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


hepatoP, L,hepatoprotective: Click to Expand ⟱
Source:
Type:
Hepatoprotective is the ability of a chemical substance to prevent damage to the liver.

Grapefruit:
-hepatoprotective potential has emerged from the study of naringenin and naringin.
Blueberries/cranberries:
-proanthocyanidins
Grape:
Nopal (Cactus pear) and tuna (Cactus pear fruit) “Opuntia ficus-indica”:
Chamomile (Matricaria chamomilla or Chamomilla recutita):
Silymarin (Silybum marianum):
Blue green algae spirulina :
Propolis (bee glue):

POLYSACCHARIDES
β-glucans
Scientific Papers found: Click to Expand⟱
3042- SK,    The protective effects of Shikonin on lipopolysaccharide/D -galactosamine-induced acute liver injury via inhibiting MAPK and NF-kB and activating Nrf2/HO-1 signaling pathways
- in-vivo, Nor, NA
*TNF-α↓, Our results showed that SHK treatment distinctly decreased serum TNF-a, IL-1b, IL-6 and IFN-g inflammatory cytokine production
*IL1β↓,
*IL6↓,
*IFN-γ↓,
*ALAT↓, , reduced serum ALT, AST, hepatic MPO and ROS production levels,
*AST↓,
*MPO↓,
*ROS↓,
*JNK↓, inhibited JNK1/2, ERK1/2, p38 and NF-kB (p65) phosphorylation, and suppressed IkBa phosphorylation and degradation.
*ERK↓,
*p38↓,
*NF-kB↓,
*p‑IKKα↓,
*SOD↑, SHK could dramatically increase SOD and GSH production, as well as reduce ROS production,
*GSH↑,
*HO-1↑, through up-regulating the protein expression of HO-1, Nqo1, Gclc and Gclm, which was related to the induction of Nrf2 nuclear translocation.
*NRF2↑,
*hepatoP↑,

2415- SK,    Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways
- in-vivo, Arthritis, NA
Apoptosis?, shikonin induced apoptosis and autophagy in RA-FLSs by activating the production of reactive oxygen species (ROS) and inhibiting intracellular ATP levels, glycolysis-related proteins, and the PI3K-AKT-mTOR signaling pathway.
TumAuto↑,
ROS↑,
ATP↓,
Glycolysis↓, shikonin can inhibit RA-glycolysis in FLSs
PI3K↓,
Akt↓,
mTOR↓,
*Apoptosis↓, Shikonin can significantly reduce the expression of apoptosis-related proteins, paw swelling in rat arthritic tissues, and the levels of inflammatory factors in peripheral blood, such as TNF-α, IL-6, IL-8, IL-10, IL-17A, and IL-1β while showing less
*Inflam↓,
*TNF-α↓,
*IL6↓,
*IL8↓,
*IL10↓,
*IL17↓,
*hepatoP↑, while showing less toxicity to the liver and kidney.
*RenoP↑,
PKM2↓, The expression of glycogen proteins PKM2, GLUT1, and HK2 decreased with increasing concentrations of shikonin
GLUT1↓,
HK2↓,

2011- SK,    Shikonin Attenuates Acetaminophen-Induced Hepatotoxicity by Upregulation of Nrf2 through Akt/GSK3β Signaling
- in-vitro, Nor, HL7702 - in-vivo, Nor, NA
*NRF2↑, Shikonin (SHK) enhances Nrf2 in multiple lines of normal cells.
*hepatoP↑, SHK defended APAP-induced liver toxicity, as well as reversed the levels of serum alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO) activity, and reactive oxygen species (ROS), while it enhanced the liver glutathione (GSH) le
*ALAT↓, reversed the levels of serum alanine/aspartate aminotransferases (ALT/AST)
*AST↓,
*MPO↓,
*ROS↓, neutralized oxidative stress in APAP-treated human normal liver L-02 cells
*GSH↑, enhanced the liver glutathione (GSH) level in APAP-treated mice


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   Apoptosis?,1,   ATP↓,1,   GLUT1↓,1,   Glycolysis↓,1,   HK2↓,1,   mTOR↓,1,   PI3K↓,1,   PKM2↓,1,   ROS↑,1,   TumAuto↑,1,  
Total Targets: 11

Results for Effect on Normal Cells:
ALAT↓,2,   Apoptosis↓,1,   AST↓,2,   ERK↓,1,   GSH↑,2,   hepatoP↑,3,   HO-1↑,1,   IFN-γ↓,1,   p‑IKKα↓,1,   IL10↓,1,   IL17↓,1,   IL1β↓,1,   IL6↓,2,   IL8↓,1,   Inflam↓,1,   JNK↓,1,   MPO↓,2,   NF-kB↓,1,   NRF2↑,2,   p38↓,1,   RenoP↑,1,   ROS↓,2,   SOD↑,1,   TNF-α↓,2,  
Total Targets: 24

Scientific Paper Hit Count for: hepatoP, L,hepatoprotective
3 Shikonin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:150  Target#:1179  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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