Database Query Results : Thymoquinone, , LDH

TQ, Thymoquinone: Click to Expand ⟱
Features: Anti-oxidant, anti-tumor
Thymoquinone is a bioactive compound found in the seeds of Nigella sativa, commonly known as black seed or black cumin.
Pathways:
-Cell cycle arrest, apoptosis induction, ROS generation in cancer cells
-inhibit the activation of NF-κB, Suppress the PI3K/Akt signaling cascade
-Inhibit angiogenic factors such as VEGF, MMPs
-Inhibit HDACs, UHRF1, and DNMTs

-Note half-life 3-6hrs.
BioAv low oral bioavailability due to its lipophilic nature. Note refridgeration of Black seed oil improves the stability of TQ.
DIY: ~1 part lecithin : 2–3 parts black seed oil : 4–5 parts warm water. (chat ai)
Pathways:
- usually induce ROS production in Cancer cells, and lowers ROS in normal cells
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- May Low AntiOxidant defense in Cancer Cells: NRF2↓(usually contrary), GSH↓ HO1↓(contrary), GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, VEGF↓, FAK↓, NF-κB↓, CXCR4↓, TGF-β↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH, LDH">LDHA↓, HK2↓, PDKs↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Target Axis Direction Label Primary Effect Notes / Cancer Relevance Ref
1 Reactive oxygen species (ROS) ↑ ROS Driver Upstream cytotoxic trigger Primary studies show TQ rapidly increases ROS; antioxidant/ROS modulation attenuates downstream effects, supporting ROS as an initiating mechanism in multiple cancer contexts (ref)
2 Glutathione (GSH) redox buffering ↓ GSH Driver Redox-collapse amplification Same prostate cancer study reports early GSH depletion alongside ROS rise; together these form a redox “one-two punch” that helps explain selective stress in tumor cells (ref)
3 Mitochondrial integrity (ΔΨm) ↓ ΔΨm Driver Mitochondrial dysfunction (MOMP axis) Primary leukemia/cancer study reports disruption of mitochondrial membrane potential after TQ exposure (mitochondrial events central to TQ-mediated death) (ref)
4 Intrinsic apoptosis (caspase-9 → caspase-3; PARP) ↑ caspases / ↑ apoptosis Driver Execution-phase cell death Same primary paper reports activation of caspases (8/9/3) with mitochondrial involvement—core evidence for apoptosis as the major outcome pathway (ref)
5 NF-κB signaling ↓ NF-κB activity Secondary Reduced pro-survival / inflammatory transcription Colon cancer work: TQ induces cell death and chemosensitizes cells by inhibiting NF-κB signaling (explicit pathway-direction support) (ref)
6 STAT3 signaling ↓ p-STAT3 / ↓ STAT3 activation Secondary Reduced survival/proliferation signaling Gastric cancer study explicitly reports TQ suppresses constitutive STAT3 activation and related signaling readouts (ref)
7 NRF2 antioxidant-response axis (NRF2/HO-1 program) ↑ NRF2 pathway (often as stress-response) Adaptive Cellular antioxidant counter-response In TNBC context, a primary study reports TQ upregulates NRF2 (and evaluates downstream immune/checkpoint consequences), consistent with NRF2 acting as an adaptive response to redox stress (ref)
8 HIF-1α hypoxia signaling ↓ HIF-1α protein / ↓ HIF-1α program Adaptive Loss of hypoxia survival signaling Renal cancer hypoxia paper identifies TQ as suppressing HIF-1α and links this to selective killing under hypoxia (ref)
9 Glycolysis / Warburg output (hypoxia-linked) ↓ glycolysis (↓ HIF-1α–mediated glycolytic genes; ↓ glycolytic metabolism) Phenotypic Metabolic suppression In hypoxic renal cancer, TQ suppresses HIF-1α–mediated glycolysis; in CRC, TQ inhibits glycolytic metabolism alongside tumor growth limitation (ref)  |  (ref)


