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


HO-1, HMOX1: Click to Expand ⟱
Source:
Type:
(Also known as Hsp32 and HMOX1)
HO-1 is the common abbreviation for the protein (heme oxygenase‑1) produced by the HMOX1 gene.
HO-1 is an enzyme that plays a crucial role in various cellular processes, including the breakdown of heme, a toxic molecule. Research has shown that HO-1 is involved in the development and progression of cancer.
-widely regarded as having antioxidant and cytoprotective effects
-The overall activity of HO‑1 helps to reduce the pro‐oxidant load (by degrading free heme, a pro‑oxidant) and to generate molecules (like bilirubin) that can protect cells from oxidative damage

Studies have found that HO-1 is overexpressed in various types of cancer, including lung, breast, colon, and prostate cancer. The overexpression of HO-1 in cancer cells can contribute to their survival and proliferation by:
  Reducing oxidative stress and inflammation
  Promoting angiogenesis (the formation of new blood vessels)
  Inhibiting apoptosis (programmed cell death)
  Enhancing cell migration and invasion
When HO-1 is at a normal level, it mainly exerts an antioxidant effect, and when it is excessively elevated, it causes an accumulation of iron ions.

A proper cellular level of HMOX1 plays an antioxidative function to protect cells from ROS toxicity. However, its overexpression has pro-oxidant effects to induce ferroptosis of cells, which is dependent on intracellular iron accumulation and increased ROS content upon excessive activation of HMOX1.

-Curcumin   Activates the Nrf2 pathway leading to HO‑1 induction; known for its anti‑inflammatory and antioxidant effects.
-Resveratrol  Induces HO‑1 via activation of SIRT1/Nrf2 signaling; exhibits antioxidant and cardioprotective properties.
-Quercetin   Activates Nrf2 and related antioxidant pathways; contributes to anti‑oxidative and anti‑inflammatory responses.
-EGCG     Promotes HO‑1 expression through activation of the Nrf2/ARE pathway; also exhibits anti‑inflammatory and anticancer properties.
-Sulforaphane One of the most potent natural HO‑1 inducers; triggers Nrf2 nuclear translocation and upregulates a battery of phase II detoxifying enzymes.
-Luteolin    Induces HO‑1 via Nrf2 activation; may also exert anti‑inflammatory and neuroprotective effects in various cell models.
-Apigenin   Has been reported to induce HO‑1 expression partly via the MAPK and Nrf2 pathways; also known for anti‑inflammatory and anticancer activities.
Scientific Papers found: Click to Expand⟱
2794- CHr,    An updated review on the versatile role of chrysin in neurological diseases: Chemistry, pharmacology, and drug delivery approaches
- Review, Park, NA - Review, Stroke, NA
*neuroP↑, chrysin has protective effects against neurological conditions by modulating oxidative stress, inflammation, and apoptosis in animal models.
*ROS↓,
*Inflam↓,
*Apoptosis↓,
*IL1β↓, attenuated IL-1β and TNF-α, COX-2, iNOS, and NF-kB expression, activated JNK
*TNF-α↓,
*COX2↓,
*iNOS↓,
*NF-kB↓,
*JNK↓,
*HDAC↓, alleviated histone deacetylase (HDCA) activity, GSK-3β levels, IFNγ, IL-17,
*GSK‐3β↓,
*IFN-γ↓,
*IL17↓,
*GSH↑, increased GSH levels
*NRF2↑, Park's: Increased Nrf2, modulated HO-1, SOD, CAT, decreased MDA, inhibited NF-κB and iNOS
*HO-1↑, upregulated expression of hallmark antioxidant enzymes, including HO-1, SOD, and CAT; and decreased levels of MDA
*SOD↑,
*MDA↓,
*NO↓, Attenuated NO, increased GPx
*GPx↑,
*TBARS↓, decreased levels of TBARS, AChE, restored activities of GR, GSH, SOD, CAT and Vitamin C
*AChE↓,
*GR↑,
*Catalase↑,
*VitC↑,
*memory↑, attenuated memory impairment
*lipid-P↓, attenuated lipid peroxidation
*ROS↓, attenuated ROS

