Database Query Results : Luteolin, ,

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


Scientific Papers found: Click to Expand⟱
1539- Api,  LT,    Dietary flavones counteract phorbol 12-myristate 13-acetate-induced SREBP-2 processing in hepatic cells
- in-vitro, Liver, HepG2
"highlight2" >SREBP2↓, ecreased transcription of SREBP-2 upon the apigenin treatment
"highlight2" >eff↑, 25 lM of both flavones could significantly bring down the induced pMEK and pERK.
"highlight2" >p‑MEK↓,
"highlight2" >p‑ERK↓,

2596- Api,  LT,    Natural Nrf2 Inhibitors: A Review of Their Potential for Cancer Treatment
- Review, Var, NA
"highlight2" >NRF2↓, In addition, natural compounds such as apigenin, luteolin, chrysin and brusatol have been shown to be potent Nrf2 inhibitors.
"highlight2" >chemoP↑, These findings suggest that natural Nrf2 inhibitors could be utilized as chemopreventive and chemotherapeutic agents, as well as tumor sensitizers for conventional radiotherapy and chemotherapy.

2625- Ba,  LT,    Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocyte
- in-vivo, Stroke, NA
"highlight2" >*lipid-P↓, Baicalein and luteolin prevented the Fe-SP-induced lipid peroxidation in rat neonatal cardiomyocytes.
"highlight2" >*ACSL4∅, Baicalein and luteolin can reduce the protein levels of ACSL4 and Nrf2, and enhance the protein levels of GPX4 in ischemia/reperfusion-treated rat hearts.
"highlight2" >*NRF2∅, Our results suggest that BAI and Lut prevented the I/R-induced increased of ACSL4, NRF2, and HO-1 protein
"highlight2" >*GPx4∅, BAI and Lut prevented the I/R-induced increased of ACSL4, NRF2, and HO-1 protein, and the I/R-decreased GPX4 protein levels
"highlight2" >*Ferroptosis↓, BAI was found to suppress ferroptosis in cancer cells via reducing reactive oxygen species (ROS) generation.
"highlight2" >*ROS↓,
"highlight2" >*MDA↓, Moreover, both BAI and Lut decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers
"highlight2" >*eff↑, BAI and Lut reduced the I/R-induced myocardium infarction
"highlight2" >*HO-1∅, Our results suggest that BAI and Lut prevented the I/R-induced increased of ACSL4, NRF2, and HO-1 protein

3633- BBR,  LT,  Croc,  QC,    Naturally Occurring Acetylcholinesterase Inhibitors and Their Potential Use for Alzheimer's Disease Therapy
- Review, AD, NA
"highlight2" >*AChE↓, Alzheimer's disease (AD) is a main cause of dementia, accounting for up to 75% of all dementia cases. Pathophysiological processes described for AD progression involve neurons and synapses degeneration, mainly characterized by cholinergic impairment.
"highlight2" >*AChE↓, Fig1: Berberine(1uM), Luteolin(80uM), Crocetin(100uM), Quercetin(120uM)

2917- LT,  Rad,    Luteolin acts as a radiosensitizer in non‑small cell lung cancer cells by enhancing apoptotic cell death through activation of a p38/ROS/caspase cascade
- in-vitro, Lung, NA
"highlight2" >Bcl-2↓, Combined treatment with luteolin and IR enhanced apoptotic cell death in association with downregulation of B‑cell lymphoma 2 (Bcl‑2) and activation of caspase‑3, ‑8, and ‑9; it also induced phosphorylation of MAPK and ROS accumulation
"highlight2" >Casp3↑,
"highlight2" >Casp8↑,
"highlight2" >Casp9↑,
"highlight2" >p‑p38↑,
"highlight2" >ROS↑,
"highlight2" >RadioS↑, luteolin acts as a radiosensitizer by enhancing apoptotic cell death through activation of a p38/ROS/caspase cascade

2922- LT,    Combination of transcriptomic and proteomic approaches helps unravel the mechanisms of luteolin in inducing liver cancer cell death via targeting AKT1 and SRC
- in-vitro, Liver, HUH7
"highlight2" >Half-Life↝, However, after oral administration, luteolin showed relatively rapid absorption and slow elimination in rats, with a tmax (time to reach peak plasma level) of approximately 1.02 h and a t1/2 (elimination half-life) of 4.94 h, indicating that luteolin
"highlight2" >TumCCA↑, luteolin could promote cell cycle arrest and apoptosis in HuH-7 cells
"highlight2" >AKT1↓, Dramatic downregulation of components downstream of the AKT1-ASK2-ATF2 pathway (CycD, BCL2, CycA, etc.), the AKT1-NF-κB pathway (BCL-XL and MIP2) and the AKT1-GSK3β-β-catenin pathway (c-Myc and CCND1)
"highlight2" >ATF2↓,
"highlight2" >NF-kB↓,
"highlight2" >GSK‐3β↓,
"highlight2" >cMyc↓,
"highlight2" >GSTs↓, expression change of NQO-1, GSTs, and TRXR1 indicated the increase in ROS
"highlight2" >TrxR1↓,
"highlight2" >ROS↑,

2921- LT,    Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies
- Review, Nor, NA
"highlight2" >*hepatoP↑, Due to its excellent liver protective effect, luteolin is an attractive molecule for the development of highly promising liver protective drugs.
"highlight2" >*AMPK↑, fig2
"highlight2" >*SIRT1↑,
"highlight2" >*ROS↓,
"highlight2" >STAT3↓,
"highlight2" >TNF-α↓,
"highlight2" >NF-kB↓,
"highlight2" >*IL2↓,
"highlight2" >*IFN-γ↓,
"highlight2" >*GSH↑,
"highlight2" >*SREBP1↓,
"highlight2" >*ZO-1↑,
"highlight2" >*TLR4↓,
"highlight2" >BAX↑, anti cancer
"highlight2" >Bcl-2↓,
"highlight2" >XIAP↓,
"highlight2" >Fas↑,
"highlight2" >Casp8↑,
"highlight2" >Beclin-1↑,
"highlight2" >*TXNIP↓, luteolin inhibited TXNIP, caspase-1, interleukin-1β (IL-1β) and IL-18 to prevent the activation of NLRP3 inflammasome, thereby alleviating liver injury.
"highlight2" >*Casp1↓,
"highlight2" >*IL1β↓,
"highlight2" >*IL18↓,
"highlight2" >*NLRP3↓,
"highlight2" >*MDA↓, inhibiting oxidative stress and regulating the level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)
"highlight2" >*SOD↑,
"highlight2" >*NRF2↑, luteolin promoted the activation of the Nrf2/ antioxidant response element (ARE) pathway and NF-κB cell apoptosis pathway, thereby reversing the decrease in Nrf2 levels(lead induced liver injury)
"highlight2" >*ER Stress↓, down regulate the formation of nitrotyrosine (NT) and endoplasmic reticulum (ER) stress induced by acetaminophen, and alleviate liver injury
"highlight2" >*ALAT↓, ↓ALT, AST, MDA, iNOS, NLRP3 ↑GSH, SOD, Nrf2
"highlight2" >*AST↓,
"highlight2" >*iNOS↓,
"highlight2" >*IL6↓, ↓TXNIP, NLRP3, TNF-α, IL-6 ↑HO-1, NQO1
"highlight2" >*HO-1↑,
"highlight2" >*NQO1↑,
"highlight2" >*PPARα↑, ↓TNF-α, IL-6 IL-1β, Bax ↑PPARα
"highlight2" >*ATF4↓, ↓ALT, AST, TNF-α, IL-6, MDA, ATF-4, CHOP ↑GSH, SOD
"highlight2" >*CHOP↓,
"highlight2" >*Inflam↓, Luteolin ameliorates MAFLD through anti-inflammatory and antioxidant effects
"highlight2" >*antiOx↑,
"highlight2" >*GutMicro↑, luteolin could significantly enrich more than 10% of intestinal bacterial species, thereby increasing the abundance of ZO-1, down regulating intestinal permeability and plasma lipopolysaccharide

2920- LT,    Formulation, characterization, in vitro and in vivo evaluations of self-nanoemulsifying drug delivery system of luteolin
- in-vitro, Nor, NA - in-vivo, Nor, NA
"highlight2" >BioAv↑, optimized formula exhibited approximately 83, 17 and 3-fold enhancement in the solubility in vitro release and ex vivo permeation respectively.
"highlight2" >eff↑, Based on the results obtained in this study, we conclude that castor oil, kolliphor and PEG 200 in a proportion of 10:45:45% v/v, respectively, produced an optimum preconcentrate of SNEDDS formulation for solubility and permeability improveme

