Luteolin / NF-kB Cancer Research Results

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.

Luteolin — a naturally occurring polyhydroxylated flavone (3′,4′,5,7-tetrahydroxyflavone) found in celery, parsley, peppers, broccoli and numerous medicinal plants. It is a dietary phytochemical and experimental small-molecule anticancer/anti-inflammatory agent rather than an approved anticancer drug. Standard abbreviation: LUT or Lut. Luteolin occurs as the free aglycone and as plant glycosides; after oral administration, circulating luteolin is dominated by glucuronide and sulfate conjugates rather than free aglycone. Its cancer pharmacology is pleiotropic and strongly model-dependent, with particularly recurrent effects on PI3K/AKT/mTOR, NF-κB, STAT3, redox regulation, mitochondrial apoptosis, EMT/invasion and cell-cycle control.

Primary mechanisms (ranked):

  1. PI3K/AKT/mTOR survival signaling suppression, reducing proliferation and facilitating apoptosis, autophagy or other programmed cell-death responses.
  2. Redox-selective stress modulation: commonly ↑ ROS in susceptible cancer cells together with ↓ NRF2/HO-1/GSH-associated antioxidant defenses, while frequently reducing oxidative stress and activating protective antioxidant systems in normal tissues.
  3. NF-κB and inflammatory survival signaling inhibition, with context-dependent suppression of TNF-α, IL-6, COX-2 and related inflammatory mediators.
  4. Mitochondrial/intrinsic apoptosis activation through ↓ mitochondrial membrane potential, ↑ BAX:BCL-2 ratio, cytochrome-c release and caspase activation.
  5. STAT3/JAK signaling suppression, reducing survival, stemness, inflammatory signaling and immune-evasion phenotypes in several tumor models.
  6. EMT, migration and invasion suppression through modulation of E-cadherin, N-cadherin, vimentin, MMP2/MMP9, FAK, YAP/TAZ and related pathways.
  7. Cell-cycle arrest through suppression of cyclins/CDKs and context-dependent induction of p21/p27 and p53 signaling.
  8. Metabolic and hypoxic adaptation inhibition, including HIF-1α, PKM2, HK2 and glycolytic signaling in selected models.
  9. Epigenetic modulation, including reported inhibition of DNMTs, HDAC-associated signaling and EZH2 in selected cancer models.
  10. Additional context-dependent cell-death mechanisms including ER stress, autophagy, ferroptosis and pyroptosis.

Bioavailability / PK relevance: Oral luteolin has poor aqueous solubility and unfavorable systemic availability of unconjugated aglycone. It is absorbed from the intestine but undergoes extensive intestinal and hepatic glucuronidation and sulfation. Animal studies report low absolute bioavailability of free luteolin, commonly in the low-single-digit to low-tens percentage range depending on formulation and analytical definition. Nanoemulsions, lipid/phospholipid systems, cyclodextrins, nanoparticles and other delivery systems can substantially improve exposure experimentally. Luteolin and particularly some circulating conjugates can interact with OATP1B1/OATP2B1 transporters; in-vitro CYP inhibition has also been reported, making pharmacokinetic drug interactions plausible at sufficiently high exposure.

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 10–100 µM luteolin, often 20–50 µM or higher. These concentrations generally exceed sustained concentrations of free luteolin expected after conventional oral dietary or supplemental dosing because extensive conjugation limits circulating aglycone. Consequently, direct translation of many cell-culture IC50 values to standard oral supplementation is weak. Local gastrointestinal exposure, metabolites, tissue deconjugation and optimized formulations may partly alter this limitation.

Clinical evidence status: Predominantly preclinical, but no longer exclusively preclinical. A 2025 single-arm phase I study administered luteolin 50 mg/day for six months to five men with localized prostate cancer undergoing active surveillance; no treatment-related adverse events were reported, but the study was far too small and uncontrolled to establish anticancer efficacy. A larger phase II single-arm multicenter Japanese study of 50 mg/day for one year is currently recruiting with a planned enrollment of 40 patients. Luteolin is therefore best categorized as early-human/phase I–II investigational evidence, not established cancer therapy. Preclinical evidence for chemotherapy and radiotherapy sensitization is substantial but remains cancer-, drug- and genotype-dependent.


-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↓">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

-"Additionally, when reacted with concentrated sulfuric acid, a zinc salt is produced, resulting in a dark red and yellow solution. These color changes serve as a strong basis for the identification of luteolin"

Common Dietary and Plant Sources of Luteolin

Source Luteolin Content Approximate Equivalent Relative Source Level Notes
Bird chili 1035 mg/kg 103.5 mg/100 g Very high Highest source in the cited quantitative food table; concentration may vary substantially by cultivar, maturity and analytical method.
Belimbi leaves 464.5 mg/kg 46.45 mg/100 g Very high Leaf material; not a common Western dietary source.
Onion leaves 391 mg/kg 39.1 mg/100 g Very high Green onion/scallion-type leaf tissue can contain substantially more luteolin than onion bulbs.
Belimbi fruit 202 mg/kg 20.2 mg/100 g High Tropical fruit source.
Dried asam gelugur 107.5 mg/kg 10.75 mg/100 g High Dried plant material; dry-weight concentration is not directly comparable with fresh vegetables.
Celery 80.5 mg/kg 8.05 mg/100 g High One of the most commonly cited dietary sources of luteolin; content differs among celery varieties and plant parts.
Broccoli 74.5 mg/kg 7.45 mg/100 g High Common dietary source. Other compositional surveys report a broad range, indicating strong cultivar and methodology effects.
Carrot 37.5 mg/kg 3.75 mg/100 g Moderate Common dietary source; luteolin may occur predominantly in glycosylated forms.
Green chili 33 mg/kg 3.3 mg/100 g Moderate Content varies substantially among Capsicum species and cultivars.
Limau purut leaves 30.5 mg/kg 3.05 mg/100 g Moderate Kaffir lime leaves; primarily used as a culinary herb rather than consumed in large quantities.
French bean 11 mg/kg 1.1 mg/100 g Low to moderate Common food source but substantially lower than celery, broccoli or onion leaves in the cited dataset.
White radish 9 mg/kg 0.9 mg/100 g Low Lower-luteolin dietary source in the cited dataset.
Parsley Approximately 19.75 mg/100 g dried Approximately 197.5 mg/kg dried High Frequently cited as a rich luteolin-containing herb. Dry-weight values should not be compared directly with fresh-weight vegetables.
Thyme Approximately 51 mg/100 g Approximately 510 mg/kg Very high Herb source reported in reviews; intake per serving is usually small despite the high concentration.
Peppermint Approximately 11.33 mg/100 g fresh Approximately 113.3 mg/kg High Fresh peppermint is a relatively concentrated herbal source.
Spinach Approximately 1.11 mg/100 g Approximately 11.1 mg/kg Low to moderate Common dietary source but lower than many herbs and celery-family plants.
Cabbage Approximately 0.4–0.6 mg/100 g Approximately 4–6 mg/kg Low Widely consumed but generally a relatively dilute luteolin source.
Black olives Approximately 3.2–17.5 mg/100 g Approximately 32–175 mg/kg Moderate to high Luteolin concentration depends strongly on olive cultivar and processing.
Green olives Approximately 0.2–1.2 mg/100 g Approximately 2–12 mg/kg Low to moderate Generally reported at lower concentrations than black olives.
Apple peel Variable Not consistently quantified Low to moderate Luteolin is reported principally in the peel rather than the flesh; concentration is cultivar-dependent.
Chrysanthemum flowers Variable Not consistently quantified Potentially high Traditional medicinal/tea source containing luteolin and luteolin glycosides.


