Luteolin 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↓, 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↓, ITG">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.


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
SREBP2↓, ecreased transcription of SREBP-2 upon the apigenin treatment
eff↑, 25 lM of both flavones could significantly bring down the induced pMEK and pERK.
p‑MEK↓,
p‑ERK↓,

7815- Api,  LT,  NarG,  QC,  MOR  The role of natural flavonoids on neuroinflammation as a therapeutic target for Alzheimer’s disease: a narrative review
- Review, AD, NA
*NeuroI↓, 13 natural flavonoids (apigenin, luteolin, naringenin, quercetin, morin, kaempferol, fisetin, isoquercitrin, astragalin, rutin, icariin, mangiferin, and anthocyanin) derived from plants or medicinal herbs on neuroinflammation in Alzheimer’s diseas

2596- Api,  LT,    Natural Nrf2 Inhibitors: A Review of Their Potential for Cancer Treatment
- Review, Var, NA
NRF2↓, In addition, natural compounds such as apigenin, luteolin, chrysin and brusatol have been shown to be potent Nrf2 inhibitors.
chemoPv↑, 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.
ChemoSen↑,

2625- Ba,  LT,    Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocyte
- in-vivo, Stroke, NA
*lipid-P↓, Baicalein and luteolin prevented the Fe-SP-induced lipid peroxidation in rat neonatal cardiomyocytes.
*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.
*NRF2∅, Our results suggest that BAI and Lut prevented the I/R-induced increased of ACSL4, NRF2, and HO-1 protein
*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
*Ferroptosis↓, BAI was found to suppress ferroptosis in cancer cells via reducing reactive oxygen species (ROS) generation.
*ROS↓,
*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
*eff↑, BAI and Lut reduced the I/R-induced myocardium infarction
*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,  Cro,  QC,    Naturally Occurring Acetylcholinesterase Inhibitors and Their Potential Use for Alzheimer's Disease Therapy
- Review, AD, NA
*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.
*AChE↓, Fig1: Berberine(1uM), Luteolin(80uM), Crocetin(100uM), Quercetin(120uM)

8099- KAE,  LT,  CHr,    Kaempherol and Luteolin Decrease Claudin-2 Expression Mediated by Inhibition of STAT3 in Lung Adenocarcinoma A549 Cells
- in-vitro, Lung, A549
CLDN2↓, flavonoids including kaempferol, chrysin, and luteolin concentration-dependently decrease claudin-2 expression in lung adenocarcinoma A549 cells.
TumCP↓, The inhibition of cell proliferation caused by kaempferol and luteolin
STAT3↓, kaempferol and luteolin decreased claudin-2 expression and proliferation in A549 cells mediated by the inhibition of binding of STAT3

8370- LT,    Luteolin Induces GPX4-dependent Ferroptosis and Enhances Immune Activation in Colon Cancer
- vitro+vivo, Colon, NA
TumCP↓, Luteolin dose-dependently inhibited colon cancer cell proliferation
ROS↑, Luteolin triggered ROS/Fe2+ accumulation, lipid peroxidation, MDA elevation, GSH depletion, and GPX4 downregulation.
Iron↑,
lipid-P↑,
MDA↑,
GSH↓,
GPx4↓,
Ferroptosis↑, In vivo, luteolin exhibited antitumor efficacy through GPX4 downregulation and ferroptosis induction, synergistically promoting intratumoral M1 macrophage polarization and CD8+ T lymphocyte activation.
pol-M1↑,
CD8+↑,
Imm↑, promotes antitumor immune responses.

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

8371- LT,    Study on the regulatory mechanism of luteolin inhibiting WDR72 on the proliferation and metastasis of non small cell lung cancer
- vitro+vivo, Lung, A549 - in-vitro, Lung, H1299 - in-vitro, Nor, BEAS-2B
TumCP↓, Luteolin significantly inhibited the proliferation, invasion, and migration of NSCLC cell lines (H1299 and A549) and reduced tumor formation in nude mice.
TumCI↓,
TumCMig↓,
TumVol↓,
p‑Akt↓, Luteolin treatment in WDR72-overexpressing cells resulted in decreased phosphorylated AKT, increased apoptosis, and suppressed EMT.
Apoptosis↓,
EMT↓,
Dose↝, nude mice following intraperitoneal luteolin injections (50 mg/kg) every other day for two weeks revealed no significant histological damage
Akt↓, Luteolin inhibits EMT, AKT and promotes apoptosis in non-small cell lung cancer cells by inhibiting the expression of WDR72
WDR72↓,
TumMeta↓, while luteolin, by inhibiting WDR72, can suppress the proliferation and metastasis of non-small cell lung cancer cells.

8372- LT,    Luteolin targets peroxiredoxin 2 to augment T-cell-mediated cytotoxicity and suppress lung adenocarcinoma progression
- in-vitro, Lung, NA
TumCP↓, luteolin significantly inhibits the proliferation and migration of LUAD cells.
Apoptosis↑, luteolin promotes apoptosis of lung cancer cells by enhancing T-cell-mediated killing pathways via PRDX2.
PrxII↓, luteolin binds to PRDX2, inhibiting the JAK2/STAT3 pathway, suppressing PD-L1 expression, promoting the release of perforin and granzyme B from CD8+ T cells, and inhibiting immune evasion in LUAD, thereby inhibiting the progression of lung adenocarci
JAK2↓,
STAT3↓,
PD-L1↓,
Perforin↑,
GranB/GZMB↑,

8373- LT,  ATV,    Evaluation of Luteolin Nanosuspensions on Pharmacokinetics of Atorvastatin: Drug-Drug Interactions Using Rat Models
- in-vivo, Nor, NA
*OATPs↓, LUT nanosuspensions could significantly increase systemic exposure to ATV by inhibiting CYP450s and OATPs activities
*cytoP450↓,

8374- LT,  NarG,    Interaction of luteolin, naringenin, and their sulfate and glucuronide conjugates with human serum albumin, cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) enzymes and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters
- in-vitro, Nor, NA
*OATPs↓, Certain conjugates of luteolin and naringenin are potent inhibitors of OATP1B1 and/or OATP2B1 enzymes.

8375- LT,    Luteolin, a flavone ingredient: Anticancer mechanisms, combined medication strategy, pharmacokinetics, clinical trials, and pharmaceutical researches
- Review, Var, NA
TumCP↓, luteolin executes multiple anticancer effects mainly by dampening proliferation and invasion, spurring apoptosis, intercepting cell cycle, regulating autophagy and immune, inhibiting inflammatory response, inducing ferroptosis, and pyroptosis
TumCI↓,
Apoptosis↑,
TumCCA↑,
Inflam↓,
Ferroptosis↑,
Pyro↑,
ChemoSen↑, Luteolin can be applied in combination with numerous clinical anticarcinogens and natural ingredients to synergistically enhance the therapeutic efficacy of malignancies while reducing adverse reactions.
chemoP↑,
*BioAv↓, luteolin has an unfavorable oral bioavailability, it mainly persists in plasma as glucuronides and sulfate-conjugates after being metabolized,
OATPs↓, regarded as potent inhibitors of OATP1B1 and OATP2B1

8376- LT,  Cisplatin,    Luteolin sensitizes the anticancer effect of cisplatin via c-Jun NH2-terminal kinase-mediated p53 phosphorylation and stabilization
- vitro+vivo, Var, NA
ChemoSen↑, sensitization effect of luteolin on cisplatin-induced apoptosis is p53 dependent, as such effect is only found in p53 wild-type cancer cells but not in p53 mutant cancer cells.
JNK↑, luteolin activates JNK, and JNK then stabilizes p53 via phosphorylation, leading to reduced ubiquitination and proteasomal degradation.
P53↑, in vivo nude mice xenograft model, we confirmed that luteolin enhanced the cancer therapeutic activity of cisplatin via p53 stabilization and accumulation.