2807- CHr,    Evidence-based mechanistic role of chrysin towards protection of cardiac hypertrophy and fibrosis in rats
- in-vivo, Nor, NA
*antiOx↑, antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic
Inflam↓,
*cardioP↑, Pre-treatment with chrysin of 60 mg/kg reversed the ISO-induced damage to myocardium and prevent cardiac hypertrophy and fibrosis through various anti-inflammatory, anti-apoptotic, antioxidant and anti-fibrotic pathways
*GSH↑, CHY at the highest dose (60 mg/kg) significantly bolstered the antioxidant status :GSH, SOD and CAT
*SOD↑,
*Catalase↑,
*GAPDH↑, significant increase in GAPDH levels was observed in CHYP group in comparison with normal group
*BAX↓, Decrease in apoptotic (Bax), increase in anti-apoptotic (Bcl-2)
*Bcl-2↑,
*PARP↓, expression of downstream signalling proteins, that is, PARP, cytochrome-C and caspase-3 were following the similar pattern. however at CHY 60 mg/kg treatment group, the levels were remarkably (P < 0·001) reduced.
*Cyt‑c↓,
*Casp3↓,
*NOX4↓, Whereas, lower levels of Nox-4 and higher levels of Nrf-2, HO-1 and HSP-70 were observed in CHYP group
*NRF2↑,
*HO-1↑,
*HSP70/HSPA5↑,

2591- CHr,  doxoR,    Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway
- in-vitro, HCC, Bel-7402
NRF2↓, chrysin is a potent Nrf2 inhibitor which sensitizes BEL-7402/ADM cells to ADM
ChemoSen↑, chrysin may be an effective adjuvant sensitizer to reduce anticancer drug resistance by down-regulating Nrf2 signaling pathway.
HO-1↓, Consequently, expression of Nrf2-downstream genes HO-1, AKR1B10, and MRP5 were reduced

2590- CHr,    Chrysin suppresses proliferation, migration, and invasion in glioblastoma cell lines via mediating the ERK/Nrf2 signaling pathway
- in-vitro, GBM, T98G - in-vitro, GBM, U251 - in-vitro, GBM, U87MG
TumCP↓, Chrysin inhibited the proliferation, migration, and invasion capacity of glioblastoma cells in dose- and time-dependent manners.
TumCMig↓,
TumCI↓,
NRF2↓, chrysin deactivated the Nrf2 signaling pathway by decreasing the translocation of Nrf2 into the nucleus
HO-1↓, suppressing the expression of hemeoxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1
NADPH↓,
ERK↓, Chrysin treatment downregulates the Nrf2 pathway via inhibition of ERK signaling

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: 5

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,   ChemoSen↑,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↓,2,   Fibronectin↓,1,   GRP78/BiP↑,1,   HDAC↓,1,   Hif1a↓,1,   HK2↓,1,   HO-1↓,3,   hTERT↓,1,   IL10↓,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,1,   iNOS↓,1,   LDH↓,1,   LDL↓,1,   lipid-P↑,1,   Mcl-1↓,1,   MMP↑,1,   MMP-10↓,1,   MMP2↓,1,   MMP9↓,1,   mTOR↓,1,   NADPH↓,1,   neuroP↑,1,   NOTCH1↑,1,   NRF2↓,3,   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,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,1,   Twist↓,1,   UPR↑,1,   VEGF↓,1,   Vim↓,1,   XBP-1↓,1,   XIAP↓,1,  
Total Targets: 69

Results for Effect on Normal Cells:
AChE↓,1,   antiOx↑,1,   Apoptosis↓,1,   AST↓,1,   BAX↓,1,   Bcl-2↑,1,   cardioP↑,1,   Casp3↓,1,   Catalase↑,2,   COX2↓,2,   Cyt‑c↓,1,   GAPDH↑,1,   GPx↑,1,   GR↑,1,   GSH↑,2,   GSK‐3β↓,1,   HDAC↓,1,   HO-1↑,2,   HSP70/HSPA5↑,1,   IFN-γ↓,1,   IL17↓,1,   IL1β↓,1,   Inflam↓,1,   iNOS↓,2,   JNK↓,1,   lipid-P↓,1,   MDA↓,1,   memory↑,1,   neuroP↑,1,   NF-kB↓,2,   NO↓,1,   NOX4↓,1,   NRF2↑,2,   PARP↓,1,   ROS↓,2,   SOD↑,2,   TBARS↓,1,   TNF-α↓,1,   VitC↑,1,  
Total Targets: 39

Scientific Paper Hit Count for: HO-1, HMOX1
5 Chrysin
1 doxorubicin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:61  Target#:597  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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