Luteolin / ROS 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↓">ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, LDHA↓, HK2↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, TrxR**, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

-"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.


ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)
ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy 
ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination




Item ROS↑ NRF2 Condition Mechanism Class Remarks 



ROS">Piperlongumine
+++ ↓ [D][T] ROS-dominant






ROS">Shikonin
+++↓/±[D][T]ROS-dominant






ROS">Vitamin K3 (menadione)
+++↓[D]ROS-dominant






ROS">Copper (ionic / nano)
+++↓[Fe][F]ROS-dominant






ROS">Sodium Selenite
+++↓[D]ROS-dominant






ROS">Juglone
+++↓[D]ROS-dominant






ROS">Auranofin
+++↓[D]ROS-dominant






ROS">Photodynamic Therapy (PDT)
+++0[L][O₂]ROS-dominant






ROS">Radiotherapy / Radiation
+++0[O₂]ROS-dominant






ROS">Doxorubicin
+++↓[D]ROS-dominant






ROS">Cisplatin
++↓[D][T]ROS-dominant






ROS">Salinomycin
++↓[D][T]ROS-dominant






ROS">Artemisinin / DHA
++↓[Fe][T]ROS-dominant






ROS">Sulfasalazine
++↓[C][T]ROS-dominant






ROS">FMD / fasting
++↓[M][C][O₂]ROS-dominant






ROS">Vitamin C (pharmacologic)
++↓[Fe][D]ROS-dominant






ROS">Silver nanoparticles
++±[F][D]ROS-dominant






ROS">Gambogic acid
++↓[D][T]ROS-dominant






ROS">Parthenolide
++↓[D][T]ROS-dominant






ROS">Plumbagin
++↓[D]ROS-dominant






ROS">Allicin
++↓[D]ROS-dominant






ROS">Ashwagandha (Withaferin A)
++↓[D][T]ROS-dominant






ROS">Berberine
++↓[D][M]ROS-dominant






ROS">PEITC
++↓[D][C]ROS-dominant






ROS">Methionine restriction
+↓[M][C][T]ROS-secondary






ROS">DCA
+±[M][T]ROS-secondary






ROS">Capsaicin
+±[D][T]ROS-secondary






ROS">Galloflavin
+0[D]ROS-secondary






ROS">Piperine
+±[D][F]ROS-secondary






ROS">Propyl gallate
+↓[D]ROS-secondary






ROS">Scoulerine
+?[D][T]ROS-secondary






ROS">Thymoquinone
±±[D][T]Dual redox






ROS">Emodin
±±[D][T]Dual redox






ROS">Alpha-lipoic acid (ALA)
±↑[D][M]NRF2-dominant






ROS">Curcumin
±↑/↓[D][F]NRF2-dominant






ROS">EGCG
±↑/↓[D][O₂]NRF2-dominant






ROS">Quercetin
±↑/↓[D][Fe]NRF2-dominant






ROS">Resveratrol
±↑[D][M]NRF2-dominant






ROS">Sulforaphane
±↑↑[D]NRF2-dominant






ROS">Lycopene
0↑—Antioxidant






ROS">Rosmarinic acid
0↑—Antioxidant






ROS">Citrate
00—Neutral


Scientific Papers found: Click to Expand⟱
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

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

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↑,

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↝,

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↑,

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,

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

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.

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↓,

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↓,

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.

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

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

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

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

2905- LT,    Luteolin blocks the ROS/PI3K/AKT pathway to inhibit mesothelial-mesenchymal transition and reduce abdominal adhesions
- in-vivo, Nor, HMrSV5
*ROS↓, It attenuated H2O2-induced ROS production and reversed mesothelial-mesenchymal transition (MMT) in HMrSV5 cells.
*p‑Akt↓, Phosphorylated Akt levels were significantly reduced in LUT-treated HMrSV5 cells
*Vim↓, LUT also significantly reduced the expression of vimentin and collagen I in adherent tissues and upregulated E-cadherin expression
*E-cadherin↑,
*PI3K↓, LUT blocks the ROS/PI3K/AKT pathway, thereby inhibiting MMT and reducing PAA.