8377- LT,    Luteolin: exploring its therapeutic potential and molecular mechanisms in pulmonary diseases
- Review, Asthma, NA
*PI3K↑, multiple molecular mechanisms; these include inhibition of activation of the PI3K/Akt-mediated Nuclear Factor kappa-B (NF-κB) and MAPK signaling pathways, as well as the promotion of regulatory T cell (Treg)
*Akt↑,
*Inflam↓, alleviating inflammation and oxidative stress response
*ROS↓,
*BioAv↓, Luteolin, a naturally occurring polyphenol, is poorly water-soluble. The oral route may be ineffective because the gut poorly absorbs this type of flavonoid.
*RenoP↑, renoprotective (Diniz et al., 2022; Oyagbemi et al., 2021; Xiong et al., 2020), cardioprotective (Liu Z. et al., 2022; Xu et al., 2012) and neuroprotective (Nabavi et al., 2015; Ashaari et al., 2018) properties.
*cardioP↑,
*neuroP↑,
*antiAll↑, anti-allergic (Liang et al., 2020), anti-diabetic (Pradhan and Kulkarni, 2024),
*AntiDiabetic↑,
*hepatoP↑, hepatoprotective (Yao et al., 2023) and antithrombotic (Choi et al., 2015)
*AntiThr↑,
*toxicity↓, Numerous studies have indicated that the toxicity of luteolin is minimal, showing no significant harmful effects in clinical trials
*IL10↓, anti-inflammatory effects of luteolin are associated with reduced IL-10 levels.
*Sepsis↓, Luteolin protects lung tissue from SALI and reduces the excessive accumulation of IL-10 in the lungs during sepsis
*TNF-α↓, Celebi and colleagues found that luteolin mainly reduces the expression of TNF-α mRNA, decreases oxidative stress,
*ROS↓,
*GSH↑, An increase in malondialdehyde (MDA) caused by free radicals formed during sepsis was normalized by luteolin treatment, which improved glutathione (GSH) levels, CAT, and superoxide dismutase (SOD) activity, and reduced MDA levels
*Catalase↑,
*SOD↑,
*MDA↓,
*lipid-P↓, counteracting lipid peroxidation.
*IL4↓, decreased the levels of interleukin-4 (IL-4) and interleukin-5 (IL-5) in the BALF, attenuating the asthmatic characteristics of the experimental mice
*IL5↓,
*PGE2↓, inhibiting the production of Prostaglandin E2 (PGE2) (Jin et al., 2009).
*PI3K↑, luteolin activated the PI3K/Akt/mTOR pathway in the lung tissues of asthmatic mice and inhibited the Beclin-1-PI3KC3 protein complex.
*Akt↑,
*mTOR↑,
*Beclin-1/ATG6↓,
*Mucositis↓, suppressing excessive mucus secretion.
*PLA2↓, Figure6
STAT3↓, Luteolin inhibits the STAT3 signaling pathway and the expression of PD-L1, thereby exposing tumor cells to T cells of the immune system (
PD-L1↓,
miR-34a↓, luteolin upregulates the expression of miR-34a, which may subsequently inhibit the proliferation of non-small cell lung cancer (NSCLC)
Casp3↑, activation of caspase-9 and caspase-3, decreases the expression of Bcl-2, increases the expression of BAX, increases the BAX/Bcl-2 ratio, and induces apoptosis
Casp9↑,
Bcl-2↓,
BAX↑,
Bax:Bcl2↑,
Apoptosis↑,
ROS↑, accumulation of ROS induced by luteolin
EMT↓, Luteolin has been demonstrated to inhibit EMT and downregulate E-cadheri
E-cadherin↓,
DR5↑, By increasing DR5 expression and Drp1-mediated mitochondrial fission, luteolin enhances the sensitivity of NSCLC cells to TRAIL
LIMK1↓, suppresses tumor growth by inhibiting LIMK1 activity
Pain↓, luteolin also possesses the ability to alleviate bone cancer pain

8378- LT,    Luteolin and its derivatives: modulation of epithelial-mesenchymal transition in fibrosis and cancer
- Review, Var, NA
EMT↓, Luteolin inhibits EMT via multi-target regulation of core pathways (TGF-β1/Smad, PI3K/Akt, Hippo/YAP), exerting consistent dose-dependent efficacy in suppressing cancer metastasis
TGF-β1↓, downregulates TGF-β1
Smad1↓,
PI3K↓, uteolin not only suppresses downstream Smad-dependent transcriptional responses but also attenuates key non-Smad signaling branches, including PI3K/Akt and MAPK pathways
Akt↓,
Hippo↝,
YAP/TEAD↓, This effectively suppresses YAP/TAZ-driven transcriptional programs that are activated by mechanical stress and growth factors,
*NRF2↑, luteolin could alleviate the pathological process driven by oxidative stress by activating the Nrf2/HO-1 antioxidant pathway, regulating AMPK energy sensing and inhibiting NADPH oxidase-derived reactive oxygen species
*HO-1↑,
*ROS↓,
E-cadherin↑, restores E-cadherin/ZO-1 (epithelial markers); suppresses N-cadherin, Vimentin, Claudin-1, β-catenin, Snail, TCF/ZEB1 (mesenchymal markers)
ZO-1↑,
Vim↓,
CLDN1↓,
β-catenin/ZEB1↓,
Snail↓,
TCF↓,
Zeb1↓,
angioG↓, 4. Inhibits angiogenesis,
eff↑, luteolin and its derivative apigenin enhance antitumor immunity in KRAS-mutant lung cancer by suppressing STAT3-mediated PD-L1 expression, thereby synergizing with PD-1 blockade
ROS↑, pca: Oxidative stress and apoptosis in mCRPC cells; cytotoxicity and pro-oxidant effects
mtDam↑, In gastric cancer, luteolin inhibits tumor progression primarily by inducing mitochondrial dysfunction and triggering the intrinsic apoptotic pathway—evidenced by loss of mitochondrial membrane potential and impaired electron transport chain activi
MMP↓,
ETC↓,

