Database Query Results : Luteolin, , neuroP

LT, Luteolin: Click to Expand ⟱
Features:
Luteolin a Flavonoid found in celery, parsley, broccoli, onion leaves, carrots, peppers, cabbages, apple skins, and chrysanthemum flowers.
-MDR1 expression, MMP-9, IGF-1 and Epithelial to mesenchymal transition.

*** ACTIVE WORK IN PROGRESS**

-Note half-life 2–3 hours
BioAv low, but could be improved with Res, or blend of castor oil, kolliphor and polyethylene glycol
Pathways:
- induce ROS production in cancer cell but a few reports of reduction. Always seems to reduce ROS in normal cells.
- 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↓, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, LDHA↓, HK2↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, TrxR**, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, 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⟱
2916- LT,    Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies
- Review, Var, NA - Review, AD, NA - Review, Park, NA
proCasp9↓, , by inactivating proteins; such as procaspase‐9, CDC2 and cyclin B or upregulation of caspase‐9 and caspase‐3, cytochrome C, cyclin A, CDK2, and APAF‐1, in turn inducing cell cycle
CDC2↓,
CycB↓,
Casp9↑,
Casp3↑,
Cyt‑c↑,
cycA1↑,
CDK2↓, inhibit CDK2 activity
APAF1↑,
TumCCA↑,
P53↑, enhances phosphorylation of p53 and expression level of p53‐targeted downstream gene.
BAX↑, Increasing BAX protein expression; decreasing VEGF and Bcl‐2 expression it can initiate cell cycle arrest and apoptosis.
VEGF↓,
Bcl-2↓,
Apoptosis↑,
p‑Akt↓, reduce expression levels of p‐Akt, p‐EGFR, p‐Erk1/2, and p‐STAT3.
p‑EGFR↓,
p‑ERK↓,
p‑STAT3↓,
cardioP↑, Luteolin plays positive role against cardiovascular disorders by improving cardiac function
Catalase↓, It can reduce activity levels of catalase, superoxide dismutase, and GS4
SOD↓,
*BioAv↓, bioavailability of luteolin is very low. Due to the momentous first pass effect, only 4.10% was found to be available from dosage of 50 mg/kg intake of luteolin
*antiOx↑, luteolin classically exhibits antioxidant features
*ROS↓, The antioxidant potential of luteolin and its glycosides is mainly due to scavenging activity against reactive oxygen species (ROS) and nitrogen species
*NO↓,
*GSTs↑, Luteolin may also have a role in protection and enhancement of endogenous antioxidants such as glutathione‐S‐transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT)
*GSR↑,
*SOD↑,
*Catalase↑,
*lipid-P↓, Luteolin supplementation significantly suppressed the lipid peroxidation
PI3K↓, inhibits PI3K/Akt signaling pathway to induce apoptosis
Akt↓,
CDK2↓, inhibit CDK2 activity
BNIP3↑, upregulation of BNIP3 gene
hTERT↓, Suppress hTERT in MDA‐MB‐231 breast cancer cel
DR5↑, Boost DR5 expression
Beclin-1↑, Activate beclin 1
TNF-α↓, Block TNF‐α, NF‐κB, IL‐1, IL‐6,
NF-kB↓,
IL1↓,
IL6↓,
EMT↓, Suppress EMT essentially notable in cancer metastasis
FAK↓, Block EGFR‐signaling pathway and FAK activity
E-cadherin↑, increasing E‐cadherin expression by inhibiting mdm2
MDM2↓,
NOTCH↓, Inhibit NOTCH signaling
MAPK↑, Activate MAPK to inhibit tumor growt
Vim↓, downregulation of vimentin, N‐cadherin, Snail, and induction of E‐cadherin expressions
N-cadherin↓,
Snail↓,
MMP2↓, negatively regulated MMP2 and TWIST1
Twist↓,
MMP9↓, Inhibit matrix metalloproteinase‐9 expressions;
ROS↑, Induce apoptosis, reactive oxygen development, promotion of mitochondrial autophagy, loss of mitochondrial membrane potential
MMP↓,
*AChE↓, Reduce AchE activity to slow down inception of Alzheimer's disease‐like symptoms
*MMP↑, Reverse mitochondrial membrane potential dissipation
*Aβ↓, Inhibit Aβ25‐35
*neuroP↑, reduces neuronal apoptosis; inhibits Aβ generation
Trx1↑, luteolin against human bladder cancer cell line T24 was due to induction cell‐cycle arrest at G2/M, downregulation of p‐S6, suppression of cell survival, upregulation of p21 and TRX1, reduction in ROS levels.
ROS↓,
*NRF2↑, Luteolin reduced renal injury by inhibiting XO activity, modulating uric acid transporters, as well as activating Nrf2 HO‐1/NQO1 antioxidant pathways and renal SIRT1/6 cascade.
NRF2↓, Luteolin exerted anticancer effects in HT29 cells as it inhibits nuclear factor‐erythroid‐2‐related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway
*BBB↑, Luteolin can be used to treat brain cancer due to ability of this molecule to easily cross the blood–brain barrier
ChemoSen↑, In ovarian cancer cells, luteolin chemosensitizes the cells through repressing the epithelial‐mesenchymal transition markers
GutMicro↑, Luteolin was also observed to modulate gut microbiota which reduce the number of tumors in case of colorectal cancer by enhancing the number of health‐related microbiota and reduced the microbiota related to inflammation