2919- LT,    Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence
- Review, Var, NA
"highlight2" >RadioS↑, it can be used as an adjuvant to radio-chemotherapy and helps to ameliorate cancer complications
"highlight2" >ChemoSen↑,
"highlight2" >chemoP↑,
"highlight2" >*lipid-P↓, ↓LPO, ↑CAT, ↑SOD, ↑GPx, ↑GST, ↑GSH, ↓TNF-α, ↓IL-1β, ↓Caspase-3, ↑IL-10
"highlight2" >*Catalase↑,
"highlight2" >*SOD↑,
"highlight2" >*GPx↑,
"highlight2" >*GSTs↑,
"highlight2" >*GSH↑,
"highlight2" >*TNF-α↓,
"highlight2" >*IL1β↓,
"highlight2" >*Casp3↓,
"highlight2" >*IL10↑,
"highlight2" >NRF2↓, Lung cancer model ↓Nrf2, ↓HO-1, ↓NQO1, ↓GSH
"highlight2" >HO-1↓,
"highlight2" >NQO1↓,
"highlight2" >GSH↓,
"highlight2" >MET↓, Lung cancer model ↓MET, ↓p-MET, ↓p-Akt, ↓HGF
"highlight2" >p‑MET↓,
"highlight2" >p‑Akt↓,
"highlight2" >HGF/c-Met↓,
"highlight2" >NF-kB↓, Lung cancer model ↓NF-κB, ↓Bcl-XL, ↓MnSOD, ↑Caspase-8, ↑Caspase-3, ↑PARP
"highlight2" >Bcl-2↓,
"highlight2" >SOD2↓,
"highlight2" >Casp8↑,
"highlight2" >Casp3↑,
"highlight2" >PARP↑,
"highlight2" >MAPK↓, LLC-induced BCP mouse model ↓p38 MAPK, ↓GFAP, ↓IBA1, ↓NLRP3, ↓ASC, ↓Caspase1, ↓IL-1β
"highlight2" >NLRP3↓,
"highlight2" >ASC↓,
"highlight2" >Casp1↓,
"highlight2" >IL6↓, Lung cancer model ↓TNF‑α, ↓IL‑6, ↓MuRF1, ↓Atrogin-1, ↓IKKβ, ↓p‑p65, ↓p-p38
"highlight2" >IKKα↓,
"highlight2" >p‑p65↓,
"highlight2" >p‑p38↑,
"highlight2" >MMP2↓, Lung cancer model ↓MMP-2, ↓ICAM-1, ↓EGFR, ↓p-PI3K, ↓p-Akt
"highlight2" >ICAM-1↓,
"highlight2" >EGFR↑,
"highlight2" >p‑PI3K↓,
"highlight2" >E-cadherin↓, Lung cancer model ↑E-cadherin, ↑ZO-1, ↓N-cadherin, ↓Claudin-1, ↓β-Catenin, ↓Snail, ↓Vimentin, ↓Integrin β1, ↓FAK
"highlight2" >ZO-1↑,
"highlight2" >N-cadherin↓,
"highlight2" >CLDN1↓,
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >Snail↓,
"highlight2" >Vim↑,
"highlight2" >ITGB1↓,
"highlight2" >FAK↓,
"highlight2" >p‑Src↓, Lung cancer model ↓p-FAK, ↓p-Src, ↓Rac1, ↓Cdc42, ↓RhoA
"highlight2" >Rac1↓,
"highlight2" >Cdc42↓,
"highlight2" >Rho↓,
"highlight2" >PCNA↓, Lung cancer model ↓Cyclin B1, ↑p21, ↑p-Cdc2, ↓Vimentin, ↓MMP9, ↑E-cadherin, ↓AIM2, ↓Pro-caspase-1, ↓Caspase-1 p10, ↓Pro-IL-1β, ↓IL-1β, ↓PCNA
"highlight2" >Tyro3↓, Lung cancer model ↓TAM RTKs, ↓Tyro3, ↓Axl, ↓MerTK, ↑p21
"highlight2" >AXL↓,
"highlight2" >CEA↓, B(a)P induced lung carcinogenesis ↓CEA, ↓NSE, ↑SOD, ↑CAT, ↑GPx, ↑GR, ↑GST, ↑GSH, ↑Vitamin E, ↑Vitamin C, ↓PCNA, ↓CYP1A1, ↓NF-kB
"highlight2" >NSE↓,
"highlight2" >SOD↓,
"highlight2" >Catalase↓,
"highlight2" >GPx↓,
"highlight2" >GSR↓,
"highlight2" >GSTs↓,
"highlight2" >GSH↓,
"highlight2" >VitE↓,
"highlight2" >VitC↓,
"highlight2" >CYP1A1↓,
"highlight2" >cFos↑, Lung cancer model ↓Claudin-2, ↑p-ERK1/2, ↑c-Fos
"highlight2" >AR↓, ↓Androgen receptor
"highlight2" >AIF↑, Lung cancer model ↑Apoptosis-inducing factor protein
"highlight2" >p‑STAT6↓, ↓p-STAT6, ↓Arginase-1, ↓MRC1, ↓CCL2
"highlight2" >p‑MDM2↓, Lung cancer model ↓p-PI3K, ↓p-Akt, ↓p-MDM2, ↑p-P53, ↓Bcl-2, ↑Bax
"highlight2" >NOTCH1↓, Lung cancer model ↑Bax, ↑Cleaved-caspase 3, ↓Bcl2, ↑circ_0000190, ↓miR-130a-3p, ↓Notch-1, ↓Hes-1, ↓VEGF
"highlight2" >VEGF↓,
"highlight2" >H3↓, Lung cancer model ↑Caspase 3, ↑Caspase 7, ↓H3 and H4 HDAC activities
"highlight2" >H4↓,
"highlight2" >HDAC↓,
"highlight2" >SIRT1↓, Lung cancer model ↑Bax/Bcl-2, ↓Sirt1
"highlight2" >ROS↑, Lung cancer model ↓NF-kB, ↑JNK, ↑Caspase 3, ↑PARP, ↑ROS, ↓SOD
"highlight2" >DR5↑, Lung cancer model ↑Caspase-8, ↑Caspase-3, ↑Caspase-9, ↑DR5, ↑p-Drp1, ↑Cytochrome c, ↑p-JNK
"highlight2" >Cyt‑c↑,
"highlight2" >p‑JNK↑,
"highlight2" >PTEN↓, Lung cancer model 1/5/10/30/50/80/100 μmol/L ↑Cleaved caspase-3, ↑PARP, ↑Bax, ↓Bcl-2, ↓EGFR, ↓PI3K/Akt/PTEN/mTOR, ↓CD34, ↓PCNA
"highlight2" >mTOR↓,
"highlight2" >CD34↓,
"highlight2" >FasL↑, Lung cancer model ↑DR 4, ↑FasL, ↑Fas receptor, ↑Bax, ↑Bad, ↓Bcl-2, ↑Cytochrome c, ↓XIAP, ↑p-eIF2α, ↑CHOP, ↑p-JNK, ↑LC3II
"highlight2" >Fas↑,
"highlight2" >XIAP↓,
"highlight2" >p‑eIF2α↑,
"highlight2" >CHOP↑,
"highlight2" >LC3II↑,
"highlight2" >PD-1↓, Lung cancer model ↓PD-L1, ↓STAT3, ↑IL-2
"highlight2" >STAT3↓,
"highlight2" >IL2↑,
"highlight2" >EMT↓, Luteolin exerts anticancer activity by inhibiting EMT, and the possible mechanisms include the inhibition of the EGFR-PI3K-AKT and integrin β1-FAK/Src signaling pathways
"highlight2" >cachexia↓, luteolin could be a potential safe and efficient alternative therapy for the treatment of cancer cachexi
"highlight2" >BioAv↑, A low-energy blend of castor oil, kolliphor and polyethylene glycol 200 increases the solubility of luteolin by a factor of approximately 83
"highlight2" >*Half-Life↝, ats administered an intraperitoneal injection of luteolin (60 mg/kg) absorbed it rapidly as well, with peak levels reached at 0.083 h (71.99 ± 11.04 μg/mL) and a prolonged half-life (3.2 ± 0.7 h)
"highlight2" >*eff↑, Luteolin chitosan-encapsulated nano-emulsions increase trans-nasal mucosal permeation nearly 6-fold, drug half-life 10-fold, and biodistribution of luteolin in brain tissue 4.4-fold after nasal administration

2918- LT,    Luteolin inhibits melanoma growth in vitro and in vivo via regulating ECM and oncogenic pathways but not ROS
- in-vitro, Melanoma, A375 - in-vivo, Melanoma, NA - in-vitro, Melanoma, SK-MEL-28
"highlight2" >TumCG↓, Luteolin inhibited melanoma tumor growth in vitro and in vivo.
"highlight2" >ROS↑, Luteolin induced ROS in melanoma cells but ROS was not the cause of growth inhibition.
"highlight2" >ECM/TCF↓, luteolin inhibited ECM pathway, oncogenic pathway and modulated immune signaling.

2911- LT,    Luteolin targets MKK4 to attenuate particulate matter-induced MMP-1 and inflammation in human keratinocytes
- in-vitro, Nor, HaCaT
"highlight2" >*MMP1↓, luteolin effectively suppressed PM-induced MMP-1 and COX-2 expression and reduced the production of the proinflammatory cytokine IL-6.
"highlight2" >*COX2↓,
"highlight2" >*IL6↓,
"highlight2" >*AP-1↓, luteolin inhibited the activation of AP-1 and NF-κB pathways and decreased reactive oxygen species (ROS) levels in HaCaT cells.
"highlight2" >*NF-kB↓,
"highlight2" >*ROS↓,
"highlight2" >*p‑MKK4↑, luteolin binds directly to mitogen-activated protein kinase kinase (MKK) 4, inhibiting its kinase activity . increases phosphorylation of MKK4
"highlight2" >*p‑JNK↓, subsequently reducing the phosphorylation of JNK1/2 and p38 mitogen-activated protein kinase.
"highlight2" >*p‑p38↓,