8379- LT,    Luteolin and neuroinflammation: a multi-target therapeutic strategy for central nervous system disorders
- Review, Var, NA - Review, AD, NA - Review, Stroke, NA
*neuroP↑, Luteolin, a natural flavonoid abundant in medicinal plants, fruits, and vegetables, exerts multifaceted neuroprotective effects across diverse experimental disease models.
*Inflam↓, attenuate inflammatory mediator release, reduce oxidative stress-induced neuronal damage, and inhibit apoptosis, thereby counteracting neuroinflammation-driven pathology
*ROS↓,
*Apoptosis↓,
*BioAv↓, notably limited oral bioavailability and restricted blood-brain barrier (BBB) permeability
*BBB∅,
Ferroptosis↑, In colon cancer, luteolin promotes ferroptosis in tumor cells by facilitating the accumulation of ROS/Fe2+, lipid peroxidation, elevated MDA, GSH depletion, and downregulation of GPX4.
ROS↑,
Iron↑,
lipid-P↑,
MDA↑,
GSH↓,
GPx4↓,
*Aβ↓, Similarly, combined treatment with luteolin and exercise reverses the increase in Aβ conten
*memory↑, reducing neuroinflammation and thereby slowing the progression of memory dysfunction in AD
*neuroG↑, Luteolin treatment promotes hippocampal neurogenesis, improves dendritic spine maturation and the dendritic arborization of hippocampal and cortical neurons
*NRF2↑, luteolin significantly enhances the expression of Nrf2 while concurrently downregulating NLRP3 inflammasome activation.
*NLRP3↓,
*ROS↓, This attenuates oxidative stress, inflammatory responses, and neuronal degeneration, exerting a protective effect by inhibiting the NLRP3 inflammasome
JAK2↓, Research has found that in lung adenocarcinoma, luteolin binds to PRDX2, inhibiting the JAK2/STAT3 pathway, reducing PD-L1 expression, and promoting the release of perforin and granzyme B by CD8+ T cells.
STAT3↓,
PD-L1↓,
Perforin↝,
GranB/GZMB↝,
hepatoP↑, In esophageal cancer, combination therapy with luteolin and paclitaxel mitigates paclitaxel-induced hepatotoxicity,
*Learn↑, studies have demonstrated that in AD, luteolin treatment dose-dependently improves spatial learning and memory deficits in AD mouse models.
*TNF-α↓, (evidenced by reduced levels of TNF-α, IL-1β, IL-6, NO, COX-2, and iNOS protein)
*IL1β↓,
*IL6↓,
*NO↓,
*COX2/PTGS2↓,
*iNOS↓,
*ER Stress↓, luteolin decreases the expression of ER stress markers GRP78 and IRE1α in brain tissue.
*GRP78/BiP↓,
*IRE1↓,
*cognitive↑, thereby contributing to cognitive improvement
*BAX↓, Bax, Bcl-2, Caspase-3, and Cox-2 is significantly diminished, while the expression of synaptic markers like PSD-95 and SNAP-25 is markedly increased.
*Bcl-2↓,
*Casp3↓,
*PSD95↑,
*SNAP25↑,
*JNK↓, luteolin may attenuate Aβ-related neuroinflammation and neurodegeneration, potentially through the inhibition of JNK signaling
*eff↑, Combinatorial therapy with DHA, luteolin, and UA has shown enhanced efficacy in inhibiting Aβ pathology
*mtDam↓, By reversing mitochondrial swelling and restoring mitochondrial transmembrane potential, it augments antioxidant capacity and exerts neuroprotective effects following cerebral ischemia
*MMP↑,
*Stroke↓,
*TJ↑, Luteolin also inhibited the degradation of tight junction proteins and decreased MMP9 expression, thereby ameliorating BBB permeability
*MMP9↓,
*BBB∅,
*NeuroI↓, luteolin may provide neuroprotection following cerebral ischemia-reperfusion injury by inhibiting neuroinflammation and oxidative stress.

8369- LT,    Luteolin inhibits proliferation of lung cancer A549 cells by increasing ROS production and inhibiting the AKT/mTOR signaling pathway and HO-1 expression
- in-vitro, Lung, A549
tumCV↓, luteolin dose-dependently inhibited the viability and proliferation of A549 cells, increased intracellular ROS levels, up-regulated the expressions of Bax, cleaved caspase-9, and Beclin 1
TumCP↓,
ROS↑,
BAX↑,
cl‑Casp9↑,
Beclin-1/ATG6↑,
LC3B-II↑, increased the LC3B-II/LC3B-I ratio, down-regulated the expressions of Bcl-2 and P62, and induced cell apoptosis and autophagy.
Bcl-2↓,
p62↓,
TumAuto↑,
p‑Akt↓, Luteolin also significantly inhibited the phosphorylation of AKT and mTOR and down-regulated the expression of HO-1 protein in the cells.
p‑mTOR↓,
HO-1↓,

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↓,

8367- LT,    Role of Luteolin in Prevention of Oral, Esophageal, Gastric, Pancreatic, and Colon Cancers: Recent Trends and Future Perspectives
- Review, Var, NA
*antiOx↑, The multifaceted protective mechanism/s offered by luteolin are contributed by its antioxidative, anti-inflammatory, and anti-proliferative properties, thus characterizing it as a potent drug candidate against gastrointestinal cancers.
ROS↓, Particularly, the impact of luteolin on limiting esophageal and gastric cancers is mediated by alleviating oxidative stress, inhibiting chronic inflammation, and significant induction of apoptosis
Inflam↓,
Apoptosis↑,

8366- LT,    Preliminary Evidence on Safety and Clinical Efficacy of Luteolin for Patients With Prostate Cancer Under Active Surveillance
- Trial, Pca, NA
Dose↝, five patients with low–intermediate risk PCA and under AS were treated daily with 50 mg of oral luteolin for six months.
eff↑, Our small phase I study of men with PCA suggests that daily treatment with 50 mg of an oral supplement of luteolin is safe and effective with regard to oncological outcomes, particularly in patients under AS
SD↑, two patients showed a favorable response, one patient had stable disease, and two patients showed disease progression; robot-assisted radical surgery was subsequently performed for the latter.
Ki-67↓, Ki67 expression in the SD patient tended to decrease after treatment
AR↓, may suppress PCA progression in patients under AS via the attenuation of expression of AR and NKX3.1
NKX3.1↓,
miR-29b↑, miR-29 and miR-30 induced by luteolin have important roles in reducing AR and NKX3.1 levels, resulting in inhibiting PCA progression.
miR-30a-5p↑,

7825- LT,  MBS,    Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer's Disease: A Review
- Review, AD, NA
*neuroP↑, neuroprotective activity of luteolin was also observed in a transgenic Drosophila model.
*OS↑, showed that luteolin extend the life span of Drosophila, enhanced its antioxidative ability, and directly bound to Aβ42 and AChE to inhibit the Aβ aggregation and cholinergic deficits
*antiOx↑,
*Aβ42↓,
*AChE↓,
*Aβ↓,
*IRes↓, It was found that luteolin (50 mg/kg) reduced cerebral insulin resistance and tau hyperphosphorylation in a high fat diet (HFD
*p‑tau↓,
*ROS↓, neuroprotective activity in AD was achieved by inhibition of oxidative stress, apoptosis, neuroinflammation, AChE activity, cerebral insulin resistance, or iron imbalance.
*Apoptosis↓,
*Inflam↓,
*Iron↝,

4883- LT,  CHr,  BRU,  VitC,    An update of Nrf2 activators and inhibitors in cancer prevention/promotion
- Review, Var, NA
*NRF2↓, figure 3

4687- LT,  QC,    Dietary Flavonoids Luteolin and Quercetin Suppressed Cancer Stem Cell Properties and Metastatic Potential of Isolated Prostate Cancer Cells
- in-vitro, Pca, DU145
CSCs↓, Since luteolin and quercetin were able to target CSC cells and prevent cancer cell invasiveness, may serve as potential anti-angiogenesis and anti-metastasis agents.
EMT↓, Furthermore, reversed epithelial-mesenchymal transition (EMT) to reduce MMP secretion by Lu and Qu exert inhibition of migration and invasion abilities in A431 cells
MMPs↓,
TumCMig↓,
TumCI↓,

4339- LT,    Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis
- in-vivo, Nor, NA
*AntiAg↑, Luteolin inhibits platelet activation and thrombus formation
*ROS↓, Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity.