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

2903- LT,    Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG - in-vivo, NA, NA
ER Stress↑, Luteolin induced a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in glioblastoma cells by increasing intracellular reactive oxygen species (ROS) levels.
ROS↑,
PERK↑, Luteolin induced expression of ER stress-associated proteins, including phosphorylation of PERK, eIF2α, ATF4, CHOP and cleaved-caspase 12.
eIF2α↑,
ATF4↑,
CHOP/DDIT3↑,
Casp12↑,
eff↓, Inhibition of ROS production by anti-oxidant N-acetylcysteine could reverse luteolin-induced ER stress and mitochondrial pathways activation as well as apoptosis.
UPR↑, Researches indicate that abnormalities in ER function can cause ER stress, resulting in unfolded protein response (UPR),
MMP↓, integrity of mitochondrial membranes potential decreased in U87MG cells after treatment of 40 uM luteolin
Cyt‑c↑, release of cytochrome C to cytoplasm was elevated in U251MG cells
Bcl-2↓, significantly decreased the expression of anti-apoptotic protein Bcl-2 and increased the expression of pro-apoptotic protein Bax in U251MG and U87MG glioblastoms cells.
BAX↑,
TumCG↓, Luteolin inhibited tumor growth in a xenograft mouse model
Weight∅, luteolin did not affect body weight, alanine aminotransferase (ALT) or aspartate transaminase (AST)
ALAT∅,
AST∅,

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

1100- LT,    Luteolin, a flavonoid, as an anticancer agent: A review
- Review, Var, NA
TumCP↓,
TumCCA↑,
Apoptosis↑,
EMT↓, reverse epithelial-mesenchymal transition (EMT)
E-cadherin↑,
N-cadherin↓,
Snail↓,
Vim↓,
ROS↑, Luteolin increases levels of intracellular reactive oxygen species (ROS) by activation
ER Stress↑,
mtDam↑, mitochondrial dysfunction
p‑eIF2α↝,
p‑PERK↝,
p‑CHOP/DDIT3↝,
p‑ATF4↝,
cl‑Casp12↝,

1084- LT,  CHr,    Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells
- in-vitro, Nor, RAW264.7
*COX2/PTGS2↓, 25, 50, or 100 micromol/L concentrations of luteolin inhibited (lipopolysaccharide (LPS)-induced) Cox-2 protein expression
*COX2/PTGS2∅, Chrysin pretreatment did not reduce (LPS-induced) Cox-2 protein expression at any level tested.
*PGE2↓, both luteolin and chrysin completely suppressed (LPS-induced) PGE2 formation
*ROS↓, only Luteolin suppressed superoxide formation (induced by xanthine)

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

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

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

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

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

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↑,

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

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↓,

2913- LT,    Luteolin induces apoptosis by impairing mitochondrial function and targeting the intrinsic apoptosis pathway in gastric cancer cells
- in-vitro, GC, HGC27 - in-vitro, BC, MCF7 - in-vitro, GC, MKN45
TumCP↓, Luteolin inhibited the proliferation of gastric cancer HGC-27, MFC and MKN-45 cells
MMP↓, impaired mitochondrial integrity and function by destroying the mitochondrial membrane potential,
Apoptosis↑, eventually leading to apoptosis of gastric cancer HGC-27, MFC and MKN-45 cells
ROS↑, luteolin-induced ROS accumulation in HGC-27, MFC and MKN-45 cells. HGC-27 and MFC cells were treated with luteolin (10, 40, and 70 µM) for 24 h, and MKN-45 cells were treated for 48 h
SOD↓, suggested that luteolin could induce SOD activity reduction, especially in the high dose of luteolin groups in HGC-27 and MFC cells
ATP↓, ATP content decreased, especially in the high-dose groups
Bax:Bcl2↑, luteolin significantly decreased the ratio between Bcl-2 and Bax in HGC-27, MFC, and MKN-45 cells
TumCCA↑, In addition, it is reported that luteolin could induce cell cycle arrest and apoptosis through extrinsic and intrinsic signaling pathways in MCF-7 breast cancer cell

2912- LT,    Luteolin: a flavonoid with a multifaceted anticancer potential
- Review, Var, NA
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 46 of 46

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 46

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   antiOx⇅, 1,   Catalase↓, 2,   Catalase↑, 2,   GPx↓, 1,   GPx4↓, 4,   GSH↓, 5,   GSH↑, 1,   GSR↓, 1,   GSS↑, 1,   GSTs↓, 2,   HO-1↓, 4,   HO-1↑, 1,   Iron↑, 2,   lipid-P↑, 2,   MDA↑, 2,   NQO1↓, 1,   NRF2↓, 5,   NRF2↑, 2,   ROS↓, 5,   ROS↑, 23,   SOD↓, 6,   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↓, 1,   GSK‐3β↓, 1,   p‑GSK‐3β↓, 1,   HK1↓, 1,   p‑S6↓, 1,   SIRT1↓, 1,  

