malignancies frequently exhibit mutations in the TGF-β pathway, and overactivation of this system is linked to tumor growth by promoting angiogenesis and inhibiting the innate and adaptive antitumor immune responses.
Anti-inflammatory cytokine.
In normal tissues, TGF-β plays an essential role in cell cycle regulation, immune function, and tissue remodeling.
- In early carcinogenesis, TGF-β typically acts as a tumor suppressor by inhibiting cell proliferation and inducing apoptosis.

In advanced cancers, cells frequently become resistant to the growth-inhibitory effects of TGF-β.
- TGF-β then switches roles and promotes tumor progression by stimulating epithelial-to-mesenchymal transition (EMT), cell invasion, metastasis, and immune evasion.

Non-canonical (Smad-independent) pathways, such as MAPK, PI3K/Akt, and Rho signaling, also contribute to TGF-β-mediated responses.

Elevated levels of TGF-β have been detected in many advanced-stage cancers, including breast, lung, colorectal, pancreatic, and prostate cancers.
 - The switch from a tumor-suppressive to a tumor-promoting role is often associated with increased TGF-β production and activation in the tumor microenvironment.

High TGF-β expression or signaling activity is frequently correlated with aggressive disease features, resistance to therapy, increased metastasis, and poorer overall survival in many cancer types.
Scientific Papers found: Click to Expand⟱
2359- SK,    Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery
- in-vivo, Liver, NA
TumCG↓, SHK@HA-MPDA achieved tumor-targeted delivery via hyaluronic acid-mediated binding with the tumor-associated CD44, and efficiently arrested colorectal tumor growth
PKM2↓, The inhibition of PKM2 by SHK@HA-MPDA led to the remodeling of the tumor immune microenvironment
EMT↓, reversing EMT by lactate abatement and the suppression of TGFβ signaling
TGF-β↓,
Glycolysis↓, EMT reversal by suppressing glycolysis and lactate production
lactateProd↓,
ATP↓, SHK@HA-MPDA nanosystem efficiently inhibited tetramer PKM2 and further reduced lactate and ATP production

2363- SK,    Inhibition of PKM2 by shikonin impedes TGF-β1 expression by repressing histone lactylation to alleviate renal fibrosis
- in-vivo, CKD, NA
PKM2↓, In UUO mice, treatment with shikonin, a potent PKM2 inhibitor, effectively reduced lactate production, alleviated renal fibrosis, decreased TGF-β1 expression, and suppressed the MMT process.
lactateProd↓,
TGF-β↓,

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: 3

Results for Effect on Cancer/Diseased Cells:
ATP↓,1,   EMT↓,1,   Glycolysis↓,1,   lactateProd↓,2,   PKM2↓,2,   TGF-β↓,2,   TumCG↓,1,  
Total Targets: 7

Results for Effect on Normal Cells:
ARG↑,1,   eff↓,1,   IL10↑,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,1,   iNOS↓,1,   neuroP↑,1,   NF-kB↓,1,   TGF-β↑,1,   TNF-α↓,1,  
Total Targets: 11

Scientific Paper Hit Count for: TGF-β, transforming growth factor-beta
3 Shikonin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:150  Target#:304  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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