Luteolin — Cancer Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 PI3K / AKT / mTOR survival signaling ↓ PI3K; ↓ p-AKT; ↓ mTOR ↔ / adaptive modulation R–G ↓ survival and proliferation; ↑ cell death One of the most recurrent anticancer signaling effects; confirmed in multiple tumor systems and newer NSCLC studies.
2 ROS and antioxidant defense ↑ ROS; ↓ SOD/GSH/NRF2/HO-1 (context-dependent) ↓ ROS; ↑ antioxidant defenses (context-dependent) P–R Selective oxidative stress in susceptible tumors Biphasic and highly context-dependent. ROS generation can be mechanistically upstream of NF-κB inhibition, JNK activation, apoptosis and radiosensitization.
3 NRF2 / HO-1 antioxidant survival axis ↓ NRF2; ↓ HO-1 (model-dependent) ↑ NRF2; ↑ HO-1 (model-dependent) R–G ↓ tumor antioxidant capacity and drug resistance Especially relevant in NRF2-high cancer cells. Luteolin has sensitized tumor cells to chemotherapy through NRF2 suppression, whereas NRF2 activation contributes to normal-tissue protection.
4 NF-κB inflammatory survival signaling ↓ NF-κB; ↓ inflammatory survival signaling ↓ pathological NF-κB activation R–G ↑ apoptosis; ↓ inflammation and survival ROS accumulation can participate upstream in some tumor models; not all NF-κB inhibition requires ROS.
5 Mitochondria and intrinsic apoptosis ↓ MMP; ↑ BAX; ↓ BCL-2; ↑ Cyt-c; ↑ caspase-9/3 ↔ / ↓ mitochondrial injury under oxidative-stress conditions R–G ↑ mitochondrial apoptosis A common downstream execution mechanism following AKT inhibition, ROS elevation or ER stress.
6 JAK / STAT3 signaling ↓ STAT3; ↓ p-STAT3 ↔ / ↓ inflammatory STAT3 R–G ↓ proliferation, stemness and immune escape Recent work also links PRDX2 inhibition to JAK2/STAT3 suppression and ↓ PD-L1 in lung adenocarcinoma.
7 EMT and metastatic signaling ↓ EMT; ↑ E-cadherin; ↓ N-cadherin; ↓ vimentin; ↓ MMP2/9 ↔ G ↓ migration, invasion and metastasis PI3K/AKT, TGF-β/Smad, YAP/TAZ, FAK and related axes contribute depending on tumor type.
8 Cell-cycle control ↑ G1 or G2/M arrest; ↓ cyclins/CDKs; ↑ p21/p27 ↔ (model-dependent) G ↓ proliferation Cell-cycle phase varies with tumor lineage and concentration.
9 p53 / JNK apoptotic signaling ↑ JNK; ↑ p53 stability/activity (context-dependent) ↔ R–G ↑ apoptosis and chemotherapy response Cisplatin sensitization can depend strongly on functional p53.
10 Glycolysis and metabolic adaptation ↓ glycolysis; ↓ PKM2; ↓ HK2; ↓ ATP (model-dependent) ↔ G ↓ metabolic support for proliferation Not universal across cancers; strongest evidence comes from selected hepatocellular and other metabolically dependent models.
11 HIF-1α and hypoxic adaptation ↓ HIF-1α; ↓ hypoxic adaptation ↔ G ↓ angiogenesis and hypoxia tolerance Reported in breast, colon and other cancer models; linked to reduced VEGF signaling.
12 VEGF and angiogenesis ↓ VEGF; ↓ VEGFR signaling ↔ / anti-inflammatory vascular effects G ↓ tumor angiogenesis Predominantly preclinical evidence.
13 ER stress and unfolded protein response ↑ PERK/eIF2α/ATF4/CHOP; ↑ ER stress (model-dependent) ↓ pathological ER stress in several injury models R–G ↑ tumor cell death Illustrates luteolin's frequently opposite stress response in malignant versus nonmalignant models.
14 Autophagy ↑ Beclin-1; ↑ LC3-II; ↓ p62 (context-dependent) ↔ / protective modulation G Autophagic stress or contribution to cell death Can be cytotoxic or cytoprotective depending on cancer model and treatment context.
15 GPX4-dependent ferroptosis ↓ GPX4; ↓ GSH; ↑ lipid oxidation; ↑ ferroptosis ↔ / ↓ ferroptotic injury in some normal-tissue models R–G ↑ ferroptotic cancer-cell death Recent colon-cancer work supports GPX4-linked ferroptosis plus enhanced antitumor immune activation.
16 Epigenetic regulation ↓ DNMT activity; ↓ HDAC-associated signaling; ↓ EZH2 (model-dependent) ↔ / context-dependent G Re-expression of growth-suppressive programs Mechanistically interesting but less broadly established than AKT, redox and inflammatory pathways.
17 YAP / Wnt and tumor immunity ↓ YAP; ↓ Wnt-associated signaling; ↓ immune escape ↑ CTL functional activity indirectly G ↑ antitumor T-cell effectiveness 2025 animal work suggests luteolin can enhance tumor-specific CTL therapy; clinical relevance remains unproven.
18 Chemosensitization ↑ response to cisplatin and several other agents (drug-dependent) Variable; possible tissue protection in other contexts G ↓ treatment resistance Mechanisms include ↓ NRF2, ↓ AKT, ↑ p53/JNK, mitochondrial apoptosis and suppression of resistance pathways. Evidence remains predominantly preclinical.
19 Radiosensitization ↑ radiation-induced ROS and apoptosis Potential radioprotection reported in nonmalignant models R–G ↑ radiation response In NSCLC models, p38/ROS/caspase signaling increased radiosensitivity; tumor versus normal-tissue effects require careful context separation.
20 Clinical Translation Constraint High in-vitro concentrations often required Systemic exposure dominated by conjugated metabolites G Limits translation of cell-culture potency Poor aqueous solubility, extensive phase-II metabolism, formulation dependence, possible transporter/drug interactions and extremely limited controlled human oncology evidence remain major constraints.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr



Luteolin — Alzheimer’s disease relevance: Luteolin has substantial preclinical neuroprotective evidence and is sufficiently relevant to Alzheimer’s disease to warrant a separate database section. Reported effects include ↓ amyloid-β production/accumulation, ↓ BACE1-associated amyloidogenic processing, ↓ tau hyperphosphorylation, ↓ neuroinflammation, ↓ oxidative stress, ↓ NLRP3/NF-κB signaling and ↑ BDNF/TrkB-associated neuroplasticity. Acetylcholinesterase inhibition has also been reported. However, evidence remains predominantly cellular and animal; convincing disease-modifying clinical evidence in Alzheimer’s disease is absent. Oral bioavailability and blood-brain exposure of free luteolin remain important translational constraints.