LDH, Lactate Dehydrogenase: Click to Expand ⟱
Source:
Type:
LDH is a general term that refers to the enzyme that catalyzes the interconversion of lactate and pyruvate. LDH is a tetrameric enzyme, meaning it is composed of four subunits.
LDH refers to the enzyme as a whole, while LDHA specifically refers to the M subunit. Elevated LDHA levels are often associated with poor prognosis and aggressive tumor behavior, similar to elevated LDH levels.
leakage of LDH is a well-known indicator of cell membrane integrity and cell viability [35]. LDH leakage results from the breakdown of the plasma membrane and alterations in membrane permeability, and is widely used as a cytotoxicity endpoint.

However, it's worth noting that some studies have shown that LDHA is a more specific and sensitive biomarker for cancer than total LDH, as it is more closely associated with the Warburg effect and cancer metabolism.

Dysregulated LDH activity contributes significantly to cancer development, promoting the Warburg effect (Chen et al., 2007), which involves increased glucose uptake and lactate production, even in the presence of oxygen, to meet the energy demands of rapidly proliferating cancer cells (Warburg and Minami, 1923; Dai et al., 2016b). LDHA overexpression favors pyruvate to lactate conversion, leading to tumor microenvironment acidification and aiding cancer progression and metastasis.

Inhibitors:
Flavonoids, a group of polyphenols abundant in fruit, vegetables, and medicinal plants, function as LDH inhibitors.
LDH is used as a clinical biomarker for Synthetic liver function, nutrition


Tier A — Direct LDH Enzyme Inhibitors (Validated Catalytic Inhibition)

Rank Compound Type LDH Target Potency Level Primary Effect Notes
1 NCI-006 Research drug LDHA / LDHB High (in vivo active) Potent glycolysis suppression Modern benchmark LDH inhibitor used in metabolic oncology models.
2 (R)-GNE-140 Research drug LDHA (±LDHB) High (nM range reported) Lactate production ↓ Widely used experimental LDH inhibitor.
3 FX11 Research drug LDHA High (μM range) Metabolic crisis in LDHA-dependent tumors Classic LDHA inhibitor; often increases ROS secondary to metabolic stress.
4 Oxamate Tool compound LDH (pyruvate-competitive) Moderate (mM cellular use) Reduces lactate flux Classical LDH inhibitor; requires high concentrations in cells.
5 Gossypol Natural product derivative LDHA Moderate–High Glycolysis inhibition Also has other targets; safety considerations apply.
6 Galloflavin Natural compound LDH isoforms Moderate Lactate production ↓ One of the better-supported “natural-like” LDH inhibitors.

Tier B — Indirect LDH-Axis Modulators (Glycolysis / Lactate Reduction Without Confirmed Direct Catalytic Inhibition)

Rank Compound Mechanism Type LDH Claim Type Primary Axis Notes / Caution
1 Lonidamine MCT/MPC modulation Lactate axis inhibition Metabolic transport blockade Better classified as lactate/pyruvate transport modulator.
2 Stiripentol Repurposed drug LDH pathway modulation Metabolic axis modulation Emerging oncology interest; primarily neurological drug.
3 Quercetin Flavonoid Reported LDH inhibition (mixed evidence) NF-κB / PI3K modulation Often LDH-release confusion; direct enzymatic proof limited.
4 Ursolic acid Triterpenoid Reported LDH interaction Warburg modulation More credible as metabolic signaling modulator.
5 Fisetin Flavonoid Docking / indirect reports Apoptosis / survival signaling Enzyme inhibition not well validated.
6 Resveratrol Polyphenol Indirect glycolysis suppression AMPK / HIF-1α modulation Reduces lactate via upstream signaling.
7 Curcumin Polyphenol Indirect LDH expression modulation Inflammation + metabolic signaling Bioavailability limits translational strength.
8 Berberine Alkaloid Indirect metabolic modulation AMPK activation Closer to metformin-like metabolic pressure.
9 Honokiol Lignan Indirect glycolysis effects Survival pathway suppression Not validated as catalytic LDH inhibitor.
10 Silibinin Flavonolignan Mixed / indirect reports Inflammation + metabolic axis Often misclassified as LDH inhibitor.
11 Kaempferol Flavonoid Often LDH-release marker confusion Glucose transport / signaling Do not list as direct LDH inhibitor without enzyme data.
12 Oleanolic acid / Limonin / Allicin / Taurine Natural compounds Weak / indirect evidence General metabolic modulation Should not be categorized as true LDH inhibitors.