2912- LT,    Luteolin: a flavonoid with a multifaceted anticancer potential
- Review, Var, NA
ROS↑, induction of oxidative stress, cell cycle arrest, upregulation of apoptotic genes, and inhibition of cell proliferation and angiogenesis in cancer cells.
TumCCA↑,
TumCP↓,
angioG↓,
ER Stress↑, Luteolin induces mitochondrial dysfunction and activates the endoplasmic reticulum stress response in glioblastoma cells, which triggers the generation of intracellular reactive oxygen species (ROS)
mtDam↑,
PERK↑, activate the expression of stress-related proteins by mediating the phosphorylation of PERK, ATF4, eIF2α, and cleaved-caspase 12.
ATF4↑,
eIF2α↑,
cl‑Casp12↑,
EMT↓, Luteolin is known to reverse epithelial-to-mesenchymal transition (EMT), which is associated with the cancer cell progression and metastasis.
E-cadherin↑, upregulating the biomarker E-cadherin expression, followed by a significant downregulation of the N-cadherin and vimentin expression
N-cadherin↓,
Vim↓,
*neuroP↑, Furthermore, luteolin holds potential to improve the spinal damage and brain trauma caused by 1-methyl-4-phenylpyridinium due to its excellent neuroprotective properties.
NF-kB↓, downregulation and suppression of cellular pathways such as nuclear factor kappa B (NF-kB), phosphatidylinositol 3’-kinase (PI3K)/Akt, and X-linked inhibitor of apoptosis protein (XIAP)
PI3K↓,
Akt↑,
XIAP↓,
MMP↓, Furthermore, the membrane action potential of mitochondria depletes in the presence of luteolin, Ca2+ levels and Bax expression upregulate, the levels of caspase-3 and caspase-9 increase, while the downregulation of Bcl-2
Ca+2↑,
BAX↑,
Casp3↑,
Casp9↑,
Bcl-2↓,
Cyt‑c↑, cause the cytosolic release of cytochrome c from mitochondria
IronCh↑, Luteolin serves as a good metal-chelating agent owing to the presence of dihydroxyl substituents on the aromatic ring framework
SOD↓, luteolin further triggered an early phase accumulation of ROS due to the suppression of the activity of cellular superoxide dismutase.
*ROS↓, Luteolin reportedly demonstrated an optimal 43.7% inhibition of the accumulation of ROS, 24.5% decrease in malondialdehyde levels, and 38.7% lowering of lactate dehydrogenase levels at a concentration of 30 µM
*LDHA↑,
*SOD↑, expression of superoxide dismutase ameliorated by 73.7%, while the activity of glutathione improved by 72.3% at the same concentration of luteolin
*GSH↑,
*BioAv↓, Poor bioavailability of luteolin limits its optimal therapeutic efficacy and bioactivity
Telomerase↓, MDA-MB-231 cells with luteolin led to dose dependent arrest of cell cycle in S phase by reducing the levels of telomerase and by inhibiting the phosphorylation of NF-kB inhibitor α along with its target gene c-Myc
cMyc↓,
hTERT↓, These events led to the suppression of the expression of human telomerase reverse transcriptase (hTERT) encoding for the catalytic subunit of telomerase
DR5↑, luteolin upregulated the expression of caspase cascades and death receptors, including DR5
Fas↑, expression of proapoptotic genes such as FAS, FADD, BAX, BAD, BOK, BID, TRADD upregulates, while the anti-apoptotic genes NAIP, BCL-2, and MCL-1 experience downregulation.
FADD↑,
BAD↑,
BOK↑,
BID↑,
NAIP↓,
Mcl-1↓,
CDK2↓, expression of cell cycle regulatory genes CDK2, CDKN2B, CCNE2, CDKN1A, and CDK4 decreased on incubation with luteolin
CDK4↓,
MAPK↓, expression of MAPK1, MAPK3, MAP3K5, MAPK14, PIK3C2A, PIK3C2B, AKT1, AKT2, and ELK1 downregulated
AKT1↓,
Akt2↓,
*Beclin-1↓, luteolin led to downregulation of the expression of hypoxia-inducible factor-1α and autophagy-associated proteins, Beclin 1, and LC3
Hif1a↓,
LC3II↑, LC3-II is upregulated following the luteolin treatment in p53 wild type HepG2 cells i
Beclin-1↑, Luteolin treatment reportedly increased the number of intracellular autophagosomes, as indicated by an increased expression of Beclin 1, and conversion of LC3B-I to LC3B-II in hepatocellular carcinoma SMMC-7721 cells.