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
"highlight2" >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
"highlight2" >CDC2↓,
"highlight2" >CycB↓,
"highlight2" >Casp9↑,
"highlight2" >Casp3↑,
"highlight2" >Cyt‑c↑,
"highlight2" >cycA1↑,
"highlight2" >CDK2↓, inhibit CDK2 activity
"highlight2" >APAF1↑,
"highlight2" >TumCCA↑,
"highlight2" >P53↑, enhances phosphorylation of p53 and expression level of p53‐targeted downstream gene.
"highlight2" >BAX↑, Increasing BAX protein expression; decreasing VEGF and Bcl‐2 expression it can initiate cell cycle arrest and apoptosis.
"highlight2" >VEGF↓,
"highlight2" >Bcl-2↓,
"highlight2" >Apoptosis↑,
"highlight2" >p‑Akt↓, reduce expression levels of p‐Akt, p‐EGFR, p‐Erk1/2, and p‐STAT3.
"highlight2" >p‑EGFR↓,
"highlight2" >p‑ERK↓,
"highlight2" >p‑STAT3↓,
"highlight2" >cardioP↑, Luteolin plays positive role against cardiovascular disorders by improving cardiac function
"highlight2" >Catalase↓, It can reduce activity levels of catalase, superoxide dismutase, and GS4
"highlight2" >SOD↓,
"highlight2" >*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
"highlight2" >*antiOx↑, luteolin classically exhibits antioxidant features
"highlight2" >*ROS↓, The antioxidant potential of luteolin and its glycosides is mainly due to scavenging activity against reactive oxygen species (ROS) and nitrogen species
"highlight2" >*NO↓,
"highlight2" >*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)
"highlight2" >*GSR↑,
"highlight2" >*SOD↑,
"highlight2" >*Catalase↑,
"highlight2" >*lipid-P↓, Luteolin supplementation significantly suppressed the lipid peroxidation
"highlight2" >PI3K↓, inhibits PI3K/Akt signaling pathway to induce apoptosis
"highlight2" >Akt↓,
"highlight2" >CDK2↓, inhibit CDK2 activity
"highlight2" >BNIP3↑, upregulation of BNIP3 gene
"highlight2" >hTERT↓, Suppress hTERT in MDA‐MB‐231 breast cancer cel
"highlight2" >DR5↑, Boost DR5 expression
"highlight2" >Beclin-1↑, Activate beclin 1
"highlight2" >TNF-α↓, Block TNF‐α, NF‐κB, IL‐1, IL‐6,
"highlight2" >NF-kB↓,
"highlight2" >IL1↓,
"highlight2" >IL6↓,
"highlight2" >EMT↓, Suppress EMT essentially notable in cancer metastasis
"highlight2" >FAK↓, Block EGFR‐signaling pathway and FAK activity
"highlight2" >E-cadherin↑, increasing E‐cadherin expression by inhibiting mdm2
"highlight2" >MDM2↓,
"highlight2" >NOTCH↓, Inhibit NOTCH signaling
"highlight2" >MAPK↑, Activate MAPK to inhibit tumor growt
"highlight2" >Vim↓, downregulation of vimentin, N‐cadherin, Snail, and induction of E‐cadherin expressions
"highlight2" >N-cadherin↓,
"highlight2" >Snail↓,
"highlight2" >MMP2↓, negatively regulated MMP2 and TWIST1
"highlight2" >Twist↓,
"highlight2" >MMP9↓, Inhibit matrix metalloproteinase‐9 expressions;
"highlight2" >ROS↑, Induce apoptosis, reactive oxygen development, promotion of mitochondrial autophagy, loss of mitochondrial membrane potential
"highlight2" >MMP↓,
"highlight2" >*AChE↓, Reduce AchE activity to slow down inception of Alzheimer's disease‐like symptoms
"highlight2" >*MMP↑, Reverse mitochondrial membrane potential dissipation
"highlight2" >*Aβ↓, Inhibit Aβ25‐35
"highlight2" >*neuroP↑, reduces neuronal apoptosis; inhibits Aβ generation
"highlight2" >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.
"highlight2" >ROS↓,
"highlight2" >*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.
"highlight2" >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
"highlight2" >*BBB↑, Luteolin can be used to treat brain cancer due to ability of this molecule to easily cross the blood–brain barrier
"highlight2" >ChemoSen↑, In ovarian cancer cells, luteolin chemosensitizes the cells through repressing the epithelial‐mesenchymal transition markers
"highlight2" >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

2915- LT,    Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells
- in-vitro, Colon, HT29 - in-vitro, CRC, SNU-407 - in-vitro, Nor, FHC
"highlight2" >DNMTs↓, luteolin inhibited the expression of DNA methyltransferases, a transcription repressor, and increased the expression and activity of ten-eleven translocation (TET) DNA demethylases,
"highlight2" >TET1↑,
"highlight2" >NRF2↑, luteolin decreased the methylation of the Nrf2 promoter region, which corresponded to the increased mRNA expression of Nrf2
"highlight2" >HDAC↓, Recently, Zao et al. demonstrated that luteolin epigenetically activates the Nrf2 pathway by downregulating DNA methyltransferase (DNMT) and histone deacetylase (HDAC) expression
"highlight2" >tumCV↓, Luteolin decreased the viability of all three cell lines in a dose-dependent manner
"highlight2" >BAX↑, luteolin upregulated the expression of the apoptotic protein Bax, active caspase-9, and active caspase-3, while it downregulated the expression of the anti-apoptotic protein Bcl-2,
"highlight2" >Casp9↑,
"highlight2" >Casp3↑,
"highlight2" >Bcl-2↓,
"highlight2" >ROS↓, Luteolin promotes ROS scavenging by inducing the expression of antioxidant enzymes
"highlight2" >GSS↑, luteolin increased the protein expression of the antioxidant enzymes GCLc, GSS, catalase, and HO-1 in a dose- and time-dependent manner
"highlight2" >Catalase↑,
"highlight2" >HO-1↑,
"highlight2" >DNMT1↓, Luteolin markedly decreased the protein expression of DNMT1, DNMT3A, and DNMT3B in a dose- and time-dependent manner
"highlight2" >DNMT3A↓,
"highlight2" >TET1↑, In contrast, it markedly increased the protein expression of TET1, TET2, and TET3 in a dose- and time-dependent manner
"highlight2" >TET3↑,
"highlight2" >TET2↓,
"highlight2" >P53↑, Luteolin upregulated the expression of p53 and its target p21 in a dose- and time-dependent manner
"highlight2" >P21↑,

2914- LT,    Therapeutic Potential of Luteolin on Cancer
- Review, Var, NA
"highlight2" >*antiOx↑, As an antioxidant, Luteolin and its glycosides can scavenge free radicals caused by oxidative damage and chelate metal ions
"highlight2" >*IronCh↑,
"highlight2" >*toxicity↓, The safety profile of Luteolin has been proven by its non-toxic side effects, as the oral median lethal dose (LD50) was found to be higher than 2500 and 5000 mg/kg in mice and rats, respectively, equal to approximately 219.8−793.7 mg/kg in humans
"highlight2" >*BioAv↓, One major problem related to the use of flavonoids for therapeutic purposes is their low bioavailability.
"highlight2" >*BioAv↑, Resveratrol, which functions as the inhibitor of UGT1A1 and UGT1A9, significantly improved the bioavailability of Luteolin by decreasing the major glucuronidation metabolite in rats
"highlight2" >DNAdam↑, Luteolin’s anticancer properties, which involve DNA damage, regulation of redox, and protein kinases in inhibiting cancer cell proliferation
"highlight2" >TumCP↓,
"highlight2" >DR5↑, Luteolin was discovered to promote apoptosis of different cancer cells by increasing Death receptors, p53, JNK, Bax, Cleaved Caspase-3/-8-/-9, and PARP expressions
"highlight2" >P53↑,
"highlight2" >JNK↑,
"highlight2" >BAX↑,
"highlight2" >cl‑Casp3↑,
"highlight2" >cl‑Casp8↑,
"highlight2" >cl‑Casp9↑,
"highlight2" >cl‑PARP↑,
"highlight2" >survivin↓, downregulating proteins involved in cell cycle progression, including Survivin, Cyclin D1, Cyclin B, and CDC2, and upregulating p21
"highlight2" >cycD1↓,
"highlight2" >CycB↓,
"highlight2" >CDC2↓,
"highlight2" >P21↑,
"highlight2" >angioG↓, suppress angiogenesis in cancer cells by inhibiting the expression of some angiogenic factors, such as MMP-2, AEG-1, VEGF, and VEGFR2
"highlight2" >MMP2↓,
"highlight2" >AEG1↓,
"highlight2" >VEGF↓,
"highlight2" >VEGFR2↓,
"highlight2" >MMP9↓, inhibit metastasis by inhibiting several proteins that function in metastasis, such as MMP-2/-9, CXCR4, PI3K/Akt, ERK1/2
"highlight2" >CXCR4↓,
"highlight2" >PI3K↓,
"highlight2" >Akt↓,
"highlight2" >ERK↓,
"highlight2" >TumAuto↑, can promote the conversion of LC3B I to LC3B II and upregulate Beclin1 expression, thereby causing autophagy
"highlight2" >LC3B-II↑,
"highlight2" >EMT↓, Luteolin was identified to suppress the epithelial to mesenchymal transition by upregulating E-cadherin and downregulating N-cadherin and Wnt3 expressions.
"highlight2" >E-cadherin↑,
"highlight2" >N-cadherin↓,
"highlight2" >Wnt↓,
"highlight2" >ROS↑, DNA damage that is induced by reactive oxygen species (ROS),
"highlight2" >NICD↓, Luteolin can block the Notch intracellular domain (NICD) that is created by the activation of the Not
"highlight2" >p‑GSK‐3β↓, Luteolin can inhibit the phosphorylation of the GSK3β induced by Wnt, resulting in the prevention of GSK3β inhibition
"highlight2" >iNOS↓, Luteolin in colon cancer and the complications associated with it, particularly the decreasing effect on the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)
"highlight2" >COX2↓,
"highlight2" >NRF2↑, Luteolin has been identified to increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a crucial transcription factor with anticarcinogenic properties related
"highlight2" >Ca+2↑, caused loss of the mitochondrial membrane action potential, enhanced levels of mitochondrial calcium (Ca2+),
"highlight2" >ChemoSen↑, Luteolin enhanced the effect of one of the most effective chemotherapy drugs, cisplatin, on CRC cells
"highlight2" >ChemoSen↓, high dose of Luteolin application negatively affected the oxaliplatin-based chemotherapy in a p53-dependent manner [52]. They suggested that the flavonoids with Nrf2-activating ability might interfere with the chemotherapeutic efficacy of anticancer
"highlight2" >IFN-γ↓, decreased the expression of interferon-gamma-(IFN-γ)
"highlight2" >RadioS↑, suggested that Luteolin can act as a radiosensitizer, promoting apoptosis by inducing p38/ROS/caspase cascade
"highlight2" >MDM2↓, Luteolin treatment was associated with increased p53 and p21 and decreased MDM4 expressions both in vitro and in vivo.
"highlight2" >NOTCH1↓, Luteolin suppressed the growth of lung cancer cells, metastasis, and Notch-1 signaling pathway
"highlight2" >AR↓, downregulating the androgen receptor (AR) expression
"highlight2" >TIMP1↑, Luteolin inhibits the migration of U251MG and U87MG human glioblastoma cell lines by downregulating MMP-2 and MMP-9 and upregulating the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2.
"highlight2" >TIMP2↑,
"highlight2" >ER Stress↑, Luteolin caused oxidative stress and ER stress in the Hep3B cells,
"highlight2" >CDK2↓, Luteolin’s ability to decrease Akt, polo-like kinase 1 (PLK1), cyclin B1, cyclin A, CDC2, cyclin-dependent kinase 2 (CDK2) and Bcl-xL
"highlight2" >Telomerase↓, Luteolin dose-dependently inhibited the telomerase levels and caused the phosphorylation of NF-κB and the target gene of NF-κB, c-Myc to suppress the human telomerase reverse transcriptase (hTERT)
"highlight2" >p‑NF-kB↑,
"highlight2" >p‑cMyc↑,
"highlight2" >hTERT↓,
"highlight2" >RAS↓, Luteolin was found to suppress the expressions of K-Ras, H-Ras, and N-Ras, which are the activators of PI3K
"highlight2" >YAP/TEAD↓, Luteolin caused significant inhibition of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)
"highlight2" >TAZ↓,
"highlight2" >NF-kB↓, Luteolin was found to have a strong inhibitory effect on the NF-κB
"highlight2" >NRF2↓, Luteolin-loaded nanoparticles resulted in a significant reduction in the Nrf2 levels compared to Luteolin alone.
"highlight2" >HO-1↓, The expressions of the downstream genes of Nrf2, Ho1, and MDR1 were also reduced, where inhibition of Nrf2 expression significantly increased the cell death of breast cancer cells
"highlight2" >MDR1↓,