Clinical evidence status: Preclinical. Contemporary reviews identify Alzheimer’s disease as the neurodegenerative disorder in which luteolin has been studied most extensively, but explicitly note that clinical therapeutic evidence remains deficient.

Luteolin — Alzheimer’s Disease Mechanisms

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 Neuroinflammation / NF-κB ↓ NF-κB; ↓ IL-1β; ↓ IL-6; ↓ TNF-α ↓ chronic neuroinflammation Among the most consistently proposed neuroprotective actions.
2 Amyloid-β pathology ↓ Aβ; ↓ Aβ42 ↓ amyloid burden Supported predominantly by cellular and animal studies.
3 BACE1 / amyloidogenic processing ↓ BACE1 ↓ amyloidogenic APP processing Potential upstream mechanism contributing to reduced Aβ generation.
4 Tau phosphorylation ↓ p-tau ↓ tau pathology Multiple preclinical models report reduced abnormal tau phosphorylation.
5 Oxidative stress / NRF2 ↓ ROS; ↑ NRF2; ↑ antioxidant defenses ↓ neuronal oxidative injury Direction differs from the pro-oxidant effect frequently exploited in cancer cells.
6 NLRP3 inflammasome ↓ NLRP3 ↓ inflammasome-driven neuronal inflammation Potential bridge between redox stress and neuroinflammation.
7 BDNF / TrkB neuroplasticity ↑ BDNF; ↑ TrkB ↑ synaptic and neuronal support Observed in several neurobehavioral models.
8 Acetylcholinesterase ↓ AChE ↑ cholinergic signaling Primarily biochemical/preclinical evidence; clinical magnitude is unknown.
9 Neuronal apoptosis and mitochondrial stress ↓ apoptosis; ↓ mitochondrial injury ↑ neuronal survival Opposite phenotypic direction from luteolin-induced apoptosis in many cancer models.
10 Clinical Translation Constraint Low free-luteolin exposure; limited human CNS data Uncertain clinical efficacy Human Alzheimer’s disease efficacy trials are insufficient; brain exposure and formulation remain unresolved.


NF-kB, Nuclear factor kappa B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.
Scientific Papers found: Click to Expand⟱
8368- LT,    A critical role of luteolin-induced reactive oxygen species in blockage of tumor necrosis factor-activated nuclear factor-kappaB pathway and sensitization of apoptosis in lung cancer cells
- in-vitro, Lung, NA
NF-kB↓, Luteolin, a naturally occurring polyphenol flavonoid, has been reported to sensitize colorectal cancer cells to TNF-induced apoptosis through suppression of NF-kappaB
ROS↑, reactive oxygen species (ROS) accumulation induced by luteolin in modulating TNF-activated pathways in lung cancer cells.
JNK↑, whereas it potentiated the c-Jun N-terminal kinase (JNK) to increase apoptosis induced by TNF in lung cancer cells
Apoptosis↑,
SOD↓, luteolin induced an early phase ROS accumulation via suppression of the cellular superoxide dismutase activity.
eff↓, suppression of ROS accumulation by ROS scavengers butylated hydroxyanisole, and N-acetyl-L-cysteine (NAC) prevented the luteolin-induced suppression of NF-kappaB

8382- LT,    Luteolin as a dietary flavonoid for brain health: modulating neuroinflammation and cognitive decline in neurodegenerative disorders
- Review, AD, NA - Review, Park, NA
*neuroP↑, been recognized as a potentially effective neuroprotective nutraceutical because of its remarkable anti-inflammatory, antioxidant, and neurotrophic properties.
*Inflam↓,
*antiOx↑,
*NF-kB↓, Luteolin significantly inhibits microglial activation, reduces pro-inflammatory cytokine production, modulates the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, and enhances Nrf2-mediated antioxidant
*NRF2↑,
*BDNF↑, promotes synaptic plasticity through brain-derived neurotrophic factor (BDNF)-associated pathways
*cognitive↑, Preclinical studies consistently demonstrate substantial improvements in cognitive function, motor performance, demyelination, and neuronal viability in models of AD, PD, MS, and HD.
*motorD↑,
*BBB↑, Accumulating preclinical and nascent clinical evidence indicates that luteolin is able to cross the blood-brain barrier (BBB), reducing neuroimmune activation, promoting neuronal viability, and enhancing cognitive performance in models of AD, PD, and
*BioAv↓, The absolute oral bioavailability of luteolin is quite low due to its limited solubility and rapid metabolism; yet, its metabolites preserve considerable biological activity that may enhance its neuroprotective properties
*NO↓, curtails the production of nitric oxide and reactive oxygen species (ROS)
*ROS↓,
*NRF2↑, Numerous investigations reveal that luteolin stimulates the Nrf2/ARE pathway, enhancing the production of phase II antioxidant enzymes and thus fortifying cellular endurance against ROS
*ARE↑,
*MMP↑, At the mitochondrial level, luteolin protects membrane potential, decreases ROS generation, and limits permeability transition; these actions collectively support ATP synthesis
*BDNF↑, luteolin may elevate the levels of brain-derived neurotrophic factor (BDNF) and amplify the downstream tropomyosin receptor kinase B signaling,
*Learn↑, protective actions converge to enhance learning and memory across various animal models exhibiting cognitive deficits.
*memory↑,
*cognitive↑,
*p‑JNK↓, Luteolin (80 mg/kg/day, i.c.v.) AD mice (Aβ1-42 oligomers injected) Cognitive impairment ↓, p-JNK ↓, p38 MAPK ↓, GFAP ↓, Iba-1 ↓, TNF-α ↓, IL-1β ↓, Bax ↓, Bcl-2 ↑, Caspase-3 ↓, Cox-2 ↓, BACE-1 ↓, Aβ1-42 ↓, PSD-95 ↑, SN
*GFAP↓,
*AIF1/Iba-1↓,
*TNF-α↓,
*IL1β↓,
*BAX↓,
*COX2/PTGS2↓,
*BACE/β-secretase↓,
*Aβ42↓,
*PSD95↑,
*SNAP25↑, SNAP-25 ↑
*lipid-P↓, Luteolin (5, 10, 15, 20 μM in diet) Transgenic Drosophila expressing human Aβ42 Lifespan ↑, climbing ability ↑, activity ↑, LPO ↓, PCC ↓, GST ↓, GSH ↑, SOD ↓, CAT ↓, AChE ↓, caspase-3/9 ↓, Aβ42 plaque ↓
*GSTs↓,
*GSH↑,
*SOD↓,
*Catalase↓,
*AChE↓,
*Casp3↓,
*Casp9↓,