4338- LT,    Luteolin: a natural product with multiple mechanisms for atherosclerosis
- Review, Var, NA
*Inflam↓, Figure 2
*ROS↓,
*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.
*lipid-P↓, luteolin prevents aortic lipid accumulation and atherosclerotic plaque formation in LDLR −/− mice induced by a Western diet.
*AMPK↑, luteolin prevents aortic lipid accumulation and atherosclerotic plaque formation in LDLR −/− mice induced by a Western diet.
*SIRT1↑,
*AntiAg↑,

4295- LT,    Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury
- in-vivo, AD, NA
*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
*GSK‐3β↓,
*p‑tau↓,
*BBB↑, we determined the ability of peripherally administered luteolin to cross the blood brain barrier (BBB).

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

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,

8406- LT,  Cisplatin,    Luteolin sensitizes the anticancer effect of cisplatin via c-Jun NH2-terminal kinase–mediated p53 phosphorylation and stabilization
- vitro+vivo, Liver, HepG2 - in-vitro, Laryn, HEp2
ChemoSen↑, anticancer effect of luteolin and support its potential clinical application as a chemosensitizer in cancer therapy
Dose↝, cells were pretreated with luteolin for 2 h (40 μmol/L for HCT116 and CNE-1 and 20 μmol/L for HepG2) and then treated with indicated concentrations of cisplatin (μg/mL) for another 24 h.
P53↑, Significant increase of p53 protein level was observed as early as 3 h after luteolin treatment,

8405- LT,  Rad,    Luteolin's role as a radiosensitizer by promoting cell death and ROS modulation
- Review, NSCLC, NA
RadioS↑, Taken together, we conclude that luteolin contain role of radiosensitizer via promotion of cell death and ROS accumulation.
ROS↑,

8403- LT,    Luteolin induces apoptotic cell death via antioxidant activity in human colon cancer cells
- in-vitro, CRC, HT-29
tumCV↓, Luteolin decreased cell viability in human colon cancer cells (HT-29), whereas it had no effect on normal colon cells (FHC).
selectivity↑,
Apoptosis↑, Luteolin induced apoptosis by activating the mitochondria-mediated caspase pathway in HT-29 cells
Casp↑,
MMP↓, Luteolin caused loss of the mitochondrial membrane action potential, increased mitochondrial Ca2+ level, upregulated Bax, downregulated Bcl-2, induced the release of cytochrome c from mitochondria to the cytosol
Ca+2↑,
BAX↑,
Bcl-2↓,
Cyt‑c↑,
Casp9↑, increased the levels of the active forms of caspase-9 and caspase-3
Casp3↑,
ROS↓, Luteolin-induced apoptosis was accompanied by the activation of intracellular and mitochondrial reactive oxygen species scavenging through the activation of antioxidant enzymes, such as superoxide dismutase and catalase in HT-29 cells.
SOD↑,
Catalase↑,
GSH↑, Luteolin increased the level of reduced glutathione (GSH) and the expression of GSH synthetase, which catalyzes the second step of GSH biosynthesis.
antiOx↑, luteolin induces apoptosis by promoting antioxidant activity and activating MAPK signaling in human colon cancer cells.
MAPK↑,

8402- LT,    Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway
- vitro+vivo, CRC, T24/HTB-9
tumCV↓, Luteolin inhibited cell survival and induced G2/M cell‐cycle arrest, p21 upregulation and downregulation of phospho(p)‐S6, which is downstream of mTOR signaling.
TumCCA↑,
p‑S6↓,
P21↑, Luteolin has a cancer suppressive effect and upregulates p21Waf1/Cip1 in bladder cancer cells
Trx1↑, Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production.
ROS↓,
Ki-67↓, significantly decreased the Ki67‐labeling index
mTOR↓, Luteolin inhibits the mechanistic target of rapamycin pathway in bladder cancer
TumCP↓, The upregulation of TRX1 by luteolin suppresses cell proliferation in bladder cancer cells

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

8400- LT,    Luteolin inhibits triple-negative breast cancer by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling
- in-vitro, BC, NA
TumCP↓, Luteolin dramatically suppressed cell proliferation, invasion, and migration while favoring cell apoptosis in a dose- and time-dependent manner.
TumCI↓,
TumCMig↓,
Apoptosis↑,
SGK1↓, In TNBC cells treated with luteolin, SGK1 and AKT3 were significantly downregulated while their downstream gene BNIP3 was upregulated.
AKT3↓,
BNIP3↑,

8399- LT,    Protective effects of luteolin against amyloid beta-induced oxidative stress and mitochondrial impairments through peroxisome proliferator-activated receptor γ-dependent mechanism in Alzheimer's disease
- in-vivo, AD, NA
*memory↑, Our study showed that luteolin supplement significantly ameliorated memory and cognitive impairment of AD mice and exerted neuroprotection by inhibiting Aβ generation, repairing mitochondrial damage and reducing neuronal apoptosis
*cognitive↑,
*neuroP↑,
*Aβ↓,
*mtDam↓,
*Apoptosis↓,
*PPARγ↑, Further research revealed that luteolin could directly bind with peroxisome proliferator-activated receptor gama (PPARγ) to promote its expression and function.
*ROS↓, inhibited Aβ-induced oxidative stress
*SOD↑, Luteolin treatment remarkably grew both SOD activity and GSH level, but stopped the level of MDA.
*GSH↑,
*NRF2↑, while luteolin treatment obviously increased the intensity of NRF2 in the CA1 region.
*MFN2↑, After treatment of luteolin, the mitochondrial dynamics was recovered, evidenced by the increased Mfn2 level and decreased Drp1 and Fis1 levels in primary neurons
*DRP1/DNM1L↓,
*FIS1↓,
*Bcl-2↑, luteolin treatment effectively increased the bcl-2 expression levels and decreased Bax, CytC, cleaved-caspase9 and cleaved-caspase3 expression levels.
*BAX↓,
*Cyt‑c↓,
*cl‑Casp9↓,
*cl‑Casp3↓,
*IDE↑, luteolin-induced increase of IDE level and the decreases of BACE1 and Aβ1-42 levels, but did not affect the expression of APP.
*BACE/β-secretase↓,
*Aβ42↓,