2913- LT,    Luteolin induces apoptosis by impairing mitochondrial function and targeting the intrinsic apoptosis pathway in gastric cancer cells
- in-vitro, GC, HGC27 - in-vitro, BC, MCF-7 - in-vitro, GC, MKN45
"highlight2" >TumCP↓, Luteolin inhibited the proliferation of gastric cancer HGC-27, MFC and MKN-45 cells
"highlight2" >MMP↓, impaired mitochondrial integrity and function by destroying the mitochondrial membrane potential,
"highlight2" >Apoptosis↑, eventually leading to apoptosis of gastric cancer HGC-27, MFC and MKN-45 cells
"highlight2" >ROS↑, luteolin-induced ROS accumulation in HGC-27, MFC and MKN-45 cells. HGC-27 and MFC cells were treated with luteolin (10, 40, and 70 µM) for 24 h, and MKN-45 cells were treated for 48 h
"highlight2" >SOD↓, suggested that luteolin could induce SOD activity reduction, especially in the high dose of luteolin groups in HGC-27 and MFC cells
"highlight2" >ATP↓, ATP content decreased, especially in the high-dose groups
"highlight2" >Bax:Bcl2↑, luteolin significantly decreased the ratio between Bcl-2 and Bax in HGC-27, MFC, and MKN-45 cells
"highlight2" >TumCCA↑, In addition, it is reported that luteolin could induce cell cycle arrest and apoptosis through extrinsic and intrinsic signaling pathways in MCF-7 breast cancer cell

2912- LT,    Luteolin: a flavonoid with a multifaceted anticancer potential
- Review, Var, NA
"highlight2" >ROS↑, induction of oxidative stress, cell cycle arrest, upregulation of apoptotic genes, and inhibition of cell proliferation and angiogenesis in cancer cells.
"highlight2" >TumCCA↑,
"highlight2" >TumCP↓,
"highlight2" >angioG↓,
"highlight2" >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)
"highlight2" >mtDam↑,
"highlight2" >PERK↑, activate the expression of stress-related proteins by mediating the phosphorylation of PERK, ATF4, eIF2α, and cleaved-caspase 12.
"highlight2" >ATF4↑,
"highlight2" >eIF2α↑,
"highlight2" >cl‑Casp12↑,
"highlight2" >EMT↓, Luteolin is known to reverse epithelial-to-mesenchymal transition (EMT), which is associated with the cancer cell progression and metastasis.
"highlight2" >E-cadherin↑, upregulating the biomarker E-cadherin expression, followed by a significant downregulation of the N-cadherin and vimentin expression
"highlight2" >N-cadherin↓,
"highlight2" >Vim↓,
"highlight2" >*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.
"highlight2" >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)
"highlight2" >PI3K↓,
"highlight2" >Akt↑,
"highlight2" >XIAP↓,
"highlight2" >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
"highlight2" >Ca+2↑,
"highlight2" >BAX↑,
"highlight2" >Casp3↑,
"highlight2" >Casp9↑,
"highlight2" >Bcl-2↓,
"highlight2" >Cyt‑c↑, cause the cytosolic release of cytochrome c from mitochondria
"highlight2" >IronCh↑, Luteolin serves as a good metal-chelating agent owing to the presence of dihydroxyl substituents on the aromatic ring framework
"highlight2" >SOD↓, luteolin further triggered an early phase accumulation of ROS due to the suppression of the activity of cellular superoxide dismutase.
"highlight2" >*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
"highlight2" >*LDHA↑,
"highlight2" >*SOD↑, expression of superoxide dismutase ameliorated by 73.7%, while the activity of glutathione improved by 72.3% at the same concentration of luteolin
"highlight2" >*GSH↑,
"highlight2" >*BioAv↓, Poor bioavailability of luteolin limits its optimal therapeutic efficacy and bioactivity
"highlight2" >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
"highlight2" >cMyc↓,
"highlight2" >hTERT↓, These events led to the suppression of the expression of human telomerase reverse transcriptase (hTERT) encoding for the catalytic subunit of telomerase
"highlight2" >DR5↑, luteolin upregulated the expression of caspase cascades and death receptors, including DR5
"highlight2" >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.
"highlight2" >FADD↑,
"highlight2" >BAD↑,
"highlight2" >BOK↑,
"highlight2" >BID↑,
"highlight2" >NAIP↓,
"highlight2" >Mcl-1↓,
"highlight2" >CDK2↓, expression of cell cycle regulatory genes CDK2, CDKN2B, CCNE2, CDKN1A, and CDK4 decreased on incubation with luteolin
"highlight2" >CDK4↓,
"highlight2" >MAPK↓, expression of MAPK1, MAPK3, MAP3K5, MAPK14, PIK3C2A, PIK3C2B, AKT1, AKT2, and ELK1 downregulated
"highlight2" >AKT1↓,
"highlight2" >Akt2↓,
"highlight2" >*Beclin-1↓, luteolin led to downregulation of the expression of hypoxia-inducible factor-1α and autophagy-associated proteins, Beclin 1, and LC3
"highlight2" >Hif1a↓,
"highlight2" >LC3II↑, LC3-II is upregulated following the luteolin treatment in p53 wild type HepG2 cells i
"highlight2" >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.

2909- LT,    Revisiting luteolin: An updated review on its anticancer potential
- Review, Var, NA
"highlight2" >Apoptosis↑, inducing apoptosis, initiating cell cycle arrest, and decreasing angiogenesis, metastasis, and cell proliferation, luteolin is used to treat cancer
"highlight2" >TumCCA↑,
"highlight2" >angioG↓,
"highlight2" >TumMeta↓,
"highlight2" >TumCP↓,
"highlight2" >chemoP↑, It exhibits antioxidant properties and can be given to patients receiving Doxorubicin (DOX) chemotherapy to prevent the development of unexpected adverse reactions in the lungs and hematopoietic system subjected to DO
"highlight2" >MDR1↓, Furthermore, it could be an excellent candidate for synergistic studies to overcome drug resistance in cancer cells.

2923- LT,    Luteolin induces apoptosis through endoplasmic reticulum stress and mitochondrial dysfunction in Neuro-2a mouse neuroblastoma cells
- in-vitro, NA, NA
"highlight2" >Apoptosis↑, Luteolin induced apoptotic cell death and activation of caspase-12, -9, and -3
"highlight2" >TumCD↑,
"highlight2" >Casp12↑,
"highlight2" >Casp9↑,
"highlight2" >Casp3↑,
"highlight2" >ER Stress↑, Luteolin also induced expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP) and glucose-regulated proteins (GRP) 94 and 78, cleavage of ATF6α, and phosphorylation of eIF2α
"highlight2" >CHOP↑,
"highlight2" >GRP78/BiP↑,
"highlight2" >GRP94↑,
"highlight2" >cl‑ATF6↑,
"highlight2" >p‑eIF2α↑,
"highlight2" >MMP↓, rapid reduction of mitochondrial membrane potential by luteolin
"highlight2" >JNK↓, luteolin induced activation of mitogen-activated protein kinases such as JNK, p38, and ERK
"highlight2" >p38↑,
"highlight2" >ERK↑,
"highlight2" >Cyt‑c↑, cytochrome c release.

2924- LT,    Luteolin selectively kills STAT3 highly activated gastric cancer cells through enhancing the binding of STAT3 to SHP-1
- in-vitro, GC, NA - in-vivo, NA, NA
"highlight2" >p‑STAT3↓, treatment of luteolin in these GC cells significantly inhibited STAT3 phosphorylation and reduced the expression of STAT3 targeting gene Mcl-1, Survivin and Bcl-xl
"highlight2" >STAT3↓,
"highlight2" >Mcl-1↓,
"highlight2" >survivin↓,
"highlight2" >Bcl-xL↓,
"highlight2" >HSP90↓, t luteolin could bind to HSP-90 directly, and decrease STAT3 phosphorylation

2925- LT,    Luteolin Induces Carcinoma Cell Apoptosis through Binding Hsp90 to Suppress Constitutive Activation of STAT3
- in-vitro, Cerv, HeLa - in-vitro, Nor, HEK293 - in-vitro, BC, MCF-7
"highlight2" >HSP90↓, This study indicated that luteolin may act as a potent HSP90 inhibitor in antitumor strategies.
"highlight2" >p‑STAT3↓, luteolin induced a notable reduction in the level of Tyr705-phosphorylated STAT3,
"highlight2" >Apoptosis↑, Luteolin Induces Apoptosis of Cancer Cells
"highlight2" >selectivity↑, cytotoxicity to cancer cells including HeLa and HepG2, but showed a very slight cytotoxicity to normal cells, such as WRL-68, HEK293 and XJH cells

2926- LT,    Luteolin ameliorates rat myocardial ischemia-reperfusion injury through peroxiredoxin II activation: LUT's cardioprotection through PRX II
- in-vitro, Nor, H9c2
"highlight2" >*cardioP↑, LUT exerted significant cardioprotective effects in vivo and in vitro via improving cardiac function,
"highlight2" >*PrxII↑, Mechanistically, LUT markedly enhanced PRX II expression without significant effects on other PRXs, catalase and SOD1.