4292- LT,    Luteolin for neurodegenerative diseases: a review
- Review, AD, NA - Review, Park, NA - Review, MS, NA - Review, Stroke, NA
*Inflam↓, luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity.
*antiOx↑,
*neuroP↑,
*BioAv↝, To increase the bioavailability of luteolin, several delivery methods have been developed; the most thoroughly studied include lipid carriers like liposomes and nanoformulations
*BBB↑, luteolin given intraperitoneally (ip) to mice can readily cross the blood-brain barrier (BBB) and enter the brain
*TNF-α↓, nhibiting pro-inflammatory mediators such as cyclooxygenase-2 (COX-2), nitric oxide (NO), TNF-α, IL-β, IL-6, IL-8, IL-31, and IL-33 in several in vitro models of AD
*IL1β↓,
*IL6↓,
*IL8↓,
*IL33↓,
*NF-kB↓, inhibition of the NF-кB pathway
*BACE↓, leads to the inhibition of a downstream target– β-site amyloid precursor protein cleaving enzyme (BACE1), which is a key mediator in forming Aβ fibrils in AD pathology
*ROS↓, anti-oxidant activity mainly by reducing ROS levels and increasing SOD activity in in vitro models of AD
*SOD↑,
*HO-1↑, increase the expression of antioxidant enzymes such as heme oxygenase-1 (HO-1) via the nuclear factor erythroid 2–related factor 2/ antioxidant responsive element (Nrf-2/ARE) complex activation
*NRF2↑,
*Casp3↓, reducing the levels of caspase-3 and − 9 and improving the B-cell lymphoma protein 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, as it was reported in in vitro models of AD
*Casp9↑,
*Bax:Bcl2↓,
*UPR↑, enhancing the unfolded protein response (UPR) pathway, leading to an increase in endoplasmic reticulum (ER) chaperone GRP78 and a decrease in the expression of UPR-targeted pro-apoptotic genes via the MAPK pathway.
*GRP78/BiP↑,
*Aβ↓, evidence that suggests that luteolin can directly influence the formation of Aβ plaques by selectively inhibiting the activity of N-acetyl-α-galactosaminyltransferase (ppGalNAc-T) isoforms
*GSK‐3β↓, inactivating the glycogen synthase kinase-3 alpha (GSK-3α) isoform, suppressing Aβ and promoting tau disaggregation
*tau↓,
*CREB↑, luteolin promoted phosphorylation and activation of cAMP response element-binding protein (CREB) leading to the increased miR-132 expression, and eventually neurite outgrowth in PC12 cells
*ATP↑, ROS production was decreased by 40%, MMP levels were restored close to control N2a levels (202%), and ATP levels were improved by 444%).
*cognitive↑, protective effect of luteolin against cognitive dysfunction was also reported in the streptozotocin
*BloodF↑, Luteolin increased regional cerebral blood flow values, alleviated the leakage of the lumen of vessels, and protected the integrity of BBB
*BDNF↑, increasing the level of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor (TrkB) expression in the cerebral cortex
*TrkB↑,
*memory↑, luteolin supplementation significantly ameliorated memory and cognitive deficits in 3 × Tg-AD mice.
*PPARγ↑, attenuated mitochondrial dysfunction via peroxisome proliferator-activated receptor gamma (PPARγ) activation.
*eff↑, combination of luteolin with another compound– l-theanine (an amino acid found in tea) also improved AD-like symptoms in the Aβ25–35-treated rats

4293- LT,    Regulatory Role of NF-κB on HDAC2 and Tau Hyperphosphorylation in Diabetic Encephalopathy and the Therapeutic Potential of Luteolin
- in-vivo, Diabetic, NA
*Inflam↓, luteolin, a natural flavonoid compound with anti-inflammatory, antioxidant, and neuroprotective properties.
*antiOx↑,
*neuroP↑,
*cognitive↑, results indicated that treatment with luteolin improved the degree of cognitive impairment in mice with DE.
*p‑mTOR↓, decreased the levels of phosphorylated mTOR, phosphorylated NF-κB, and histone deacetylase 2 (HDAC2) and increased the expression of brain-derived neurotrophic factor and synaptic-related proteins
*p‑NF-kB↓,
*HDAC2↓,
*BDNF↑,
*other↓, luteolin may also directly target HDAC2, as an HDAC2 inhibitor, to alleviate DE, complementing mTOR/NF-κB signaling inhibition
*p‑tau↓, HDAC2 and tau hyperphosphorylation are regulated by the mTOR/NF-κB signaling cascade in DE, and luteolin is found to reverse these effects, demonstrating its protective role in DE

