condition found tbRes List
CHr, Chrysin: Click to Expand ⟱
Features:
Chrysin is found in passion flower and honey. It is a flavonoid.
-To reach plasma levels that might more closely match the concentrations used in in vitro studies (typically micromolar), considerably high doses or advanced delivery mechanisms would be necessary.

-Note half-life 2 hrs, BioAv very poor
Pathways:
Graphical Pathways

- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, GSH↓ HO1↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMP2↓, MMP9↓, TIMP2, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, cMyc↓, GLUT1↓, LDH↓, HK2↓, PDKs↓, HK2↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓,
- Others: PI3K↓, AKT↓, STAT↓, Wnt↓, AMPK↓, ERK↓, JNK, TrxR,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


LDH, Lactate Dehydrogenase: Click to Expand ⟱
Source:
Type:
LDH is a general term that refers to the enzyme that catalyzes the interconversion of lactate and pyruvate. LDH is a tetrameric enzyme, meaning it is composed of four subunits.
LDH refers to the enzyme as a whole, while LDHA specifically refers to the M subunit. Elevated LDHA levels are often associated with poor prognosis and aggressive tumor behavior, similar to elevated LDH levels.

However, it's worth noting that some studies have shown that LDHA is a more specific and sensitive biomarker for cancer than total LDH, as it is more closely associated with the Warburg effect and cancer metabolism.

Dysregulated LDH activity contributes significantly to cancer development, promoting the Warburg effect (Chen et al., 2007), which involves increased glucose uptake and lactate production, even in the presence of oxygen, to meet the energy demands of rapidly proliferating cancer cells (Warburg and Minami, 1923; Dai et al., 2016b). LDHA overexpression favors pyruvate to lactate conversion, leading to tumor microenvironment acidification and aiding cancer progression and metastasis.

Inhibitors:
Flavonoids, a group of polyphenols abundant in fruit, vegetables, and medicinal plants, function as LDH inhibitors.

• Galloflavin: A flavonoid compound found in the plant Galphimia gracilis, which has been shown to inhibit LDH and have anti-cancer activity.
• Fisetin: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity.
• Quercetin: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity.
• Kaempferol: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity.
• Resveratrol: A polyphenol compound found in grapes and other plants, which has been shown to inhibit LDH and have anti-cancer activity.
• Curcumin: A polyphenol compound found in turmeric, which has been shown to inhibit LDH and have anti-cancer activity.
• Berberine: A compound found in the plant Berberis, which has been shown to inhibit LDH and have anti-cancer activity.
• Honokiol: A lignan compound found in the plant Magnolia, which has been shown to inhibit LDH and have anti-cancer activity.
• Silibinin: A flavonoid compound found in milk thistle, which has been shown to inhibit LDH and have anti-cancer activity.
Others:Ursolic acid, Oleanolic acid, Limonin, Allicin (garlic), Taurine
Scientific Papers found: Click to Expand⟱
2785- CHr,    Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin
- Review, Var, NA
*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1↓,
hTERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   ALAT↓,1,   ALP↓,1,   angioG↓,1,   Bcl-xL↓,1,   BioAv↑,1,   Ca+2↑,1,   cardioP↑,1,   Casp3↑,1,   CLDN1↓,1,   COX2↑,1,   cycD1↓,1,   Cyt‑c↑,1,   DNAdam↑,1,   E-cadherin↑,1,   eff↑,2,   EGFR↓,1,   p‑eIF2α↑,1,   EMT↓,1,   ER Stress↑,1,   ERK↓,1,   Fibronectin↓,1,   GRP78/BiP↑,1,   HDAC↓,1,   Hif1a↓,1,   HK2↓,1,   HO-1↓,1,   hTERT↓,1,   IL10↓,1,   IL1β↓,1,   IL6↓,1,   iNOS↓,1,   LDH↓,1,   LDL↓,1,   lipid-P↑,1,   Mcl-1↓,1,   MMP↑,1,   MMP-10↓,1,   MMP2↓,1,   MMP9↓,1,   mTOR↓,1,   neuroP↑,1,   NOTCH1↑,1,   NRF2↓,1,   PARP↑,1,   PDK1↓,1,   PGE2↓,1,   PPARα↓,1,   RenoP↑,1,   ROS↑,1,   Slug↓,1,   Snail↓,1,   STAT3↓,1,   TET1↑,1,   TLR4↓,1,   TNF-α↓,1,   TOP1↓,1,   Twist↓,1,   UPR↑,1,   VEGF↓,1,   Vim↓,1,   XBP-1↓,1,   XIAP↓,1,  
Total Targets: 63

Results for Effect on Normal Cells:
AST↓,1,   COX2↓,1,   iNOS↓,1,   NF-kB↓,1,  
Total Targets: 4

Scientific Paper Hit Count for: LDH, Lactate Dehydrogenase
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:61  Target#:906  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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