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

8393- LT,    Progress, pharmacokinetics and future perspectives of luteolin modulating signaling pathways to exert anticancer effects: A review
- Review, Var, NA
TumCP↓, induce apoptosis, inhibition of tumor cell proliferation and metastasis, anti-angiogenesis, reversal of epithelial-mesenchymal transition, regulation of immune function, synergism with anti-cancer drugs and regulation of reactive oxygen species level
TumMeta↓,
angioG↓,
EMT↓,
Imm↝,
ChemoSen↑,
*Inflam↓, Luteolin are known for their natural anti-inflammatory properties,
*COX2/PTGS2↓, It inhibits the synthesis and activity of COX-2, a key enzyme in prostaglandins.
*NF-kB↓, luteolin can also inhibit the activation of nuclear factor Kappa-light-chain-enhancer of activated B cells (NF-κB)
MMP2↓, luteolin significantly decreased the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) whilst also inhibiting the phosphorylation of AKT and PI3K
MMP9↓,
p‑Akt↓,
p‑PI3K↓,
IGF-2↓, insulin-like growth factor 2 (IGF-2) and insulin growth factor receptor 1 (IGF-1R) were significantly reduced in human colon cancer cells (HT-29) treated with luteolin,
IGF-1R↓,
CXCL16↓, luteolin reduced the mRNA levels of CXC chemokine ligand 16 (CXCL16) to inhibit the PI3K/AKT pathway
NOTCH1↓, this anti-tumor effect may be associated with a reduction in key factors that promote tumor development such as Notch-1, Hes-1, VEGF, and MMPs
HES1↓,
VEGF↓,
ROS↑, Ju et al[86] found that Luteolin can lead to the accumulation of ROS,

8401- LT,    Multi-Faceted Role of Luteolin in Cancer Metastasis: EMT, Angiogenesis, ECM Degradation and Apoptosis
- Review, Var, NA
EMT↓, The flavone interferes with the epithelial-mesenchymal transition (EMT) by inhibiting the expression of N-cadherin, vimentin
N-cadherin↓,
Vim↓,
VEGF↓, mainly by blocking the VEGF/VEGFRs signaling pathway and by inhibiting MMPs.
VEGFR1↓,
MMPs↓,
Telomerase↓, Reduction of telomerase expression by targeting NF-κB/c-Myc; increase of Bax/Bcl-2 ratio and caspase-3
NF-kB↓,
cMyc↓,
Bax:Bcl2↑,
Casp3↑,
PI3K↓, Repression of PI3K/Akt pathway; induction of FOXO3a expression and increase of p21 and p27; induction of PARP cleavage and release of cytochrome c
Akt↓,
FOXO3↑,
P21↑,
p27/CDKN1B↑,
cl‑PARP↑,
Cyt‑c↑,
NOTCH↓, Repression of Notch signaling and its downstream targets Notch-1, Hes-1, VEGF
HES1↓,
ROS↑, Induction of ROS accumulation via suppression of SOD activity;
SOD↓,
miR-34b-5p↑, Upregulation of miR-34a-5p
Hif1a↓, inhibition of HIF-1α/VEGF axis
P21↓, downregulation of p21, survivin, Mcl-1, Bcl-x(L) and Mdm-2
survivin↓,
Mcl-1?,
Bcl-xL↓,
MDM2↓,
MMP2↓, Downregulation of MMP-2, -9, -3 and -16 expression coupled with an enhancement of miR-384
MMP9↓,
MMP3↓,
MMP16↓,
miR-384↑,
NRF2↓, Inhibition of Nrf2
HO-1↓, downregulation of the antioxidant genes γ-glutamylcysteine ligase and heme oxygenase-1,
angioG↓, Luteolin Suppresses Angiogenesis

8397- LT,    Effects and Mechanisms of Luteolin, a Plant-Based Flavonoid, in the Prevention of Cancers via Modulation of Inflammation and Cell Signaling Molecules
- Review, Var, NA
tumCV↓, The studies have confirmed that luteolin can inhibit cancer-cell survival and proliferation, angiogenesis, invasion, metastasis, mTOR/PI3K/Akt, STAT3, Wnt/β-catenin, and cell-cycle arrest, and induce apoptosis.
TumCP↓,
angioG↓,
TumCI↓,
TumMeta↓,
mTOR↓,
PI3K↓,
Akt↓,
STAT3↓,
Wnt↓,
β-catenin/ZEB1↓,
TumCCA↑,
Apoptosis↑,
hTERT/TERT↓, after 24 h of treatment with luteolin at concentrations of 10 and 30 µM, the mRNA expression levels of hTERT were significantly downregulated
AP-1↓, down-regulation of nuclear AP-1 and NF-κB and the inhibition of the MAPK signaling pathway.
NF-kB↓,
MAPK↓,
HSP90↓, luteolin was observed to reduce the association between the androgen receptor and heat-shock protein 90, ultimately leading to AR degradation
AR↓,
IGF-1R↓, luteolin inhibited IGF-1R/AKT signaling
Akt↓,
NOTCH↓, Luteolin may inhibit Notch signaling by regulating miRNAs.
IL6↓, inhibiting the IL-6/STAT3 signaling pathway
MMP2↓, luteolin was found to visibly downregulate the expressions of MMP-2, MMP-3, MMP-9, and MMP-16.
MMP3↓,
MMP9↓,
MMP16↓,
TumVol∅, consumption of luteolin did not appear to affect tumor growth in vivo, as no significant differences were observed in tumor volume or weight
TumW∅,
miR-34a↑, BGC-823 and SGC-7901 Upregulation of miR-34a
miR-107↑, MKN45 or BGC823 Upregulated miR-107, miR-34a and miR-139
miR-139-5p↑,
miR-422a↑, MKN45 or BGC823 Upregulated miR-34a and miR-422a
miR-21↓, MKN45 or BGC823 Downregulated miR-21, miR-155
miR-155↓,
miR-224↓, MKN45 or BGC823 Downregulated miR-224, miR-340
miR-340↓,
*toxicity↓, 100 mg/kg of luteolin did not cause any liver or kidney toxicity, which indicates a favorable safety profile for luteolin

8387- LT,  QC,  Api,  Ba,    Identification of Flavonoid Compounds in Treating Alzheimer's Disease Based on Network Medicine Framework Strategy
- in-vitro, AD, NA
*neuroP↑, luteolin, quercetin, apigenin (API), and baicalein demonstrated significant neuroprotective effects in A[Formula: see text]25-35-induced rat pheochromocytoma (PC12) cell models.
*MMP↑, API treatment impeded the H2O2-induced decline in the mitochondrial membrane potential of PC12 cells, suppressed apoptosis, and mitigated neuronal damage.
*Apoptosis↓,
*Akt↓, Furthermore, API downregulated the AKT/NF-[Formula: see text]B signal pathway, promoted microglial M2 polarization, and attenuated LPS-induced neuroinflammation in BV2 cells.
*NF-kB↓,
*pol-M2 MC↑,
*NeuroI↓,