8398- LT,    Luteolin: Nature's promising warrior against Alzheimer's and Parkinson's disease
- Review, AD, NA - Review, Park, NA
*antiOx↑, Luteolin is a flavone that possesses potent antioxidant and anti-inflammatory properties.
*Inflam↓,
*AntiBio↑, Luteolin has antiinflammatory, antimicrobial, antioxidant, anticancer, antiulcer, antiinfluenza, cytoprotective, hepatoprotective, neuroprotective, cardioprotective, neurogenesis, and neurotrophic activity, macrophage polarization, and detoxifying fr
*AntiCan↑,
*hepatoP↑,
*neuroP↑,
*cardioP↑,
*neuroG↑,
*BBB↑, In addition, luteolin can pass the blood–brain barrier and employ its neuroprotective effects.
*ROS↓, Luteolin decreases oxidative stress, suppresses inflammation, microglia activation, neurotoxicity, acetylcholinesterase (AChE), and tau phosphorylation, prevents the production of β‐amyloid plaques
*AChE↓,
*p‑T-cadherin↓,
*Aβ↓,
*memory↑, improves memory.
*TNF-α↓, inhibiting the release of pro‐inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL)‐1β, as well as chemokines like CCL2 and CCL5 from human mast cells.
*IL1β↓,
*MCP1/CCL2↓,
*RANTES↓,
*BioAv↑, a recent study looked at how much luteolin is bioavailable in peanut hull extract (PHE). maximum concentration of luteolin in plasma reached 8.34 ± 0.98 μg/mL for PHE and 1.97 ± 0.15 μg/mL for luteolin.
*Half-Life↝, The time to attain the maximal plasma concentration was 0.520 ± 0.05 h for PHE and 1.02 ± 0.22 h for luteolin. Furthermore, the luteolin half‐life (t1/2) was 4.94 ± 1.2 h while the PHE t1/ 2 was 2.772 ± 0.54 h.
*toxicity↓, Luteolin is generally considered safe and lacks recognized toxicity
*BACE/β-secretase↓, Markers such as (BACE1), (Aβ1–42), Cox‐2, Bcl‐2, Caspase‐3, and Bax, were drastically decreased
*Aβ42↓,
*COX2/PTGS2↓,
*Bcl-2↓,
*Casp3↓,
*BAX↓,
*GSTs↓, reduced GST, LPO, AChE, PCC, CAT, caspase 3, and caspase 9 activity, reduced Aβ42 peptides expression
*lipid-P↓,
*Casp3↓,
*Casp9↓,
*memory↑, improved memory impairment and halted CA1 pyramidal cell layer shrinkage
*GSK‐3β↓, decreased levels of GSK‐3 activation, β‐amyloid deposition, pro‐inflammatory cytokines, and phosphorylated tau
*ChAT↑, increased activity of ChAT, SOD, GSH‐Px, inhibited oxidative injuries, enhanced activity of AchE was reversed and increased Ach content while MDA reduced
*SOD↑,
*GPx↑,
*MDA↓,
*ER Stress↓, decrease in the expression of estrogen receptor (ER) stress markers, including GRP78 and inositol‐requiring transmembrane kinase/ endoribonuclease 1α, in brain tissues.[
*GRP78/BiP↓,
*NRF2↑, figure 3
*motorD↑, improved motor asymmetry and motor impairment
*antiAll↑, Luteolin has also demonstrated antiallergic efficacy both in vitro as well as in vivo via several mechanisms, involving the release of histamine suppression.

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

8396- LT,  Myr,  KAE,  QC,  Api  Antiplatelet Effects of Flavonoid Aglycones Are Mediated by Activation of Cyclic Nucleotide-Dependent Protein Kinases
- in-vivo, Nor, NA
*other↝, six flavonoid aglycones (luteolin, myricetin, quercetin, eriodictyol, kaempferol, and apigenin) on platelet activation, phosphatidylserine externalization, formation of reactive oxygen species, and intracellular esterase activity.
*AntiAg↑, We found that these compounds significantly inhibit thrombin-induced platelet activation and decrease formation of reactive oxygen species in activated platelets.
*ROS↓,

8395- LT,  PacT,    Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma
- in-vitro, ESCC, NA
*AntiTum↑, Luteolin is a natural flavonoid with strong anti-tumor effects.
TumCP↓, luteolin inhibited tumor resistance (inhibited proliferation, induced cell cycle arrest and apoptosis and hindered migration invasion, EMT and stem cell spherification) in vitro in PTX-resistant esophageal squamous cell carcinoma (ESCC) cells.
TumCCA↑,
Apoptosis↑,
TumCMig↓,
EMT↓,
ChemoSen↑, luteolin enhanced drug sensitivity and promoted the apoptosis of drug-resistant ESCC cells in combination with PTX.
PI3K↓, Mechanistically, luteolin may inhibit the PI3K/AKT
Akt↓,
FAK↓, downregulating the FAK/PI3K/AKT pathway in PTX-resistant ESCC

8394- LT,    Luteolin prevents THP-1 macrophage pyroptosis by suppressing ROS production via Nrf2 activation
- in-vitro, Nor, NA
*Pyro↓, The results showed that luteolin exhibited a potent preventive effect on THP-1 macrophage pyroptosis
*NLRP3↓, luteolin was found to significantly reduce the expression of NLRP3, pro-CASP-1 and CASP-1,
*proCasp1↓,
*Casp1↓,
*NRF2↑, luteolin promoted Nrf2 nuclear translocation, thereby increasing the expression of HO-1 that reduces ROS production,
*HO-1↑,
*ROS↓,

8380- LT,    Luteolin, a bioactive compound from Celastrus orbiculatus stem, inhibits cervical cancer via CA2 suppression: A translational study bridging basic research and clinical application
- Trial, Cerv, NA
Dose↝, Luteolin was identified as a major constituent of the extract.
Ca+2↓, inhibits cervical cancer via CA2 suppression

8392- LT,    Revisiting Luteolin Against the Mediators of Human Metastatic Colorectal Carcinoma: A Biomolecular Approach
- in-vitro, CRC, HCT15 - in-vitro, CRC, HCT116 - in-vitro, CRC, DLD1 - in-vitro, CRC, HT-29 - in-vitro, Nor, RWPE-1
selectivity↑, luteolin was found to be effective against the different mCRC cell lines (HCT-15, HCT-116, DLD-1, and HT-29) without hampering the viability of non-tumorigenic ones (RWPE-1).
β-catenin/ZEB1↓, luteolin was found to inhibit β-catenin activity (a key regulator of mCRC) through direct physical interactions
GSK‐3β↑, by activating GSK3-β and ceasing its activation by inactivating AKT1 and PI3K-α.
AKT1↓,
PI3K↓,
p50↓, Luteolin also inhibited p50 activity, which could be useful in mitigating mCRC-associated proinflammatory milieu.