2927- LT,    Luteolin Causes 5′CpG Demethylation of the Promoters of TSGs and Modulates the Aberrant Histone Modifications, Restoring the Expression of TSGs in Human Cancer Cells
- in-vitro, Cerv, HeLa
"highlight2" >TumCMig↓, luteolin inhibited migration and colony formation in HeLa cells.
"highlight2" >DNMTs↓, Luteolin decreased DNMT activity in HeLa cells in a concentration-dependent manner.
"highlight2" >HDAC↓, Luteolin Decreases HDAC Activity in HeLa Cells
"highlight2" >HATs↓, Luteolin Reduces the HAT Activity in a Dose-Dependent Manner
"highlight2" >ac‑H3↓, H3 acetylation marks were diminished after treatment with the 20 µM of luteolin
"highlight2" >ac‑H4↓, the acetylation marks at H4 were also modulated,
"highlight2" >MMP2↓, Luteolin resulted in downregulation of expression of various proteins related to migration and inflammation in HeLa cells, and fold changes (FC) after treatment with 10 and 20 µM for 48 h are given, respectively, for MMP2 (FC 0.33, 0.26), MMP3 (FC 0.
"highlight2" >MMP9↓,
"highlight2" >HO-1↓, Genes related to cell proliferation, growth, and apoptosis such as BCL-X (FC 0.55, 0.45), HO-1/HMOX1 (FC 0.40, 0.25), Kallikrein6 (FC 0.55, 0.48), Kallikrein 3/PSA (FC 0.58, 0.48) were reduced.
"highlight2" >E-cadherin↑, E-cadherin (FC 1.8, 2.9) were upregulated
"highlight2" >EZH2↓, Luteolin has depicted increased expression of MiR-26a, which is a regulator of EZH2, and at the same time, it has inhibited EZH2
"highlight2" >HER2/EBBR2↓, luteolin treatment decreased the inflammatory and migratory proteins such as MMp-2, MMP-3, HO-1/HMOX1, Her1, HER2, Her4, mesothelin, cathepsin B, MUC1, nectin 4, FOXC2, IL-18 BPa, CCL3/MIP-1α, CXCL8/IL-8, IL-2
"highlight2" >IL18↓,
"highlight2" >IL8↓,
"highlight2" >IL2↓,

2928- LT,    Luteolin-mediated increase in miR-26a inhibits prostate cancer cell growth and induces cell cycle arrest targeting EZH2
"highlight2" >EZH2↓, Human prostate cancer DU145 and PC-3 cells, which possess high constitutive EZH2 expression, were treated with 5-20 µM luteolin at various times significantly inhibited EZH2
"highlight2" >cycD1↓, Mechanistic investigations revealed that miR-26a overexpression suppressed cell cycle regulatory molecules such as cyclin D and E, cyclin dependent kinases CDK4 and CDK6
"highlight2" >cycE↓,
"highlight2" >CDK4↓,
"highlight2" >CDK6↓,

2929- LT,    Loss of BRCA1 in the cells of origin of ovarian cancer induces glycolysis: A window of opportunity for ovarian cancer chemoprevention
- in-vitro, Ovarian, NA
"highlight2" >HK2↓, . Figure 5b Aspirin and luteolin suppress HK2 and glycolysis in IOSE and FT cells.
"highlight2" >Myc↓, Two agents, aspirin and luteolin, induced a dose-dependent decrease in the protein levels of HK2 and reduced MYC expression
"highlight2" >Glycolysis↓,

2930- LT,    Luteolin confers renoprotection against ischemia–reperfusion injury via involving Nrf2 pathway and regulating miR320
- in-vitro, Nor, NA
"highlight2" >*RenoP↑, luteolin protects the kidney against I/R injury via reducing oxidative stress, increasing antioxidant enzymes and reducing expression of Nrf2 and miR320.
"highlight2" >*ROS↓,
"highlight2" >*antiOx↑,
"highlight2" >*NRF2↓, luteolin protects the kidney against I/R injury via reducing oxidative stress, increasing antioxidant enzymes and reducing expression of Nrf2 and miR320.

4292- LT,    Luteolin for neurodegenerative diseases: a review
- Review, AD, NA - Review, Park, NA - Review, MS, NA - Review, Stroke, NA
"highlight2" >*Inflam↓, luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity.
"highlight2" >*antiOx↑,
"highlight2" >*neuroP↑,
"highlight2" >*BioAv↝, To increase the bioavailability of luteolin, several delivery methods have been developed; the most thoroughly studied include lipid carriers like liposomes and nanoformulations
"highlight2" >*BBB↑, luteolin given intraperitoneally (ip) to mice can readily cross the blood-brain barrier (BBB) and enter the brain
"highlight2" >*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
"highlight2" >*IL1β↓,
"highlight2" >*IL6↓,
"highlight2" >*IL8↓,
"highlight2" >*IL33↓,
"highlight2" >*NF-kB↓, inhibition of the NF-кB pathway
"highlight2" >*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
"highlight2" >*ROS↓, anti-oxidant activity mainly by reducing ROS levels and increasing SOD activity in in vitro models of AD
"highlight2" >*SOD↑,
"highlight2" >*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
"highlight2" >*NRF2↑,
"highlight2" >*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
"highlight2" >*Casp9↑,
"highlight2" >*Bax:Bcl2↓,
"highlight2" >*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.
"highlight2" >*GRP78/BiP↑,
"highlight2" >*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
"highlight2" >*GSK‐3β↓, inactivating the glycogen synthase kinase-3 alpha (GSK-3α) isoform, suppressing Aβ and promoting tau disaggregation
"highlight2" >*tau↓,
"highlight2" >*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
"highlight2" >*ATP↑, ROS production was decreased by 40%, MMP levels were restored close to control N2a levels (202%), and ATP levels were improved by 444%).
"highlight2" >*cognitive↑, protective effect of luteolin against cognitive dysfunction was also reported in the streptozotocin
"highlight2" >*BloodF↑, Luteolin increased regional cerebral blood flow values, alleviated the leakage of the lumen of vessels, and protected the integrity of BBB
"highlight2" >*BDNF↑, increasing the level of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor (TrkB) expression in the cerebral cortex
"highlight2" >*TrkB↑,
"highlight2" >*memory↑, luteolin supplementation significantly ameliorated memory and cognitive deficits in 3 × Tg-AD mice.
"highlight2" >*PPARγ↑, attenuated mitochondrial dysfunction via peroxisome proliferator-activated receptor gamma (PPARγ) activation.
"highlight2" >*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
"highlight2" >*Inflam↓, luteolin, a natural flavonoid compound with anti-inflammatory, antioxidant, and neuroprotective properties.
"highlight2" >*antiOx↑,
"highlight2" >*neuroP↑,
"highlight2" >*cognitive↑, results indicated that treatment with luteolin improved the degree of cognitive impairment in mice with DE.
"highlight2" >*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
"highlight2" >*p‑NF-kB↓,
"highlight2" >*HDAC2↓,
"highlight2" >*BDNF↑,
"highlight2" >*other↓, luteolin may also directly target HDAC2, as an HDAC2 inhibitor, to alleviate DE, complementing mTOR/NF-κB signaling inhibition
"highlight2" >*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

4294- LT,    Luteolin reduces zinc-induced tau phosphorylation at Ser262/356 in an ROS-dependent manner in SH-SY5Y cells
- in-vitro, NA, SH-SY5Y
"highlight2" >*tau↓, Lu efficiently attenuates zinc-induced tau hyperphosphorylation through not only its antioxidant action but also its regulation of the phosphorylation/dephosphorylation system
"highlight2" >*antiOx↑,

4295- LT,    Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury
- in-vivo, AD, NA
"highlight2" >*Aβ↓, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolis
"highlight2" >*GSK‐3β↓,
"highlight2" >*p‑tau↓,
"highlight2" >*BBB↑, we determined the ability of peripherally administered luteolin to cross the blood brain barrier (BBB).

4338- LT,    Luteolin: a natural product with multiple mechanisms for atherosclerosis
- Review, NA, NA
"highlight2" >*Inflam↓, Figure 2
"highlight2" >*ROS↓,
"highlight2" >*PDGF↓, luteolin 7-glucoside (L7G) can inhibit PDGF-BB-induced VSMC proliferation and DNA synthesis by blocking the phosphorylation of PLC-γ1, Akt, and Erk1/2, ultimately inhibiting VSMC proliferation.
"highlight2" >*lipid-P↓, luteolin prevents aortic lipid accumulation and atherosclerotic plaque formation in LDLR −/− mice induced by a Western diet.
"highlight2" >*AMPK↑, luteolin prevents aortic lipid accumulation and atherosclerotic plaque formation in LDLR −/− mice induced by a Western diet.
"highlight2" >*SIRT1↑,
"highlight2" >*AntiAg↑,

4339- LT,    Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis
- in-vivo, NA, NA
"highlight2" >*AntiAg↑, Luteolin inhibits platelet activation and thrombus formation
"highlight2" >*ROS↓, Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity.