8384- LT,    Current situation and research progress of luteolin in the treatment of gastrointestinal malignant tumors
- Review, GC, NA
Apoptosis↑, inducing tumor cell apoptosis, promoting autophagy, arresting the cell cycle, inhibiting epithelial-mesenchymal transition (EMT), enhancing tumor cell peroxidation,
TumAuto↑,
TumCCA↑,
EMT↓,
*ROS↓, luteolin to modulate the activity of reactive oxygen species (ROS) scavenging enzymes, act as an antioxidant, regulate pro-inflammatory factors,
*antiOx↑,
ROS↑, Intriguingly, luteolin can also exhibit pro-oxidative effects and demonstrate anticancer properties under specific circumstances
P53↑, luteolin activates the p53 signaling pathway, leading to apoptosis and cell cycle arrest in CRC
LC3II↑, luteolin increases levels of LC3-II and Beclin 1 proteins in a p53-dependent manner
Beclin-1/ATG6↑,
p‑MAP2K1/MEK1↓, luteolin reduces the expression of p-MEK 1 and p-ERK 1/2 in CRC cells in a dose-dependent manner.
p‑ERK↓,
BAX↑, followed by upregulation of apoptosis-related proteins BAX and cleaved Caspase-3, and downregulation of Bcl-2.
cl‑Casp3↑,
Bcl-2↓,
p‑MAPK↓, CRC cells by inhibiting phosphorylation of the MAPK pathway.
DNArepair↓, luteolin downregulates DNA repair proteins, such as HMGB1, LIG, and XRCC1, while upregulating ERCC-3, resulting in DNA single-strand breaks and ultimately apoptosis.
HMGB1↓,
XRCC1↓,
ERCC3↑,
CycB/CCNB1↓, research reveals that luteolin treatment decreases levels of G2-M phase-related proteins Cyclin B1 and CDC2, while increasing p-CHK1 in a concentration-dependent manner.
CDC2↓,
p‑CHK1↑,
TumCCA↑, This indicates that luteolin can induce G2/M phase arrest in CRC cells, thereby inhibiting CRC cell proliferation
TumCP?,
Wnt↓, luteolin dose-dependently suppressed the expression of Wnt3 and β-catenin in CRC cells.
β-catenin/ZEB1↓,
miR-384↑, inhibition of PTN expression by luteolin through upregulation of miR-384.
PTN↓,
MMP2↓, The decrease of PTN expression finally inhibited the expression of matrix metalloproteinases MMP-2, MMP-3, MMP-9 and MMP-16 related to tumor migration
MMP3↓,
MMP9↓,
MMP16↓,
Ferroptosis↑, Ferroptosis is also one of the most important ways that luteolin exerts its anti-CRC effect.
GPx4↓, luteolin further reduced the expression of tumor survival-related protein GPX4 by up-regulating the expression of HIC1 in CRC cells
Synergy↑, luteolin significantly reduced tumor mass and volume by combining with Erastin, and significantly down-regulated the expression of Ki67 and GSH in tumor tissues.
Ki-67↓,
GSH↓,
ChemoSen↑, luteolin is used in combination with some chemotherapeutic drugs, luteolin can mediate multiple pathways such as cell apoptosis, autophagy, and inhibition of angiogenesis, improving the sensitivity of CRC cells to chemotherapeutic drugs.
TumCP↓, Luteolin can inhibit the proliferation, migration, invasion and drug resistance of GC cells by inhibiting PI3K/AKT/mTOR, NF-κB, Notch, MAPK and other classical pathways.
TumCMig↓,
TumCI↓,
PI3K↓,
Akt↓,
mTOR↓,
NF-kB↓,
NOTCH↓,
miR-139-5p↑, promoting the expression of tumor suppressor miR-139, miR-34a, miR-422a and miR-107, inhibiting the expression of tumor promoter miR-21, miR-155, miR-224 and miR-340,
miR-34a↑,
miR-422a↑,
miR-107↑,
miR-21↓,
miR-155↓,
miR-224↓,
miR-340↓,
E-cadherin↑, promoting the expression of E-cadherin by inhibiting tumor migration-related proteins MMP2, MMP9, N-cadherin and vimentin.
N-cadherin↓,
Vim↓,
HK1↓, inhibiting the expression of HK1, p-MAPK and p-ERK, promoting the expression of P53 and P21, inducing G1 phase arrest of GC cells
FOXO1↓, inhibit GC cells by up-regulating FOXO1 expression
compI↓, inhibit the activity of METC Complexes I, III and V at the same time, destroy mitochondrial outer membrane by down -regulating Bcl-2 and up-regulating Bax protein, and then induce apoptosis
compIII↓,
compV↓,
ETC↓,
BioAv↝, Due to the poor water solubility and low bioavailability of luteolin, Karole et al. studied to improve the bioavailability of luteolin in order to enhance the therapeutic effect by non-invasively overcoming the intestinal epithelial barrier through l

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/β-secretase↓, 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.
*Synergy↑, 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

2906- LT,    Luteolin, a flavonoid with potentials for cancer prevention and therapy
- Review, Var, NA
*Inflam↓, anti-inflammation, anti-allergy and anticancer, luteolin functions as either an antioxidant or a pro-oxidant biochemically
AntiCan↑,
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
Apoptosis↑, induction of apoptosis, and inhibition of cell proliferation, metastasis and angiogenesis.
TumCP↓,
TumMeta↓,
angioG↓,
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)
Akt↓,
NF-kB↓,
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
P53↑, stimulating apoptosis pathways including those that induce the tumor suppressor p53
*ROS↓, Direct evidence showing luteolin as a ROS scavenger was obtained in cell-free systems
*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)
*GSR↑,
*SOD↑,
*Catalase↑,
*other↓, luteolin may chelate transition metal ions responsible for the generation of ROS and therefore inhibit lipooxygenase reaction, or suppress nontransition metal-dependent oxidation
ROS↑, Luteolin has been shown to induce ROS in untransformed and cancer cells
Dose↝, It is believed that flavonoids could behave as antioxidants or pro-oxidants, depending on the concentration and the source of the free radicals
chemoP↑, may act as a chemopreventive agent to protect cells from various forms of oxidant stresses and thus prevent cancer development
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
JNK↑,
p27/CDKN1B↑, Table 1
P21↑,
DR5↑,
Casp↑,
Fas↑,
BAX↑,
MAPK↓,
CDK2↓,
IGF-1↓,
PDGF↓,
EGFR↓,
PKCδ↓,
TOP1↓,
TOP2↓,
Bcl-xL↓,
FASN↓,
VEGF↓,
VEGFR2/KDR/Flk1↓,
MMP9↓,
Hif1a↓,
FAK↓,
MMP1↓,
Twist↓,
ERK↓,
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
CYP1A1↓,
CYP1A2↓,
TumCCA↑, Luteolin is able to arrest the cell cycle during the G1 phase in human gastric and prostate cancer, and in melanoma cells

2921- LT,    Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies
- Review, Nor, NA
*hepatoP↑, Due to its excellent liver protective effect, luteolin is an attractive molecule for the development of highly promising liver protective drugs.
*AMPK↑, fig2
*SIRT1↑,
*ROS↓,
STAT3↓,
TNF-α↓,
NF-kB↓,
*IL2↓,
*IFN-γ↓,
*GSH↑,
*SREBP1/SREBF1↓,
*ZO-1↑,
*TLR4↓,
BAX↑, anti cancer
Bcl-2↓,
XIAP↓,
Fas↑,
Casp8↑,
Beclin-1/ATG6↑,
*TXNIP↓, luteolin inhibited TXNIP, caspase-1, interleukin-1β (IL-1β) and IL-18 to prevent the activation of NLRP3 inflammasome, thereby alleviating liver injury.
*Casp1↓,
*IL1β↓,
*IL18↓,
*NLRP3↓,
*MDA↓, inhibiting oxidative stress and regulating the level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)
*SOD↑,
*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)
*ER Stress↓, down regulate the formation of nitrotyrosine (NT) and endoplasmic reticulum (ER) stress induced by acetaminophen, and alleviate liver injury
*ALAT↓, ↓ALT, AST, MDA, iNOS, NLRP3 ↑GSH, SOD, Nrf2
*AST↓,
*iNOS↓,
*IL6↓, ↓TXNIP, NLRP3, TNF-α, IL-6 ↑HO-1, NQO1
*HO-1↑,
*NQO1↑,
*PPARα↑, ↓TNF-α, IL-6 IL-1β, Bax ↑PPARα
*ATF4↓, ↓ALT, AST, TNF-α, IL-6, MDA, ATF-4, CHOP ↑GSH, SOD
*CHOP/DDIT3↓,
*Inflam↓, Luteolin ameliorates MAFLD through anti-inflammatory and antioxidant effects
*antiOx↑,
*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