8391- LT,    Mechanism of luteolin against non-small-cell lung cancer: a study based on network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experiments
- in-vitro, NSCLC, NA
other↝, Six core targets, TP53, EGFR, AKT1, TNF, JUN, and CASP3, were screened via the PPI network
TumCP↓, in vitro, luteolin significantly inhibited the proliferation and migration of A549 cells, while also inducing apoptosis.
TumCMig↓,
Apoptosis↑,
p‑Akt↓, luteolin downregulated the expression of p-Akt (Ser473), MDM2, and Bcl-2 but upregulated the expression of p53 and Bax
MDM2↓,
Bcl-2↓,
P53↑,
BAX↑,

8390- LT,    Luteolin in Inflammatory Bowel Disease and Colorectal Cancer: A Disease Continuum Perspective
- Review, IBD, NA - Review, CRC, NA
*Diff↝, luteolin regulates immune cell differentiation, mitigates inflammation and oxidative stress, modulates gut microbiota, and restores intestinal mucosal barrier function in IBD.
*Inflam↓,
*ROS↓, Reduction in the Inflammatory Response and Reactive Oxygen Species (ROS)
*GutMicro↑,
*IBI↑,
TumCP↓, In the context of CRC, luteolin demonstrates significant anti-tumor effects by inhibiting cancer cell proliferation, inducing apoptosis, and suppressing cell migration and invasion.
Apoptosis↑,
TumCMig↓,
TumCI↓,
*BioAv↑, such as the use of polymer micelles and responsive nanoparticles, have greatly improved the bioavailability and efficacy of luteolin.
*iNOS↓, It effectively mitigates the inflammatory response by decreasing the expression of inflammatory mediators such as inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6).
*TNF-α↓,
*IL6↓,
*MDA↓, luteolin lowered colonic dialdehyde (MDA) levels, a biomarker of lipid peroxidation, indicating its antioxidant effects
*lipid-P↓,
*antiOx↑,
*NRF2↑, The antioxidant properties of luteolin are associated with its activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.
*HO-1↑, This pathway activation enhances the expression of antioxidant enzymes, including heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1), which are crucial for maintaining intracellular redox balance
*NQO1↑,
*SOD↑, Luteolin treatment also increased the activities of colonic superoxide dismutase (SOD) and catalase (CAT), key components of the cellular antioxidant defense system that help mitigate oxidative stress damage
*Catalase↑,
*5HT↓, Luteolin reduced the generation of 5-HT by inhibiting TPH-1 expression and the MAPK/ERK signaling pathway, thus producing an inhibitory effect on intestinal inflammation
*TPH1↓,
*MAPK↓,
*ERK↓,
*Inflam↓,
cycD1/CCND1↓, luteolin downregulates the expression of Cyclin D1 and CDK4, blocking the transition of CRC cells from the G1 phase to the S phase, thereby reducing cell proliferation
CDK4↓,
TumCCA↑,
Casp3↑, luteolin activates Caspase-3 and Caspase-9, triggering the mitochondrial pathway to promote cell death.
Casp9↑,
PI3K↓, luteolin inhibits the activation of the PI3K/Akt signaling pathway, reducing the phosphorylation of Akt and mTOR, thus inhibiting CRC cell survival
Akt↓,
p‑Akt↓,
p‑mTOR↓,
E-cadherin↑, enhancement of E-cadherin levels while simultaneously reducing N-cadherin and Vimentin
N-cadherin↓,
Vim↓,

8389- LT,    Luteolin-Manganese Nanozyme Induces Apoptosis and Ferroptosis for Enhanced Cancer Therapy
- in-vitro, Var, NA
ROS↑, In vitro experiments demonstrated that Lu-Mn exhibits a strong affinity for hydrogen peroxide (H2O2) and effectively catalyzes the generation of hydroxyl radicals (•OH) from H2O2 within the tumor microenvironment.
Apoptosis↑, not only induced apoptosis in tumor cells by upregulating the expression of cleaved caspase3 and caspase9 but also activated ferroptosis through downregulation of the NRF2-GPX4 signaling pathway
cl‑Casp3↑,
cl‑Casp9↑,
Ferroptosis↑,
NRF2↓,
GPx4↓,
IronCh↑, Collectively, these findings suggest that luteolin, through its chelation with metal ions, has considerable potential for application in cancer treatment.

8388- LT,    Untargeted metabolomics reveals the mechanisms of luteolin and exercise combination treatment against cognitive impairments in AD mice through modulating autophagy
- in-vivo, AD, NA
*autophagy↝, Lut + Exe could reverse the significant reduction of key autophagy proteins of AD model mice
*cognitive↑, Our group has previously found that AD-related cognitive impairment (ARCI) could be alleviated after luteolin and exercise combination treatment (Lut + Exe),

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↓,

8386- LT,    Luteolin induces apoptosis in Philadelphia chromosome-positive acute lymphoblastic leukemia cell by regulating the PI3K/AKT signaling pathway
- in-vitro, ALL, SUP-B15
tumCV↓, luteolin reduced the viability of SUP-B15 cells in a time- and concentration-dependent manner.
ROS↑, luteolin led to an increase in reactive oxygen species (ROS) accumulation, a decrease in mitochondrial membrane potential (MMP), and a reduction in ATP content in SUP-B15 cells.
MMP↓,
ATP↓,
p‑PI3K↓, luteolin significantly downregulated the protein expression of p-PI3K, p-AKT, p-STAT3 and BCL-2, while upregulating the protein expression of BAX, cleaved caspase-3, and cleaved caspase-9.
p‑Akt↓,
p‑STAT3↓,
Bcl-2↓,
BAX↑,
cl‑Casp3↑,
cl‑Casp9↑,
TumCP↓, Luteolin inhibits the proliferation of SUP-B15 cells in vitro
eff↓, We found that NAC partially reversed the apoptosis induction and mitochondrial membrane potential reduction induced by luteolin
ChemoSen↑, In drug-resistant esophageal cancer cells, luteolin functions to suppress the FAK/PI3K/AKT pathway, thereby sensitizing them to chemotherapeutic agents
FAK↓,
Synergy↑, combining luteolin with zinc oxide nanoparticles (ZnO NPs), zinc oxide nanoparticles-luteolin (ZnONPs-Lut), can induce ROS production, thereby inhibiting cell proliferation
BioAv↓, Additionally, the oral bioavailability of luteolin is low and its distribution within tissues is limited. high concentrations of luteolin (100 μM)can only be achieved in vitro experiments
BioAv↑, nanocarrier systems (such as liposomes, nanoparticles, and microemulsions) has significantly enhanced the bioavailability of luteolin


Showing Research Papers: 1 to 50 of 106
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 106

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   antiOx⇅, 1,   Catalase↓, 3,   Catalase↑, 2,   GPx↓, 1,   GPx4↓, 5,   GSH↓, 8,   GSH↑, 1,   GSR↓, 1,   GSS↑, 1,   GSTs↓, 2,   e-H2O2↓, 1,   i-H2O2∅, 1,   HO-1↓, 8,   HO-1↑, 1,   Iron↑, 3,   lipid-P↑, 2,   MDA↑, 3,   NQO1↓, 2,   NRF2↓, 10,   NRF2↑, 2,   NRF2⇅, 1,   PrxII↓, 1,   ROS↓, 5,   ROS↑, 23,   SOD↓, 8,   SOD↑, 1,   SOD2↓, 1,   Trx1↑, 2,   TrxR1↓, 1,   VitC↓, 1,   VitE↓, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

CDC2↓, 3,   compI↓, 1,   compIII↓, 1,   compV↓, 1,   ETC↓, 2,   mtDam↑, 3,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT∅, 1,   ATP↓, 2,   FASN↓, 2,   Glycolysis↓, 2,   GSK‐3β↓, 1,   GSK‐3β↑, 1,   p‑GSK‐3β↓, 1,   HK1↓, 1,   HK2↓, 1,   PKM2↓, 1,   p‑S6↓, 1,   SIRT1↓, 2,   SREBP2↓, 1,  