1534- LT,  Api,  EGCG,  RES,    Plant polyphenol induced cell death in human cancer cells involves mobilization of intracellular copper ions and reactive oxygen species generation: a mechanism for cancer chemopreventive action
- in-vitro, Nor, MCF10 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468 - in-vitro, PC, Bxpc-3
"highlight2" >TumCP↓,
"highlight2" >Apoptosis↑,
"highlight2" >eff↓, cell death is prevented to a significant extent by cuprous chelator neocuproine and reactive oxygen species scavengers
"highlight2" >*toxicity↑, normal breast epithelial cells, cultured in a medium supplemented with copper, become sensitized to polyphenol-induced growth inhibition.
"highlight2" >Dose?, apigenin at 5uM promoted growth in MCF10A cells and PC3 cancer cells. This could be because polyphenols at lower concentrations are known to be associated with cell proliferation [21], while behaving as prooxidants at high concentrations
"highlight2" >eff↓, Apigenin- and luteolin-induced antiproliferation and apoptosis in cancer cells is inhibited by cuprous chelator but not by iron and zinc chelators
"highlight2" >eff↓, EGCG and resveratrol, similar to that of the flavones luteolin and apigenin, also involves the mobilization of endogenous copper and consequent prooxidant effect leading to cell death.

979- LT,    Luteolin Regulation of Estrogen Signaling and Cell Cycle Pathway Genes in MCF-7 Human Breast Cancer Cells
- in-vitro, BC, MCF-7
"highlight2" >TumCP↓, Luteolin inhibits the proliferation of our ER(+) MCF-7 cells (Figure 1) which contain ERα (but not ERβ)

982- LT,    Inhibitory effect of luteolin on estrogen biosynthesis in human ovarian granulosa cells by suppression of aromatase (CYP19)
- in-vitro, Ovarian, KGN
"highlight2" >CYP19↓, aromatase inhibitor

986- LT,  doxoR,    Luteolin as a glycolysis inhibitor offers superior efficacy and lesser toxicity of doxorubicin in breast cancer cells
- in-vitro, BC, 4T1 - in-vitro, BC, MCF-7
"highlight2" >SOD↓, the activity of SOD and CAT was increased in serum and was decreased in tumor by Lu in vivo
"highlight2" >Catalase↓,
"highlight2" >Glycolysis↓, glycolytic inhibitor

1025- LT,  Api,    Luteolin and its derivative apigenin suppress the inducible PD-L1 expression to improve anti-tumor immunity in KRAS-mutant lung cancer
- in-vivo, Lung, NA
"highlight2" >TumCG↓,
"highlight2" >Apoptosis↑,
"highlight2" >PD-L1↓, down-regulated the IFN-γ-induced PD-L1 expression
"highlight2" >p‑STAT3↓,

1060- LT,  BTZ,    Luteolin inhibits the TGF-β signaling pathway to overcome bortezomib resistance in multiple myeloma
- vitro+vivo, Melanoma, NA
"highlight2" >ALDH1A1↓, decreasing the proportion of ALDH1+ cells
"highlight2" >TGF-β↓,
"highlight2" >ChemoSen↑, combination of LUT and BTZ had a synergistic effect against myeloma cells.

1064- LT,  Cisplatin,    Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells
- vitro+vivo, Lung, LNM35 - in-vitro, CRC, HT-29 - in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
"highlight2" >Casp3↑,
"highlight2" >Casp7↑,
"highlight2" >HDAC↓, luteolin is a potent HDAC inhibitor

1084- LT,  CHr,    Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells
- in-vitro, Nor, RAW264.7
"highlight2" >*COX2↓, 25, 50, or 100 micromol/L concentrations of luteolin inhibited (lipopolysaccharide (LPS)-induced) Cox-2 protein expression
"highlight2" >*COX2∅, Chrysin pretreatment did not reduce (LPS-induced) Cox-2 protein expression at any level tested.
"highlight2" >*PGE2↓, both luteolin and chrysin completely suppressed (LPS-induced) PGE2 formation
"highlight2" >*ROS↓, only Luteolin suppressed superoxide formation (induced by xanthine)

1100- LT,    Luteolin, a flavonoid, as an anticancer agent: A review
- Review, NA, NA
"highlight2" >TumCP↓,
"highlight2" >TumCCA↑,
"highlight2" >Apoptosis↑,
"highlight2" >EMT↓, reverse epithelial-mesenchymal transition (EMT)
"highlight2" >E-cadherin↑,
"highlight2" >N-cadherin↓,
"highlight2" >Snail↓,
"highlight2" >Vim↓,
"highlight2" >ROS↑, Luteolin increases levels of intracellular reactive oxygen species (ROS) by activation
"highlight2" >ER Stress↑,
"highlight2" >mtDam↑, mitochondrial dysfunction
"highlight2" >p‑eIF2α↝,
"highlight2" >p‑PERK↝,
"highlight2" >p‑CHOP↝,
"highlight2" >p‑ATF4↝,
"highlight2" >cl‑Casp12↝,

1125- LT,    Luteolin suppresses epithelial-mesenchymal transition and migration of triple-negative breast cancer cells by inhibiting YAP/TAZ activity
- in-vitro, BC, NA
"highlight2" >YAP/TEAD↓,
"highlight2" >TAZ↓,
"highlight2" >MSCmark↓,
"highlight2" >EM↑,
"highlight2" >TumCMig↓,

1171- LT,    The inhibition of β-catenin activity by luteolin isolated from Paulownia flowers leads to growth arrest and apoptosis in cholangiocarcinoma
- in-vitro, CCA, NA
"highlight2" >Wnt↓,
"highlight2" >TumCCA↑, G2/M phase
"highlight2" >Apoptosis↑,
"highlight2" >TumCMig↓,
"highlight2" >β-catenin/ZEB1↓, inhibitor of β-catenin
"highlight2" >cMyc↓,
"highlight2" >cycD1↓,

1200- LT,    Inhibition of Fatty Acid Synthase by Luteolin Post-Transcriptionally Downregulates c-Met Expression Independent of Proteosomal/Lysosomal Degradation
- in-vitro, Pca, DU145
"highlight2" >FASN↓, luteolin, a potent FASN inhibitor
"highlight2" >cMET↓,
"highlight2" >HGF/c-Met↓,

1275- LT,    Mechanism of luteolin induces ferroptosis in nasopharyngeal carcinoma cells
- in-vitro, Laryn, NA
"highlight2" >Ferroptosis↑,
"highlight2" >MDA↑,
"highlight2" >Iron↑,
"highlight2" >SOD↓,
"highlight2" >GSH↓,
"highlight2" >GPx4↓,
"highlight2" >SOX4↓,
"highlight2" >GDF15↓,

1317- LT,    Luteolin Suppresses Teratoma Cell Growth and Induces Cell Apoptosis via Inhibiting Bcl-2
- vitro+vivo, Ovarian, PA1
"highlight2" >Bcl-2↓,
"highlight2" >BAX↑,
"highlight2" >Apoptosis↑,
"highlight2" >TumCG↓,

2910- LT,  FA,    Folic acid-modified ROS-responsive nanoparticles encapsulating luteolin for targeted breast cancer treatment
- in-vitro, BC, 4T1 - in-vivo, NA, NA
"highlight2" >BioAv↓, poor aqueous solubility and low bioactivity of Lut restrict its clinical translation
"highlight2" >BioAv↑, Herein, we developed a reactive oxygen species (ROS)-responsive nanoplatforms to improve the bioactivity of Lut.
"highlight2" >eff↑, inhibited tumor growth ∼3 times compared to the Lut group
"highlight2" >tumCV↓, viability of 4T1 cells was decreased significantly when treated with upon 40 µM of Lut/FA-Oxi-αCD NPs
"highlight2" >e-H2O2↓, Interestingly, the extracellular H2O2 concentration of 4T1 cells was decreased obviously with Lut treatment, due to Lut is a widely used antioxidant that can eliminate ROS
"highlight2" >i-H2O2∅, However, both Lut and blank Oxi-αCD NPs could not eliminate intracellular H2O2

2346- LT,    Luteolin suppressed PKM2 and promoted autophagy for inducing the apoptosis of hepatocellular carcinoma cells
- in-vitro, HCC, HepG2
"highlight2" >TumCP↓, luteolin could suppress the proliferation of hepatic carcinoma cells and promote cellular apoptosis in a concentration-dependent manner;
"highlight2" >Apoptosis↓,
"highlight2" >PKM2↓, luteolin could suppress the expression of PKM2 and knock down PKM2.With a rising concentration of luteolin, the expression of PKM2 gradually declined
"highlight2" >TumAuto↑, Luteolin promotes autophagy through suppressing the expression of PKM2 and promoting apoptosis of hepatic carcinoma cells.

2587- LT,    Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs
- in-vitro, Lung, A549
"highlight2" >NRF2↓, luteolin elicited a dramatic reduction in Nrf2 at both the mRNA and the protein levels, leading to decreased Nrf2 binding to AREs, down-regulation of ARE-driven genes, and depletion of reduced glutathione.
"highlight2" >GSH↓,
"highlight2" >ChemoSen↑, luteolin significantly sensitized A549 cells to the anticancer drugs oxaliplatin, bleomycin, and doxorubicin.
"highlight2" >HO-1↓, ↓HO-1

2588- LT,  Chemo,    Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway
- in-vitro, CRC, HCT116
"highlight2" >NRF2↓, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner.
"highlight2" >NQO1↓, Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and GSTα1/2] expression and decreased reduced glutathione in wild type mouse small intestinal cells.
"highlight2" >HO-1↓,
"highlight2" >GSH↓,
"highlight2" >ChemoSen↑, uteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect.

2589- LT,  Chemo,    Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway
- in-vitro, BC, MDA-MB-231
"highlight2" >NRF2↓, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features
"highlight2" >HO-1↓,
"highlight2" >ChemoSen↑, combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells.
"highlight2" >CSCs↓, Luteolin Inhibited Cancer Stemness Capacity in MDA-MB-231 Cells
"highlight2" >SIRT1↓, luteolin suppressed Nrf2, HO-1, Sirt3, and Cripto-1 expression in MDA-MB-231 cells.