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
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
TumCCA↑, luteolin could promote cell cycle arrest and apoptosis in HuH-7 cells
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)
ATF2↓,
NF-kB↓,
GSK‐3β↓,
cMyc↓,
GSTs↓, expression change of NQO-1, GSTs, and TRXR1 indicated the increase in ROS
TrxR1↓,
ROS↑,

2919- LT,    Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence
- Review, Var, NA
RadioS↑, it can be used as an adjuvant to radio-chemotherapy and helps to ameliorate cancer complications
ChemoSen↑,
chemoP↑,
*lipid-P↓, ↓LPO, ↑CAT, ↑SOD, ↑GPx, ↑GST, ↑GSH, ↓TNF-α, ↓IL-1β, ↓Caspase-3, ↑IL-10
*Catalase↑,
*SOD↑,
*GPx↑,
*GSTs↑,
*GSH↑,
*TNF-α↓,
*IL1β↓,
*Casp3↓,
*IL10↑,
NRF2↓, Lung cancer model ↓Nrf2, ↓HO-1, ↓NQO1, ↓GSH
HO-1↓,
NQO1↓,
GSH↓,
MET↓, Lung cancer model ↓MET, ↓p-MET, ↓p-Akt, ↓HGF
p‑MET↓,
p‑Akt↓,
HGF/c-Met↓,
NF-kB↓, Lung cancer model ↓NF-κB, ↓Bcl-XL, ↓MnSOD, ↑Caspase-8, ↑Caspase-3, ↑PARP
Bcl-2↓,
SOD2↓,
Casp8↑,
Casp3↑,
PARP↑,
MAPK↓, LLC-induced BCP mouse model ↓p38 MAPK, ↓GFAP, ↓IBA1, ↓NLRP3, ↓ASC, ↓Caspase1, ↓IL-1β
NLRP3↓,
ASC↓,
Casp1↓,
IL6↓, Lung cancer model ↓TNF‑α, ↓IL‑6, ↓MuRF1, ↓Atrogin-1, ↓IKKβ, ↓p‑p65, ↓p-p38
IKKα↓,
p‑p65↓,
p‑p38↑,
MMP2↓, Lung cancer model ↓MMP-2, ↓ICAM-1, ↓EGFR, ↓p-PI3K, ↓p-Akt
ICAM-1↓,
EGFR↑,
p‑PI3K↓,
E-cadherin↓, Lung cancer model ↑E-cadherin, ↑ZO-1, ↓N-cadherin, ↓Claudin-1, ↓β-Catenin, ↓Snail, ↓Vimentin, ↓Integrin β1, ↓FAK
ZO-1↑,
N-cadherin↓,
CLDN1↓,
β-catenin/ZEB1↓,
Snail↓,
Vim↑,
ITGB1↓,
FAK↓,
p‑Src↓, Lung cancer model ↓p-FAK, ↓p-Src, ↓Rac1, ↓Cdc42, ↓RhoA
Rac1↓,
Cdc42↓,
Rho↓,
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
Tyro3↓, Lung cancer model ↓TAM RTKs, ↓Tyro3, ↓Axl, ↓MerTK, ↑p21
AXL↓,
CEA↓, B(a)P induced lung carcinogenesis ↓CEA, ↓NSE, ↑SOD, ↑CAT, ↑GPx, ↑GR, ↑GST, ↑GSH, ↑Vitamin E, ↑Vitamin C, ↓PCNA, ↓CYP1A1, ↓NF-kB
NSE↓,
SOD↓,
Catalase↓,
GPx↓,
GSR↓,
GSTs↓,
GSH↓,
VitE↓,
VitC↓,
CYP1A1↓,
cFos↑, Lung cancer model ↓Claudin-2, ↑p-ERK1/2, ↑c-Fos
AR↓, ↓Androgen receptor
AIF↑, Lung cancer model ↑Apoptosis-inducing factor protein
p‑STAT6↓, ↓p-STAT6, ↓Arginase-1, ↓MRC1, ↓CCL2
p‑MDM2↓, Lung cancer model ↓p-PI3K, ↓p-Akt, ↓p-MDM2, ↑p-P53, ↓Bcl-2, ↑Bax
NOTCH1↓, Lung cancer model ↑Bax, ↑Cleaved-caspase 3, ↓Bcl2, ↑circ_0000190, ↓miR-130a-3p, ↓Notch-1, ↓Hes-1, ↓VEGF
VEGF↓,
H3↓, Lung cancer model ↑Caspase 3, ↑Caspase 7, ↓H3 and H4 HDAC activities
H4↓,
HDAC↓,
SIRT1↓, Lung cancer model ↑Bax/Bcl-2, ↓Sirt1
ROS↑, Lung cancer model ↓NF-kB, ↑JNK, ↑Caspase 3, ↑PARP, ↑ROS, ↓SOD
DR5↑, Lung cancer model ↑Caspase-8, ↑Caspase-3, ↑Caspase-9, ↑DR5, ↑p-Drp1, ↑Cytochrome c, ↑p-JNK
Cyt‑c↑,
p‑JNK↑,
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
mTOR↓,
CD34↓,
FasL↑, Lung cancer model ↑DR 4, ↑FasL, ↑Fas receptor, ↑Bax, ↑Bad, ↓Bcl-2, ↑Cytochrome c, ↓XIAP, ↑p-eIF2α, ↑CHOP, ↑p-JNK, ↑LC3II
Fas↑,
XIAP↓,
p‑eIF2α↑,
CHOP/DDIT3↑,
LC3II↑,
PD-1↓, Lung cancer model ↓PD-L1, ↓STAT3, ↑IL-2
STAT3↓,
IL2↑,
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
cachexia↓, luteolin could be a potential safe and efficient alternative therapy for the treatment of cancer cachexi
BioAv↑, A low-energy blend of castor oil, kolliphor and polyethylene glycol 200 increases the solubility of luteolin by a factor of approximately 83
*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)
*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

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/CCNB1↓,
Casp9↑,
Casp3↑,
Cyt‑c↑,
cycA1/CCNA1↑,
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/TERT↓, Suppress hTERT in MDA‐MB‐231 breast cancer cel
DR5↑, Boost DR5 expression
Beclin-1/ATG6↑, 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
*antiAll↑, Asthma Inhibit the mucus overproduction as well as suppress the GABAA receptors
*Mucositis↓,
*TregCell↑, Decrease inflammation in allergic asthma by activating Treg cells
*Beclin-1/ATG6↓, Inhibit autophagy in pulmonary tissues via restricting beclin1‐PI3KC3 protein complex and activating PI3K/Akt/mTOR signaling pathway
*PI3K↑,
*Akt↑,
*mTOR↑,