Cell Death(tgid=5) ⓘ

AIF↑, 1,   APAF1↑, 1,   Apoptosis↓, 2,   Apoptosis↑, 25,   ASC↓, 1,   BAD↑, 1,   BAX↑, 14,   Bax:Bcl2↑, 3,   Bcl-2↓, 14,   Bcl-xL↓, 3,   BID↑, 1,   BNIP3↑, 2,   BOK↑, 1,   Casp↑, 2,   Casp1↓, 1,   Casp12↑, 2,   cl‑Casp12↑, 1,   cl‑Casp12↝, 1,   Casp3↑, 11,   cl‑Casp3↑, 4,   Casp7↑, 1,   Casp8↑, 3,   cl‑Casp8↑, 1,   Casp9↑, 8,   cl‑Casp9↑, 4,   proCasp9↓, 1,   Cyt‑c↑, 7,   DR5↑, 6,   FADD↑, 1,   Fas↑, 4,   FasL↑, 1,   Ferroptosis↑, 6,   GranB/GZMB↑, 1,   GranB/GZMB↝, 1,   GSDMD↑, 1,   iNOS↓, 1,   Mcl-1?, 1,   Mcl-1↓, 2,   MDM2↓, 4,   p‑MDM2↓, 1,   NAIP↓, 1,   necrosis↑, 1,   p38↑, 1,   p‑p38↑, 2,   Perforin↑, 1,   Perforin↝, 1,   Pyro↑, 2,   survivin↓, 3,   TumCD↑, 1,   XIAP↓, 4,   YAP/TEAD↓, 3,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 12,   Akt↑, 1,   p‑Akt↓, 8,   AKT1↓, 3,   Akt2↓, 1,   AKT3↓, 1,   cMET↓, 1,   EGFR↓, 1,   EGFR↑, 1,   p‑EGFR↓, 1,   ERK↓, 2,   ERK↑, 1,   p‑ERK↓, 3,   HER2/EBBR2↓, 1,   HGF/c-Met↓, 2,   Hippo↝, 1,   IGF-1R↓, 2,   IKKα↓, 1,   JAK2↓, 2,   JNK↓, 1,   JNK↑, 4,   p‑JNK↑, 1,   LIMK1↓, 1,   p‑MAP2K1/MEK1↓, 1,   MAPK↓, 4,   MAPK↑, 2,   p‑MAPK↓, 1,   p‑MEK↓, 1,   mTOR↓, 4,   p‑mTOR↓, 2,   PI3K↓, 11,   p‑PI3K↓, 3,   PKCδ↓, 1,   PTEN↓, 1,   RAS↓, 1,   SGK1↓, 1,   p‑Src↓, 1,   STAT3↓, 8,   p‑STAT3↓, 5,   p‑STAT6↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

ATF2↓, 1,   ATF4↑, 2,   p‑ATF4↝, 1,   cMyc↓, 4,   p‑cMyc↑, 1,   DNMT1↓, 2,   DNMT3A↓, 1,   DNMTs↓, 2,   EZH2↓, 2,   FOXO1↓, 1,   FOXO3↑, 1,   H3↓, 1,   ac‑H3↓, 1,   H4↓, 1,   ac‑H4↓, 1,   HATs↓, 1,   HDAC↓, 4,   HES1↓, 2,   miR-107↑, 2,   miR-139-5p↑, 2,   miR-155↓, 2,   miR-21↓, 2,   miR-224↓, 2,   miR-29b↑, 1,   miR-30a-5p↑, 1,   miR-340↓, 2,   miR-34a↓, 1,   miR-34a↑, 2,   miR-34b-5p↑, 1,   miR-384↑, 2,   miR-422a↑, 2,   Myc↓, 1,   other↝, 1,   SD↑, 1,   SOX4↓, 1,   TET3↑, 1,   tumCV↓, 7,  

Protein Folding & ER Stress(tgid=8) ⓘ

cl‑ATF6↑, 1,   CHOP/DDIT3↑, 3,   p‑CHOP/DDIT3↝, 1,   eIF2α↑, 2,   p‑eIF2α↑, 2,   p‑eIF2α↝, 1,   ER Stress↑, 5,   GRP78/BiP↑, 1,   GRP94↑, 1,   HSP90↓, 3,   PERK↑, 2,   p‑PERK↝, 1,   UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1/ATG6↑, 5,   LC3B-II↑, 2,   LC3II↑, 3,   p62↓, 1,   TumAuto↑, 5,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   DNArepair↓, 1,   ERCC3↑, 1,   hTERT/TERT↓, 4,   NKX3.1↓, 1,   P53↑, 8,   PARP↑, 1,   cl‑PARP↑, 2,   PCNA↓, 2,   Telomerase↓, 3,   TOP1↓, 1,   TOP2↓, 1,   XRCC1↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 5,   CDK4↓, 3,   CDK6↓, 1,   p‑CHK1↑, 1,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 3,   cycD1/CCND1↓, 4,   cycE/CCNE↓, 1,   Ki-67↓, 4,   P21↓, 1,   P21↑, 5,   p27/CDKN1B↑, 2,   TumCCA↑, 15,  

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

ALDH1A1↓, 1,   CD34↓, 1,   cFos↑, 1,   CSCs↓, 2,   GDF15↓, 1,   IGF-1↓, 1,   IGF-2↓, 1,   Ki-67↓, 4,   MSCmark↓, 1,   NICD↓, 1,   NOTCH↓, 4,   NOTCH1↓, 3,   TAZ↓, 2,   TumCG↓, 5,   TumCP?, 1,   TumCP↓, 24,   WDR72↓, 1,   Wnt↓, 4,  

Migration(tgid=13) ⓘ

AEG1↓, 1,   AP-1↓, 1,   AXL↓, 1,   Ca+2↓, 1,   Ca+2↑, 3,   Cdc42↓, 1,   E-cadherin↓, 2,   E-cadherin↑, 8,   EM↑, 1,   EMT↓, 13,   FAK↓, 5,   ITGA6↓, 1,   ITGB1↓, 1,   MET↓, 1,   p‑MET↓, 1,   MMP1↓, 1,   MMP16↓, 3,   MMP2↓, 8,   MMP3↓, 3,   MMP9↓, 8,   MMPs↓, 2,   N-cadherin↓, 8,   PDGF↓, 1,   Rac1↓, 1,   Rho↓, 1,   Smad1↓, 1,   Snail↓, 4,   TET1↑, 2,   TGF-β↓, 1,   TGF-β1↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCA↓, 1,   TumCI↓, 8,   TumCMig↓, 11,   TumMeta↓, 5,   Twist↓, 2,   Tyro3↓, 1,   Vim↓, 7,   Vim↑, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 6,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 8,   ECM/TCF↓, 1,   HIF-1↓, 1,   Hif1a↓, 3,   VEGF↓, 6,   VEGFR1↓, 1,   VEGFR2/KDR/Flk1↓, 2,  