2595- LT,    Regulation of Nrf2/ARE Pathway by Dietary Flavonoids: A Friend or Foe for Cancer Management?
- Review, Var, NA
"highlight2" >*NRF2↑, Nrf2/ARE Activation in Non-Cancer Experimental Model - (luteolin, baicalin and apigenin) are more prominent in upregulating Nrf2 protein expression in both in vitro
"highlight2" >NRF2↓, , luteolin, apigenin and chrysin, were found to be effective in inhibiting the Nrf2/ARE pathway in different cancer cell lines [60,61,62,63,68,209].
"highlight2" >NRF2⇅, luteolin exhibits dual roles in cancer cell growth in vitro and cancer promotion in vivo

2903- LT,    Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG - in-vivo, NA, NA
"highlight2" >ER Stress↑, Luteolin induced a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in glioblastoma cells by increasing intracellular reactive oxygen species (ROS) levels.
"highlight2" >ROS↑,
"highlight2" >PERK↑, Luteolin induced expression of ER stress-associated proteins, including phosphorylation of PERK, eIF2α, ATF4, CHOP and cleaved-caspase 12.
"highlight2" >eIF2α↑,
"highlight2" >ATF4↑,
"highlight2" >CHOP↑,
"highlight2" >Casp12↑,
"highlight2" >eff↓, Inhibition of ROS production by anti-oxidant N-acetylcysteine could reverse luteolin-induced ER stress and mitochondrial pathways activation as well as apoptosis.
"highlight2" >UPR↑, Researches indicate that abnormalities in ER function can cause ER stress, resulting in unfolded protein response (UPR),
"highlight2" >MMP↓, integrity of mitochondrial membranes potential decreased in U87MG cells after treatment of 40 uM luteolin
"highlight2" >Cyt‑c↑, release of cytochrome C to cytoplasm was elevated in U251MG cells
"highlight2" >Bcl-2↓, significantly decreased the expression of anti-apoptotic protein Bcl-2 and increased the expression of pro-apoptotic protein Bax in U251MG and U87MG glioblastoms cells.
"highlight2" >BAX↑,
"highlight2" >TumCG↓, Luteolin inhibited tumor growth in a xenograft mouse model
"highlight2" >Weight∅, luteolin did not affect body weight, alanine aminotransferase (ALT) or aspartate transaminase (AST)
"highlight2" >ALAT∅,
"highlight2" >AST∅,

2904- LT,    Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons
- in-vitro, Park, SK-N-SH - in-vitro, AD, NA
"highlight2" >*ROS↓, Food-derived compound luteolin possesses multitarget actions including reactive oxygen species (ROS)-scavenging activit
"highlight2" >*neuroP↑, Upon the ROS-insulted primary neurons, luteolin concentration-dependently enhanced neuronal cell survival with efficacy higher than and potency similar to vitamin E.
"highlight2" >*MMP↑, prevented the decreases in activities of mitochondria, catalase, and glutathione in ROS-insulted primary neurons
"highlight2" >*Catalase↑, decreases of catalase/glutathione activity by H 2O 2 were markedly reversed following luteolin treatment.
"highlight2" >*GSH↑,
"highlight2" >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
"highlight2" >*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
"highlight2" >*Cyt‑c↓, reduction of cytochrome c release from mitochondria into cytosome,

2905- LT,    Luteolin blocks the ROS/PI3K/AKT pathway to inhibit mesothelial-mesenchymal transition and reduce abdominal adhesions
- in-vivo, NA, HMrSV5
"highlight2" >*ROS↓, It attenuated H2O2-induced ROS production and reversed mesothelial-mesenchymal transition (MMT) in HMrSV5 cells.
"highlight2" >*p‑Akt↓, Phosphorylated Akt levels were significantly reduced in LUT-treated HMrSV5 cells
"highlight2" >*Vim↓, LUT also significantly reduced the expression of vimentin and collagen I in adherent tissues and upregulated E-cadherin expression
"highlight2" >*E-cadherin↑,
"highlight2" >*PI3K↓, LUT blocks the ROS/PI3K/AKT pathway, thereby inhibiting MMT and reducing PAA.

2906- LT,    Luteolin, a flavonoid with potentials for cancer prevention and therapy
- Review, Var, NA
"highlight2" >*Inflam↓, anti-inflammation, anti-allergy and anticancer, luteolin functions as either an antioxidant or a pro-oxidant biochemically
"highlight2" >AntiCan↑,
"highlight2" >antiOx⇅, With low Fe ion concentrations (< 50 μM), luteolin behaves as an antioxidant while high Fe concentrations (>100 μM) induce luteolin's pro-oxidative effect
"highlight2" >Apoptosis↑, induction of apoptosis, and inhibition of cell proliferation, metastasis and angiogenesis.
"highlight2" >TumCP↓,
"highlight2" >TumMeta↓,
"highlight2" >angioG↓,
"highlight2" >PI3K↓, , luteolin sensitizes cancer cells to therapeutic-induced cytotoxicity through suppressing cell survival pathways such as phosphatidylinositol 3′-kinase (PI3K)/Akt, nuclear factor kappa B (NF-κB), and X-linked inhibitor of apoptosis protein (XIAP)
"highlight2" >Akt↓,
"highlight2" >NF-kB↓,
"highlight2" >XIAP↓, luteolin inhibits PKC activity, which results in a decrease in the protein level of XIAP by ubiquitination and proteasomal degradation of this anti-apoptotic protein
"highlight2" >P53↑, stimulating apoptosis pathways including those that induce the tumor suppressor p53
"highlight2" >*ROS↓, Direct evidence showing luteolin as a ROS scavenger was obtained in cell-free systems
"highlight2" >*GSTA1↑, Third, luteolin may exert its antioxidant effect by protecting or enhancing endogenous antioxidants such as glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT)
"highlight2" >*GSR↑,
"highlight2" >*SOD↑,
"highlight2" >*Catalase↑,
"highlight2" >*other↓, luteolin may chelate transition metal ions responsible for the generation of ROS and therefore inhibit lipooxygenase reaction, or suppress nontransition metal-dependent oxidation
"highlight2" >ROS↑, Luteolin has been shown to induce ROS in untransformed and cancer cells
"highlight2" >Dose↝, It is believed that flavonoids could behave as antioxidants or pro-oxidants, depending on the concentration and the source of the free radicals
"highlight2" >chemoP↑, may act as a chemopreventive agent to protect cells from various forms of oxidant stresses and thus prevent cancer development
"highlight2" >NF-kB↓, We found that luteolin-induced oxidative stress causes suppression of the NF-κB pathway while it triggers JNK activation, which potentiates TNF-induced cytotoxicity in lung cancer cells
"highlight2" >JNK↑,
"highlight2" >p27↑, Table 1
"highlight2" >P21↑,
"highlight2" >DR5↑,
"highlight2" >Casp↑,
"highlight2" >Fas↑,
"highlight2" >BAX↑,
"highlight2" >MAPK↓,
"highlight2" >CDK2↓,
"highlight2" >IGF-1↓,
"highlight2" >PDGF↓,
"highlight2" >EGFR↓,
"highlight2" >PKCδ↓,
"highlight2" >TOP1↓,
"highlight2" >TOP2↓,
"highlight2" >Bcl-xL↓,
"highlight2" >FASN↓,
"highlight2" >VEGF↓,
"highlight2" >VEGFR2↓,
"highlight2" >MMP9↓,
"highlight2" >Hif1a↓,
"highlight2" >FAK↓,
"highlight2" >MMP1↓,
"highlight2" >Twist↓,
"highlight2" >ERK↓,
"highlight2" >P450↓, Recently, it was determined that luteolin potently inhibits human cytochrome P450 (CYP) 1 family enzymes such as CYP1A1, CYP1A2, and CYP1B1, thereby suppressing the mutagenic activation of carcinogens
"highlight2" >CYP1A1↓,
"highlight2" >CYP1A2↓,
"highlight2" >TumCCA↑, Luteolin is able to arrest the cell cycle during the G1 phase in human gastric and prostate cancer, and in melanoma cells

2907- LT,    Protective effect of luteolin against oxidative stress‑mediated cell injury via enhancing antioxidant systems
- in-vitro, Nor, NA
"highlight2" >*ROS↓, Intracellular ROS levels and damage to cellular components such as lipids and DNA in H2O2-treated cells were significantly decreased by luteolin pretreatment.
"highlight2" >*Casp9↓, Luteolin suppressed active caspase-9 and caspase-3 levels while increasing Bcl-2 expression and decreasing Bax protein levels.
"highlight2" >*Casp3↓,
"highlight2" >*Bcl-2↑,
"highlight2" >*BAX↓,
"highlight2" >*GSH↑, luteolin restored levels of glutathione that was reduced in response to H2O2.
"highlight2" >*SOD↑, luteolin enhanced the activity and protein expressions of superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1.
"highlight2" >*Catalase↑,
"highlight2" >*GPx↑,
"highlight2" >*HO-1↑,
"highlight2" >*antiOx↑, upregulating antioxidant enzymes.
"highlight2" >*lipid-P↓, protective effect of luteolin against lipid peroxidation
"highlight2" >*p‑γH2AX↓, showed that luteolin pretreatment diminished expression levels of phospho-H2A.X in H2O2-exposed cells
"highlight2" >eff↑, promising therapeutic agent for management and treatment of conditions such as COPD and pulmonary fibrosis.