2914- LT,    Therapeutic Potential of Luteolin on Cancer
- Review, Var, NA
*antiOx↑, As an antioxidant, Luteolin and its glycosides can scavenge free radicals caused by oxidative damage and chelate metal ions
*IronCh↑,
*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
*BioAv↓, One major problem related to the use of flavonoids for therapeutic purposes is their low bioavailability.
*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
DNAdam↑, Luteolin’s anticancer properties, which involve DNA damage, regulation of redox, and protein kinases in inhibiting cancer cell proliferation
TumCP↓,
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
P53↑,
JNK↑,
BAX↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑PARP↑,
survivin↓, downregulating proteins involved in cell cycle progression, including Survivin, Cyclin D1, Cyclin B, and CDC2, and upregulating p21
cycD1/CCND1↓,
CycB/CCNB1↓,
CDC2↓,
P21↑,
angioG↓, suppress angiogenesis in cancer cells by inhibiting the expression of some angiogenic factors, such as MMP-2, AEG-1, VEGF, and VEGFR2
MMP2↓,
AEG1↓,
VEGF↓,
VEGFR2/KDR/Flk1↓,
MMP9↓, inhibit metastasis by inhibiting several proteins that function in metastasis, such as MMP-2/-9, CXCR4, PI3K/Akt, ERK1/2
CXCR4↓,
PI3K↓,
Akt↓,
ERK↓,
TumAuto↑, can promote the conversion of LC3B I to LC3B II and upregulate Beclin1 expression, thereby causing autophagy
LC3B-II↑,
EMT↓, Luteolin was identified to suppress the epithelial to mesenchymal transition by upregulating E-cadherin and downregulating N-cadherin and Wnt3 expressions.
E-cadherin↑,
N-cadherin↓,
Wnt↓,
ROS↑, DNA damage that is induced by reactive oxygen species (ROS),
NICD↓, Luteolin can block the Notch intracellular domain (NICD) that is created by the activation of the Not
p‑GSK‐3β↓, Luteolin can inhibit the phosphorylation of the GSK3β induced by Wnt, resulting in the prevention of GSK3β inhibition
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)
COX2/PTGS2↓,
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
Ca+2↑, caused loss of the mitochondrial membrane action potential, enhanced levels of mitochondrial calcium (Ca2+),
ChemoSen↑, Luteolin enhanced the effect of one of the most effective chemotherapy drugs, cisplatin, on CRC cells
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
IFN-γ↓, decreased the expression of interferon-gamma-(IFN-γ)
RadioS↑, suggested that Luteolin can act as a radiosensitizer, promoting apoptosis by inducing p38/ROS/caspase cascade
MDM2↓, Luteolin treatment was associated with increased p53 and p21 and decreased MDM4 expressions both in vitro and in vivo.
NOTCH1↓, Luteolin suppressed the growth of lung cancer cells, metastasis, and Notch-1 signaling pathway
AR↓, downregulating the androgen receptor (AR) expression
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.
TIMP2↑,
ER Stress↑, Luteolin caused oxidative stress and ER stress in the Hep3B cells,
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
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)
p‑NF-kB↑,
p‑cMyc↑,
hTERT/TERT↓,
RAS↓, Luteolin was found to suppress the expressions of K-Ras, H-Ras, and N-Ras, which are the activators of PI3K
YAP/TEAD↓, Luteolin caused significant inhibition of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)
TAZ↓,
NF-kB↓, Luteolin was found to have a strong inhibitory effect on the NF-κB
NRF2↓, Luteolin-loaded nanoparticles resulted in a significant reduction in the Nrf2 levels compared to Luteolin alone.
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
MDR1↓,

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/TERT↓, 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/ATG6↓, 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/ATG6↑, 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.

2911- LT,    Luteolin targets MKK4 to attenuate particulate matter-induced MMP-1 and inflammation in human keratinocytes
- in-vitro, Nor, HaCaT
*MMP1↓, luteolin effectively suppressed PM-induced MMP-1 and COX-2 expression and reduced the production of the proinflammatory cytokine IL-6.
*COX2/PTGS2↓,
*IL6↓,
*AP-1↓, luteolin inhibited the activation of AP-1 and NF-κB pathways and decreased reactive oxygen species (ROS) levels in HaCaT cells.
*NF-kB↓,
*ROS↓,
*p‑MKK4↑, luteolin binds directly to mitogen-activated protein kinase kinase (MKK) 4, inhibiting its kinase activity . increases phosphorylation of MKK4
*p‑JNK↓, subsequently reducing the phosphorylation of JNK1/2 and p38 mitogen-activated protein kinase.
*p‑p38↓,


Showing Research Papers: 1 to 17 of 17

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 17

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx⇅, 1,   Catalase↓, 2,   GPx↓, 1,   GPx4↓, 1,   GSH↓, 3,   GSR↓, 1,   GSTs↓, 2,   HO-1↓, 3,   NQO1↓, 1,   NRF2↓, 4,   NRF2↑, 1,   ROS↓, 1,   ROS↑, 10,   SOD↓, 5,   SOD2↓, 1,   Trx1↑, 1,   TrxR1↓, 1,   VitC↓, 1,   VitE↓, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

CDC2↓, 3,   compI↓, 1,   compIII↓, 1,   compV↓, 1,   ETC↓, 1,   mtDam↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

FASN↓, 1,   GSK‐3β↓, 1,   p‑GSK‐3β↓, 1,   HK1↓, 1,   SIRT1↓, 1,  

Cell Death(tgid=5) ⓘ

AIF↑, 1,   APAF1↑, 1,   Apoptosis↑, 5,   ASC↓, 1,   BAD↑, 1,   BAX↑, 6,   Bax:Bcl2↑, 1,   Bcl-2↓, 5,   Bcl-xL↓, 2,   BID↑, 1,   BNIP3↑, 1,   BOK↑, 1,   Casp↑, 1,   Casp1↓, 1,   cl‑Casp12↑, 1,   Casp3↑, 4,   cl‑Casp3↑, 2,   Casp8↑, 2,   cl‑Casp8↑, 1,   Casp9↑, 2,   cl‑Casp9↑, 1,   proCasp9↓, 1,   Cyt‑c↑, 4,   DR5↑, 5,   FADD↑, 1,   Fas↑, 4,   FasL↑, 1,   Ferroptosis↑, 1,   iNOS↓, 1,   Mcl-1?, 1,   Mcl-1↓, 1,   MDM2↓, 3,   p‑MDM2↓, 1,   NAIP↓, 1,   p‑p38↑, 1,   survivin↓, 2,   XIAP↓, 4,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 7,   Akt↑, 1,   p‑Akt↓, 3,   AKT1↓, 2,   Akt2↓, 1,   EGFR↓, 1,   EGFR↑, 1,   p‑EGFR↓, 1,   ERK↓, 2,   p‑ERK↓, 2,   HGF/c-Met↓, 1,   IGF-1R↓, 2,   IKKα↓, 1,   JNK↑, 3,   p‑JNK↑, 1,   p‑MAP2K1/MEK1↓, 1,   MAPK↓, 4,   MAPK↑, 1,   p‑MAPK↓, 1,   mTOR↓, 3,   PI3K↓, 7,   p‑PI3K↓, 2,   PKCδ↓, 1,   PTEN↓, 1,   RAS↓, 1,   p‑Src↓, 1,   STAT3↓, 3,   p‑STAT3↓, 1,   p‑STAT6↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