Barriers & Transport(tgid=15) ⓘ

CLDN1↓, 2,   CLDN2↓, 1,   MMP↓, 8,   OATPs↓, 1,   ZO-1↑, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD8+↑, 1,   COX2/PTGS2↓, 1,   CXCL16↓, 1,   CXCR4↓, 1,   HMGB1↓, 1,   ICAM-1↓, 1,   IFN-γ↓, 1,   IL1↓, 1,   IL18↓, 1,   IL1β↓, 1,   IL2↓, 1,   IL2↑, 1,   IL6↓, 4,   IL8↓, 1,   Imm↑, 1,   Imm↝, 1,   Inflam↓, 2,   pol-M1↑, 1,   NF-kB↓, 12,   p‑NF-kB↑, 1,   NLRP3↓, 1,   NLRP3↑, 1,   p50↓, 1,   p‑p65↓, 1,   PD-1↓, 1,   PD-L1↓, 4,   TCF↓, 1,   TNF-α↓, 3,  

Synaptic & Neurotransmission(tgid=18) ⓘ

PTN↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

AR↓, 4,   CYP19↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   BioAv↑, 4,   BioAv↝, 1,   ChemoSen↓, 1,   ChemoSen↑, 15,   CYP1A1↓, 2,   CYP1A2↓, 1,   Dose?, 1,   Dose↝, 5,   eff↓, 6,   eff↑, 6,   Half-Life↝, 1,   MDR1↓, 2,   P450↓, 1,   RadioS↑, 4,   selectivity↑, 4,   Synergy↑, 2,   TET2↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT∅, 1,   AR↓, 4,   AST∅, 1,   CEA↓, 1,   EGFR↓, 1,   EGFR↑, 1,   p‑EGFR↓, 1,   EZH2↓, 2,   HER2/EBBR2↓, 1,   hTERT/TERT↓, 4,   IL6↓, 4,   Myc↓, 1,   NSE↓, 1,   PD-L1↓, 4,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 2,   cachexia↓, 1,   cardioP↑, 1,   chemoP↑, 4,   chemoPv↑, 1,   hepatoP↑, 1,   Pain↓, 1,   TumVol↓, 1,   TumVol∅, 1,   TumW∅, 1,   Weight∅, 1,  

Infection & Microbiome(tgid=24) ⓘ

GutMicro↑, 1,  
Total Targets: 371

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 15,   ARE↑, 1,   Catalase↓, 1,   Catalase↑, 7,   GPx↑, 3,   GPx4∅, 1,   GSH↑, 8,   GSR↑, 2,   GSTs↓, 2,   GSTs↑, 2,   HO-1↑, 6,   HO-1∅, 1,   Iron↝, 1,   lipid-P↓, 9,   MDA↓, 5,   MDA↑, 1,   NQO1↑, 2,   NRF2↓, 2,   NRF2↑, 12,   NRF2∅, 1,   PrxII↑, 1,   ROS↓, 28,   SOD↓, 1,   SOD↑, 12,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

DRP1/DNM1L↓, 1,   FIS1↓, 1,   MFN2↑, 1,   mtDam↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACSL4∅, 1,   ALAT↓, 1,   AMPK↑, 2,   ATP↑, 2,   cytoP450↓, 1,   GSK‐3β↓, 3,   LDHA↑, 1,   PLA2↓, 1,   SIRT1↑, 2,   SREBP1/SREBF1↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 6,   BAX↓, 5,   Bax:Bcl2↓, 1,   Bcl-2↓, 2,   Bcl-2↑, 2,   Casp1↓, 2,   proCasp1↓, 1,   Casp3↓, 8,   cl‑Casp3↓, 1,   Casp9↓, 3,   Casp9↑, 1,   cl‑Casp9↓, 1,   Cyt‑c↓, 2,   Ferroptosis↓, 1,   iNOS↓, 3,   p‑p38↓, 1,   Pyro↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 1,   Akt↑, 3,   p‑Akt↓, 1,   CREB↑, 1,   ERK↓, 1,   p‑ERK↓, 1,   JNK↓, 1,   p‑JNK↓, 2,   MAPK↓, 1,   p‑MEK↓, 1,   p‑MKK4↑, 1,   mTOR↑, 2,   p‑mTOR↓, 1,   PI3K↓, 1,   PI3K↑, 3,   Raf↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

AntiThr↑, 1,   ATF4↓, 1,   HDAC2↓, 1,   other↓, 2,   other↝, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 1,   ER Stress↓, 4,   GRP78/BiP↓, 2,   GRP78/BiP↑, 1,   IRE1↓, 1,   UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

autophagy↝, 1,   Beclin-1/ATG6↓, 3,  

DNA Damage & Repair(tgid=10) ⓘ

p‑γH2AX↓, 1,  

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

Diff↝, 1,   neuroG↑, 3,  

Migration(tgid=13) ⓘ

AntiAg↑, 3,   AP-1↓, 1,   E-cadherin↑, 1,   MMP1↓, 1,   MMP9↓, 1,   PDGF↓, 1,   p‑T-cadherin↓, 1,   TregCell↑, 1,   TXNIP↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 3,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 5,   BBB∅, 2,   IBI↑, 1,   MMP↑, 5,   OATPs↓, 2,   TJ↑, 1,   ZO-1↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

AIF1/Iba-1↓, 1,   COX2/PTGS2↓, 6,   COX2/PTGS2∅, 1,   IFN-γ↓, 1,   IL10↓, 1,   IL10↑, 1,   IL18↓, 1,   IL1β↓, 6,   IL2↓, 1,   IL33↓, 1,   IL4↓, 1,   IL5↓, 1,   IL6↓, 5,   IL8↓, 1,   Inflam↓, 14,   pol-M2 MC↑, 1,   MCP1/CCL2↓, 1,   NeuroI↓, 3,   NF-kB↓, 5,   p‑NF-kB↓, 1,   NLRP3↓, 3,   PGE2↓, 2,   RANTES↓, 1,   TLR4↓, 1,   TNF-α↓, 7,  

Cellular Microenvironment(tgid=17) ⓘ

GFAP↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

5HT↓, 1,   AChE↓, 6,   BDNF↑, 6,   ChAT↑, 1,   PSD95↑, 3,   SNAP25↑, 2,   TPH1↓, 1,   TrkB↑, 2,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 7,   Aβ42↓, 4,   BACE/β-secretase↓, 4,   IDE↑, 1,   tau↓, 2,   p‑tau↓, 3,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

PPARα↑, 1,   PPARγ↑, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 7,   BioAv↑, 3,   BioAv↝, 1,   eff↑, 4,   GSTA1↑, 2,   Half-Life↝, 2,   Synergy↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   BloodF↑, 1,   IL6↓, 5,   IRes↓, 1,  

Functional Outcomes(tgid=23) ⓘ

antiAll↑, 3,   AntiCan↑, 1,   AntiDiabetic↑, 1,   AntiTum↑, 1,   cardioP↑, 3,   cognitive↑, 7,   hepatoP↑, 3,   Learn↑, 2,   memory↑, 6,   Mood↑, 2,   motorD↑, 2,   Mucositis↓, 2,   neuroP↑, 12,   OS↑, 1,   RenoP↑, 2,   Stroke↓, 1,   toxicity↓, 4,   toxicity↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

AntiBio↑, 1,   GutMicro↑, 2,   Sepsis↓, 1,  
Total Targets: 181

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#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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