2904- LT,    Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons
- in-vitro, Park, SK-N-SH - in-vitro, AD, NA
*ROS↓, Food-derived compound luteolin possesses multitarget actions including reactive oxygen species (ROS)-scavenging activit
*neuroP↑, Upon the ROS-insulted primary neurons, luteolin concentration-dependently enhanced neuronal cell survival with efficacy higher than and potency similar to vitamin E.
*MMP↑, prevented the decreases in activities of mitochondria, catalase, and glutathione in ROS-insulted primary neurons
*Catalase↑, decreases of catalase/glutathione activity by H 2O 2 were markedly reversed following luteolin treatment.
*GSH↑,
selectivity↑, Results showed that luteolin mildly inhibited the viability of SK-N-SH cells (50% inhibition at 68.7 uM) and relatively strongly inhibited that of HuH-7 cells (50% inhibition at 14.3 uM), but did not affect that of primary neurons
*eff↑, luteolin can be designated as a potent neuroprotectant as well as suggesting that it may be effective either in the treatment of neurodegenerative diseases, such as cerebral ischemia, Parkinsons, and AD, or in the improvement of brain aging
*Cyt‑c↓, reduction of cytochrome c release from mitochondria into cytosome,


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

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   Akt↑,1,   p‑Akt↓,1,   AKT1↓,1,   Akt2↓,1,   angioG↓,1,   APAF1↑,1,   Apoptosis↑,1,   ATF4↑,1,   BAD↑,1,   BAX↑,2,   Bcl-2↓,2,   Beclin-1↑,2,   BID↑,1,   BNIP3↑,1,   BOK↑,1,   Ca+2↑,1,   cardioP↑,1,   cl‑Casp12↑,1,   Casp3↑,2,   Casp9↑,2,   proCasp9↓,1,   Catalase↓,1,   CDC2↓,1,   CDK2↓,3,   CDK4↓,1,   ChemoSen↑,1,   cMyc↓,1,   cycA1↑,1,   CycB↓,1,   Cyt‑c↑,2,   DR5↑,2,   E-cadherin↑,2,   p‑EGFR↓,1,   eIF2α↑,1,   EMT↓,2,   ER Stress↑,1,   p‑ERK↓,1,   FADD↑,1,   FAK↓,1,   Fas↑,1,   GutMicro↑,1,   Hif1a↓,1,   hTERT↓,2,   IL1↓,1,   IL6↓,1,   IronCh↑,1,   LC3II↑,1,   MAPK↓,1,   MAPK↑,1,   Mcl-1↓,1,   MDM2↓,1,   MMP↓,2,   MMP2↓,1,   MMP9↓,1,   mtDam↑,1,   N-cadherin↓,2,   NAIP↓,1,   NF-kB↓,2,   NOTCH↓,1,   NRF2↓,1,   P53↑,1,   PERK↑,1,   PI3K↓,2,   ROS↓,1,   ROS↑,2,   selectivity↑,1,   Snail↓,1,   SOD↓,2,   p‑STAT3↓,1,   Telomerase↓,1,   TNF-α↓,1,   Trx1↑,1,   TumCCA↑,2,   TumCP↓,1,   Twist↓,1,   VEGF↓,1,   Vim↓,2,   XIAP↓,1,  
Total Targets: 79

Results for Effect on Normal Cells:
AChE↓,1,   antiOx↑,3,   ATP↑,1,   Aβ↓,2,   BACE↓,1,   Bax:Bcl2↓,1,   BBB↑,2,   BDNF↑,2,   Beclin-1↓,1,   BioAv↓,2,   BioAv↝,1,   BloodF↑,1,   Casp3↓,1,   Casp9↑,1,   Catalase↑,2,   cognitive↑,2,   CREB↑,1,   Cyt‑c↓,1,   eff↑,2,   GRP78/BiP↑,1,   GSH↑,2,   GSK‐3β↓,1,   GSR↑,1,   GSTs↑,1,   HDAC2↓,1,   HO-1↑,1,   IL1β↓,1,   IL33↓,1,   IL6↓,1,   IL8↓,1,   Inflam↓,2,   LDHA↑,1,   lipid-P↓,1,   memory↑,1,   MMP↑,2,   p‑mTOR↓,1,   neuroP↑,5,   NF-kB↓,1,   p‑NF-kB↓,1,   NO↓,1,   NRF2↑,2,   other↓,1,   PPARγ↑,1,   ROS↓,4,   SOD↑,3,   tau↓,1,   p‑tau↓,1,   TNF-α↓,1,   TrkB↑,1,   UPR↑,1,  
Total Targets: 50

Scientific Paper Hit Count for: neuroP, neuroprotective
5 Luteolin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:118  Target#:1105  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page