ATF2↓, 1,   ATF4↑, 1,   cMyc↓, 3,   p‑cMyc↑, 1,   FOXO1↓, 1,   FOXO3↑, 1,   H3↓, 1,   H4↓, 1,   HDAC↓, 1,   HES1↓, 2,   miR-107↑, 2,   miR-139-5p↑, 2,   miR-155↓, 2,   miR-21↓, 2,   miR-224↓, 2,   miR-340↓, 2,   miR-34a↑, 2,   miR-34b-5p↑, 1,   miR-384↑, 2,   miR-422a↑, 2,   tumCV↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   eIF2α↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 2,   HSP90↓, 1,   PERK↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1/ATG6↑, 4,   LC3B-II↑, 1,   LC3II↑, 3,   TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   DNArepair↓, 1,   ERCC3↑, 1,   hTERT/TERT↓, 4,   P53↑, 4,   PARP↑, 1,   cl‑PARP↑, 2,   PCNA↓, 1,   Telomerase↓, 3,   TOP1↓, 1,   TOP2↓, 1,   XRCC1↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 5,   CDK4↓, 1,   p‑CHK1↑, 1,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 3,   cycD1/CCND1↓, 1,   Ki-67↓, 1,   P21↓, 1,   P21↑, 3,   p27/CDKN1B↑, 2,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CD34↓, 1,   cFos↑, 1,   IGF-1↓, 1,   IGF-2↓, 1,   Ki-67↓, 1,   NICD↓, 1,   NOTCH↓, 4,   NOTCH1↓, 3,   TAZ↓, 1,   TumCP?, 1,   TumCP↓, 6,   Wnt↓, 3,  

Migration(tgid=13) ⓘ

AEG1↓, 1,   AP-1↓, 1,   AXL↓, 1,   Ca+2↑, 2,   Cdc42↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 4,   EMT↓, 7,   FAK↓, 3,   ITGB1↓, 1,   MET↓, 1,   p‑MET↓, 1,   MMP1↓, 1,   MMP16↓, 3,   MMP2↓, 7,   MMP3↓, 3,   MMP9↓, 7,   MMPs↓, 1,   N-cadherin↓, 6,   PDGF↓, 1,   Rac1↓, 1,   Rho↓, 1,   Snail↓, 2,   TIMP1↑, 1,   TIMP2↑, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumMeta↓, 3,   Twist↓, 2,   Tyro3↓, 1,   Vim↓, 4,   Vim↑, 1,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 6,   Hif1a↓, 3,   VEGF↓, 6,   VEGFR1↓, 1,   VEGFR2/KDR/Flk1↓, 2,  

Barriers & Transport(tgid=15) ⓘ

CLDN1↓, 1,   MMP↓, 2,   ZO-1↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   CXCL16↓, 1,   CXCR4↓, 1,   HMGB1↓, 1,   ICAM-1↓, 1,   IFN-γ↓, 1,   IL1↓, 1,   IL2↑, 1,   IL6↓, 3,   Imm↝, 1,   NF-kB↓, 12,   p‑NF-kB↑, 1,   NLRP3↓, 1,   p‑p65↓, 1,   PD-1↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission(tgid=18) ⓘ

PTN↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

AR↓, 3,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   BioAv↝, 1,   ChemoSen↓, 1,   ChemoSen↑, 5,   CYP1A1↓, 2,   CYP1A2↓, 1,   Dose↝, 1,   eff↓, 1,   Half-Life↝, 1,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 2,   Synergy↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

AR↓, 3,   CEA↓, 1,   EGFR↓, 1,   EGFR↑, 1,   p‑EGFR↓, 1,   hTERT/TERT↓, 4,   IL6↓, 3,   NSE↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   cachexia↓, 1,   cardioP↑, 1,   chemoP↑, 2,   TumVol∅, 1,   TumW∅, 1,  

Infection & Microbiome(tgid=24) ⓘ

GutMicro↑, 1,  
Total Targets: 251

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 7,   ARE↑, 1,   Catalase↓, 1,   Catalase↑, 3,   GPx↑, 1,   GSH↑, 4,   GSR↑, 2,   GSTs↓, 1,   GSTs↑, 2,   HO-1↑, 2,   lipid-P↓, 3,   MDA↓, 1,   NQO1↑, 1,   NRF2↑, 5,   ROS↓, 8,   SOD↓, 1,   SOD↑, 6,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   AMPK↑, 1,   ATP↑, 1,   GSK‐3β↓, 1,   LDHA↑, 1,   SIRT1↑, 1,   SREBP1/SREBF1↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 1,   BAX↓, 1,   Bax:Bcl2↓, 1,   Casp1↓, 1,   Casp3↓, 3,   Casp9↓, 1,   Casp9↑, 1,   iNOS↓, 1,   p‑p38↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 1,   Akt↑, 1,   CREB↑, 1,   p‑JNK↓, 2,   p‑MKK4↑, 1,   mTOR↑, 1,   p‑mTOR↓, 1,   PI3K↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

ATF4↓, 1,   HDAC2↓, 1,   other↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 1,   ER Stress↓, 1,   GRP78/BiP↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1/ATG6↓, 2,  

Migration(tgid=13) ⓘ

AP-1↓, 1,   MMP1↓, 1,   TregCell↑, 1,   TXNIP↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 2,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 3,   MMP↑, 3,   ZO-1↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

AIF1/Iba-1↓, 1,   COX2/PTGS2↓, 3,   IFN-γ↓, 1,   IL10↑, 1,   IL18↓, 1,   IL1β↓, 4,   IL2↓, 1,   IL33↓, 1,   IL6↓, 3,   IL8↓, 1,   Inflam↓, 6,   pol-M2 MC↑, 1,   NeuroI↓, 1,   NF-kB↓, 5,   p‑NF-kB↓, 1,   NLRP3↓, 1,   TLR4↓, 1,   TNF-α↓, 3,  

Cellular Microenvironment(tgid=17) ⓘ

GFAP↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 2,   BDNF↑, 4,   PSD95↑, 1,   SNAP25↑, 1,   TrkB↑, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 2,   Aβ42↓, 1,   BACE/β-secretase↓, 2,   tau↓, 1,   p‑tau↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

PPARα↑, 1,   PPARγ↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 4,   BioAv↑, 1,   BioAv↝, 1,   eff↑, 1,   GSTA1↑, 1,   Half-Life↝, 1,   Synergy↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   BloodF↑, 1,   IL6↓, 3,  

Functional Outcomes(tgid=23) ⓘ

antiAll↑, 1,   cognitive↑, 4,   hepatoP↑, 1,   Learn↑, 1,   memory↑, 2,   motorD↑, 1,   Mucositis↓, 1,   neuroP↑, 6,   toxicity↓, 2,  

Infection & Microbiome(tgid=24) ⓘ

GutMicro↑, 1,  
Total Targets: 110

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B
17 Luteolin
1 Quercetin
1 Apigenin (mainly Parsley)
1 Baicalein
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:118  Target#:214  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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