2908- LT,    Luteolin attenuates neutrophilic oxidative stress and inflammatory arthritis by inhibiting Raf1 activity
- in-vitro, Arthritis, NA
"highlight2" >*ROS↓, Luteolin significantly inhibited superoxide anion generation, ROS production, and NET formation in human neutrophils.
"highlight2" >*p‑ERK↓, Luteolin significantly suppressed phosphorylation of extracellular signal-regulated kinase (Erk) and mitogen-activated protein kinase kinase-1 (MEK-1)
"highlight2" >*p‑MEK↓,
"highlight2" >*Raf↓, luteolin acts as a Raf-1 inhibitor

973- LT,    Luteolin impairs hypoxia adaptation and progression in human breast and colon cancer cells
- in-vitro, CRC, HCT116 - in-vitro, BC, MDA-MB-231
"highlight2" >Apoptosis↑,
"highlight2" >necrosis↑,
"highlight2" >TumAuto↑,
"highlight2" >HIF-1↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 58

Results for Effect on Cancer/Diseased Cells:
AEG1↓,1,   AIF↑,1,   Akt↓,3,   Akt↑,1,   p‑Akt↓,2,   AKT1↓,2,   Akt2↓,1,   ALAT∅,1,   ALDH1A1↓,1,   angioG↓,4,   AntiCan↑,1,   antiOx⇅,1,   APAF1↑,1,   Apoptosis↓,1,   Apoptosis↑,12,   AR↓,2,   ASC↓,1,   AST∅,1,   ATF2↓,1,   ATF4↑,2,   p‑ATF4↝,1,   cl‑ATF6↑,1,   ATP↓,1,   AXL↓,1,   BAD↑,1,   BAX↑,8,   Bax:Bcl2↑,1,   Bcl-2↓,8,   Bcl-xL↓,2,   Beclin-1↑,3,   BID↑,1,   BioAv↓,1,   BioAv↑,3,   BNIP3↑,1,   BOK↑,1,   Ca+2↑,2,   cachexia↓,1,   cardioP↑,1,   Casp↑,1,   Casp1↓,1,   Casp12↑,2,   cl‑Casp12↑,1,   cl‑Casp12↝,1,   Casp3↑,7,   cl‑Casp3↑,1,   Casp7↑,1,   Casp8↑,3,   cl‑Casp8↑,1,   Casp9↑,5,   cl‑Casp9↑,1,   proCasp9↓,1,   Catalase↓,3,   Catalase↑,1,   CD34↓,1,   CDC2↓,2,   Cdc42↓,1,   CDK2↓,5,   CDK4↓,2,   CDK6↓,1,   CEA↓,1,   cFos↑,1,   chemoP↑,4,   ChemoSen↓,1,   ChemoSen↑,7,   CHOP↑,3,   p‑CHOP↝,1,   CLDN1↓,1,   cMET↓,1,   cMyc↓,3,   p‑cMyc↑,1,   COX2↓,1,   CSCs↓,1,   CXCR4↓,1,   cycA1↑,1,   CycB↓,2,   cycD1↓,3,   cycE↓,1,   CYP19↓,1,   CYP1A1↓,2,   CYP1A2↓,1,   Cyt‑c↑,5,   DNAdam↑,1,   DNMT1↓,1,   DNMT3A↓,1,   DNMTs↓,2,   Dose?,1,   Dose↝,1,   DR5↑,5,   E-cadherin↓,1,   E-cadherin↑,5,   ECM/TCF↓,1,   eff↓,4,   eff↑,4,   EGFR↓,1,   EGFR↑,1,   p‑EGFR↓,1,   eIF2α↑,2,   p‑eIF2α↑,2,   p‑eIF2α↝,1,   EM↑,1,   EMT↓,5,   ER Stress↑,5,   ERK↓,2,   ERK↑,1,   p‑ERK↓,2,   EZH2↓,2,   FADD↑,1,   FAK↓,3,   Fas↑,4,   FasL↑,1,   FASN↓,2,   Ferroptosis↑,1,   GDF15↓,1,   Glycolysis↓,2,   GPx↓,1,   GPx4↓,1,   GRP78/BiP↑,1,   GRP94↑,1,   GSH↓,5,   GSK‐3β↓,1,   p‑GSK‐3β↓,1,   GSR↓,1,   GSS↑,1,   GSTs↓,2,   GutMicro↑,1,   e-H2O2↓,1,   i-H2O2∅,1,   H3↓,1,   ac‑H3↓,1,   H4↓,1,   ac‑H4↓,1,   Half-Life↝,1,   HATs↓,1,   HDAC↓,4,   HER2/EBBR2↓,1,   HGF/c-Met↓,2,   HIF-1↓,1,   Hif1a↓,2,   HK2↓,1,   HO-1↓,6,   HO-1↑,1,   HSP90↓,2,   hTERT↓,3,   ICAM-1↓,1,   IFN-γ↓,1,   IGF-1↓,1,   IKKα↓,1,   IL1↓,1,   IL18↓,1,   IL2↓,1,   IL2↑,1,   IL6↓,2,   IL8↓,1,   iNOS↓,1,   Iron↑,1,   IronCh↑,1,   ITGB1↓,1,   JNK↓,1,   JNK↑,2,   p‑JNK↑,1,   LC3B-II↑,1,   LC3II↑,2,   MAPK↓,3,   MAPK↑,1,   Mcl-1↓,2,   MDA↑,1,   MDM2↓,2,   p‑MDM2↓,1,   MDR1↓,2,   p‑MEK↓,1,   MET↓,1,   p‑MET↓,1,   MMP↓,5,   MMP1↓,1,   MMP2↓,4,   MMP9↓,4,   MSCmark↓,1,   mtDam↑,2,   mTOR↓,1,   Myc↓,1,   N-cadherin↓,5,   NAIP↓,1,   necrosis↑,1,   NF-kB↓,8,   p‑NF-kB↑,1,   NICD↓,1,   NLRP3↓,1,   NOTCH↓,1,   NOTCH1↓,2,   NQO1↓,2,   NRF2↓,8,   NRF2↑,2,   NRF2⇅,1,   NSE↓,1,   P21↑,3,   p27↑,1,   p38↑,1,   p‑p38↑,2,   P450↓,1,   P53↑,4,   p‑p65↓,1,   PARP↑,1,   cl‑PARP↑,1,   PCNA↓,1,   PD-1↓,1,   PD-L1↓,1,   PDGF↓,1,   PERK↑,2,   p‑PERK↝,1,   PI3K↓,4,   p‑PI3K↓,1,   PKCδ↓,1,   PKM2↓,1,   PTEN↓,1,   Rac1↓,1,   RadioS↑,3,   RAS↓,1,   Rho↓,1,   ROS↓,2,   ROS↑,11,   selectivity↑,2,   SIRT1↓,2,   Snail↓,3,   SOD↓,6,   SOD2↓,1,   SOX4↓,1,   p‑Src↓,1,   SREBP2↓,1,   STAT3↓,3,   p‑STAT3↓,4,   p‑STAT6↓,1,   survivin↓,2,   TAZ↓,2,   Telomerase↓,2,   TET1↑,2,   TET2↓,1,   TET3↑,1,   TGF-β↓,1,   TIMP1↑,1,   TIMP2↑,1,   TNF-α↓,2,   TOP1↓,1,   TOP2↓,1,   Trx1↑,1,   TrxR1↓,1,   TumAuto↑,3,   TumCCA↑,8,   TumCD↑,1,   TumCG↓,4,   TumCMig↓,3,   TumCP↓,9,   tumCV↓,2,   TumMeta↓,2,   Twist↓,2,   Tyro3↓,1,   UPR↑,1,   VEGF↓,4,   VEGFR2↓,2,   Vim↓,3,   Vim↑,1,   VitC↓,1,   VitE↓,1,   Weight∅,1,   Wnt↓,2,   XIAP↓,4,   YAP/TEAD↓,2,   ZO-1↑,1,   β-catenin/ZEB1↓,2,  
Total Targets: 268

Results for Effect on Normal Cells:
AChE↓,3,   ACSL4∅,1,   p‑Akt↓,1,   ALAT↓,1,   AMPK↑,2,   AntiAg↑,2,   antiOx↑,8,   AP-1↓,1,   AST↓,1,   ATF4↓,1,   ATP↑,1,   Aβ↓,3,   BACE↓,1,   BAX↓,1,   Bax:Bcl2↓,1,   BBB↑,3,   Bcl-2↑,1,   BDNF↑,2,   Beclin-1↓,1,   BioAv↓,3,   BioAv↑,1,   BioAv↝,1,   BloodF↑,1,   cardioP↑,1,   Casp1↓,1,   Casp3↓,3,   Casp9↓,1,   Casp9↑,1,   Catalase↑,5,   CHOP↓,1,   cognitive↑,2,   COX2↓,2,   COX2∅,1,   CREB↑,1,   Cyt‑c↓,1,   E-cadherin↑,1,   eff↑,4,   ER Stress↓,1,   p‑ERK↓,1,   Ferroptosis↓,1,   GPx↑,2,   GPx4∅,1,   GRP78/BiP↑,1,   GSH↑,5,   GSK‐3β↓,2,   GSR↑,2,   GSTA1↑,1,   GSTs↑,2,   GutMicro↑,1,   Half-Life↝,1,   HDAC2↓,1,   hepatoP↑,1,   HO-1↑,3,   HO-1∅,1,   IFN-γ↓,1,   IL10↑,1,   IL18↓,1,   IL1β↓,3,   IL2↓,1,   IL33↓,1,   IL6↓,3,   IL8↓,1,   Inflam↓,5,   iNOS↓,1,   IronCh↑,1,   p‑JNK↓,1,   LDHA↑,1,   lipid-P↓,5,   MDA↓,2,   p‑MEK↓,1,   memory↑,1,   p‑MKK4↑,1,   MMP↑,2,   MMP1↓,1,   p‑mTOR↓,1,   neuroP↑,5,   NF-kB↓,2,   p‑NF-kB↓,1,   NLRP3↓,1,   NO↓,1,   NQO1↑,1,   NRF2↓,1,   NRF2↑,4,   NRF2∅,1,   other↓,2,   p‑p38↓,1,   PDGF↓,1,   PGE2↓,1,   PI3K↓,1,   PPARα↑,1,   PPARγ↑,1,   PrxII↑,1,   Raf↓,1,   RenoP↑,1,   ROS↓,15,   SIRT1↑,2,   SOD↑,7,   SREBP1↓,1,   tau↓,2,   p‑tau↓,2,   TLR4↓,1,   TNF-α↓,2,   toxicity↓,1,   toxicity↑,1,   TrkB↑,1,   TXNIP↓,1,   UPR↑,1,   Vim↓,1,   ZO-1↑,1,   p‑γH2AX↓,1,  
Total Targets: 110

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:118  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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