Cell Death(tgid=5) ⓘ

AIF↑, 1,   APAF1↑, 1,   Apoptosis↑, 11,   ASC↓, 1,   BAD↑, 1,   BAX↑, 12,   Bax:Bcl2↑, 3,   Bcl-2↓, 12,   Bcl-xL↓, 2,   BID↑, 1,   BNIP3↑, 1,   BOK↑, 1,   Casp↑, 2,   Casp1↓, 1,   Casp12↑, 1,   cl‑Casp12↑, 1,   cl‑Casp12↝, 1,   Casp3↑, 9,   cl‑Casp3↑, 4,   Casp8↑, 3,   cl‑Casp8↑, 1,   Casp9↑, 7,   cl‑Casp9↑, 4,   proCasp9↓, 1,   Cyt‑c↑, 6,   DR5↑, 6,   FADD↑, 1,   Fas↑, 4,   FasL↑, 1,   Ferroptosis↑, 4,   GranB/GZMB↝, 1,   iNOS↓, 1,   Mcl-1?, 1,   Mcl-1↓, 1,   MDM2↓, 3,   p‑MDM2↓, 1,   NAIP↓, 1,   p‑p38↑, 2,   Perforin↝, 1,   survivin↓, 2,   XIAP↓, 4,   YAP/TEAD↓, 2,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 7,   Akt↑, 1,   p‑Akt↓, 6,   AKT1↓, 2,   Akt2↓, 1,   EGFR↓, 1,   EGFR↑, 1,   p‑EGFR↓, 1,   ERK↓, 2,   p‑ERK↓, 2,   HGF/c-Met↓, 1,   Hippo↝, 1,   IGF-1R↓, 1,   IKKα↓, 1,   JAK2↓, 1,   JNK↑, 3,   p‑JNK↑, 1,   LIMK1↓, 1,   p‑MAP2K1/MEK1↓, 1,   MAPK↓, 3,   MAPK↑, 2,   p‑MAPK↓, 1,   mTOR↓, 3,   p‑mTOR↓, 2,   PI3K↓, 8,   p‑PI3K↓, 3,   PKCδ↓, 1,   PTEN↓, 1,   RAS↓, 1,   p‑Src↓, 1,   STAT3↓, 4,   p‑STAT3↓, 2,   p‑STAT6↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

ATF2↓, 1,   ATF4↑, 2,   p‑ATF4↝, 1,   cMyc↓, 3,   p‑cMyc↑, 1,   DNMT1↓, 1,   DNMT3A↓, 1,   DNMTs↓, 1,   FOXO1↓, 1,   FOXO3↑, 1,   H3↓, 1,   H4↓, 1,   HDAC↓, 2,   HES1↓, 2,   miR-107↑, 1,   miR-139-5p↑, 1,   miR-155↓, 1,   miR-21↓, 1,   miR-224↓, 1,   miR-340↓, 1,   miR-34a↓, 1,   miR-34a↑, 1,   miR-34b-5p↑, 1,   miR-384↑, 2,   miR-422a↑, 1,   TET3↑, 1,   tumCV↓, 5,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 2,   p‑CHOP/DDIT3↝, 1,   eIF2α↑, 2,   p‑eIF2α↑, 1,   p‑eIF2α↝, 1,   ER Stress↑, 4,   PERK↑, 2,   p‑PERK↝, 1,   UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

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

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   DNArepair↓, 1,   ERCC3↑, 1,   hTERT/TERT↓, 3,   P53↑, 5,   PARP↑, 1,   cl‑PARP↑, 2,   PCNA↓, 1,   Telomerase↓, 3,   TOP1↓, 1,   TOP2↓, 1,   XRCC1↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 5,   CDK4↓, 2,   p‑CHK1↑, 1,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 3,   cycD1/CCND1↓, 2,   Ki-67↓, 2,   P21↓, 1,   P21↑, 5,   p27/CDKN1B↑, 2,   TumCCA↑, 10,  

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

CD34↓, 1,   cFos↑, 1,   IGF-1↓, 1,   IGF-2↓, 1,   Ki-67↓, 2,   NICD↓, 1,   NOTCH↓, 3,   NOTCH1↓, 3,   TAZ↓, 1,   TumCG↓, 2,   TumCP?, 1,   TumCP↓, 12,   Wnt↓, 2,  

Migration(tgid=13) ⓘ

AEG1↓, 1,   AXL↓, 1,   Ca+2↑, 3,   Cdc42↓, 1,   E-cadherin↓, 2,   E-cadherin↑, 7,   EMT↓, 10,   FAK↓, 4,   ITGB1↓, 1,   MET↓, 1,   p‑MET↓, 1,   MMP1↓, 1,   MMP16↓, 2,   MMP2↓, 6,   MMP3↓, 2,   MMP9↓, 6,   MMPs↓, 1,   N-cadherin↓, 8,   PDGF↓, 1,   Rac1↓, 1,   Rho↓, 1,   Smad1↓, 1,   Snail↓, 4,   TET1↑, 2,   TGF-β1↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumMeta↓, 2,   Twist↓, 2,   Tyro3↓, 1,   Vim↓, 7,   Vim↑, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature(tgid=14) ⓘ

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

Barriers & Transport(tgid=15) ⓘ

CLDN1↓, 2,   MMP↓, 7,   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,   IL2↑, 1,   IL6↓, 2,   Imm↑, 1,   Imm↝, 1,   Inflam↓, 1,   pol-M1↑, 1,   NF-kB↓, 11,   p‑NF-kB↑, 1,   NLRP3↓, 1,   p‑p65↓, 1,   PD-1↓, 1,   PD-L1↓, 2,   TCF↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission(tgid=18) ⓘ

PTN↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

AR↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 1,   ChemoSen↓, 1,   ChemoSen↑, 6,   CYP1A1↓, 2,   CYP1A2↓, 1,   Dose↝, 1,   eff↓, 3,   eff↑, 2,   Half-Life↝, 1,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 4,   selectivity↑, 2,   Synergy↑, 2,   TET2↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT∅, 1,   AR↓, 2,   AST∅, 1,   CEA↓, 1,   EGFR↓, 1,   EGFR↑, 1,   p‑EGFR↓, 1,   hTERT/TERT↓, 3,   IL6↓, 2,   NSE↓, 1,   PD-L1↓, 2,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   cachexia↓, 1,   cardioP↑, 1,   chemoP↑, 2,   hepatoP↑, 1,   Pain↓, 1,   Weight∅, 1,  

Infection & Microbiome(tgid=24) ⓘ

GutMicro↑, 1,  
Total Targets: 300

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 12,   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,   NQO1↑, 2,   NRF2↓, 1,   NRF2↑, 11,   NRF2∅, 1,   ROS↓, 28,   SOD↓, 1,   SOD↑, 11,  

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↑, 1,   GSK‐3β↓, 2,   LDHA↑, 1,   PLA2↓, 1,   SIRT1↑, 2,   SREBP1/SREBF1↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 3,   BAX↓, 5,   Bax:Bcl2↓, 1,   Bcl-2↓, 2,   Bcl-2↑, 2,   Casp1↓, 2,   proCasp1↓, 1,   Casp3↓, 7,   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↑, 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,   PI3K↓, 1,   PI3K↑, 3,   Raf↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

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

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 1,   ER Stress↓, 3,   GRP78/BiP↓, 2,   GRP78/BiP↑, 1,   IRE1↓, 1,   UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1/ATG6↓, 3,  

DNA Damage & Repair(tgid=10) ⓘ

p‑γH2AX↓, 1,  

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

Diff↝, 1,   neuroG↑, 2,  

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↑, 4,   BBB∅, 2,   IBI↑, 1,   MMP↑, 4,   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↓, 12,   MCP1/CCL2↓, 1,   NeuroI↓, 1,   NF-kB↓, 4,   NLRP3↓, 3,   PGE2↓, 2,   RANTES↓, 1,   TLR4↓, 1,   TNF-α↓, 7,  

Cellular Microenvironment(tgid=17) ⓘ

GFAP↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

5HT↓, 1,   AChE↓, 4,   BDNF↑, 3,   ChAT↑, 1,   PSD95↑, 2,   SNAP25↑, 2,   TPH1↓, 1,   TrkB↑, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 6,   Aβ42↓, 4,   BACE/β-secretase↓, 4,   IDE↑, 1,   tau↓, 1,   p‑tau↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

PPARα↑, 1,   PPARγ↑, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 6,   BioAv↑, 3,   BioAv↝, 1,   eff↑, 4,   GSTA1↑, 1,   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,   cardioP↑, 2,   cognitive↑, 5,   hepatoP↑, 3,   Learn↑, 2,   memory↑, 6,   motorD↑, 2,   Mucositis↓, 2,   neuroP↑, 10,   OS↑, 1,   RenoP↑, 2,   Stroke↓, 1,   toxicity↓, 3,  

Infection & Microbiome(tgid=24) ⓘ

AntiBio↑, 1,   GutMicro↑, 2,   Sepsis↓, 1,  
Total Targets: 168

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
46 Luteolin
2 Radiotherapy/Radiation
1 Baicalein
1 Mung Bean Sprouts
1 Myricetin
1 Kaempferol
1 Quercetin
1 Apigenin (mainly Parsley)
1 Chrysin
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#:275  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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