Tier A = Direct catalytic LDH inhibition (enzyme-level validation).
Tier B = Indirect lactate reduction or glycolytic modulation without strong catalytic inhibition evidence.
Important: LDH release assays (cell damage marker) are not proof of LDH enzymatic inhibition.



Scientific Papers found: Click to Expand⟱
3398- TQ,  5-FU,    Impact of thymoquinone on the Nrf2/HO-1 and MAPK/NF-κB axis in mitigating 5-fluorouracil-induced acute kidney injury in vivo
- in-vivo, Nor, NA
*RenoP↑, Pre-, post-, and cotreatment with TQ alleviated kidney injury
*TAC↑, by replenishing antioxidant reserves, reducing serum toxicity, decreasing ROS generation and lipid peroxidation, downregulating p38 MAPK/NF-κB axis/pathway proteins, and upregulating Nrf2 and HO-1,
*ROS↓, high-dose TQ alleviated ROS and H2O2 levels in groups III and IV
*lipid-P↓,
*p38↓,
*MAPK↓,
*NF-kB↓,
*NRF2↑,
*HO-1↑,
*MDA↓, TQ diminishes MDA levels
*GPx↑, GPx, GR, and CAT : restoration of GSH reserves and the abovementioned antioxidant enzymes
*GSR↑,
*Catalase↑,
*BUN↓, noticeable inhibition was observed in BUN, Cr, LDH, and KIM-1 at both doses
*LDH↓,
*IL1β↓, downregulation of IL-1β, diminishing inflammation

3559- TQ,    Molecular signaling pathway targeted therapeutic potential of thymoquinone in Alzheimer’s disease
- Review, AD, NA - Review, Var, NA
*antiOx↑, promising potential in the prevention and treatment of AD due to its significant antioxidative, anti-inflammatory,
*Inflam↓, anti-inflammatory activity of TQ is mediated through the Toll-like receptors (TLRs)
*AChE↓, In addition, it shows anticholinesterase activity and prevents α-synuclein induced synaptic damage.
AntiCan↑, NS plant, has been proven to have a wide range of pharmacological interventions, including antidiabetic, anticancer, cardioprotective, retinoprotective, renoprotective, neuroprotective, hepatoprotective and antihypertensive effects
*cardioP↑,
*RenoP↑,
*neuroP↑,
*hepatoP↑,
TumCG↓, potential ability to inhibit tumor growth by stimulating apoptosis as well as by suppression of the P13K/Akt pathways, cell cycle arrest and by inhibition of angiogenesis
Apoptosis↑,
PI3K↓,
Akt↑,
TumCCA↑,
angioG↓,
*NF-kB↓, TQ inhibits nuclear translocation of NF-kB which subsequently blocks the production of NF-kB mediated neuroinflammatory cytokines
*TLR2↓, TQ administration at different doses (10, 20, 40 mg/kg) significantly down-regulated the mRNA expression of TLR-2, TLR-4, MyD88, TRIF and their downstream effectors Interferon regulatory factor 3 (IRF-3)
*TLR4↓,
*MyD88↓,
*TRIF↓,
*IRF3↓,
*IL1β↓, TQ also inhibits LPS induced pro-inflammatory cytokine release like IL-1B, IL-6 and IL-12 p40/70 via its interaction with NF-kB
*IL6↓,
*IL12↓,
*NRF2↑, Nuclear erythroid-2 related factor/antioxidant response element (Nrf 2/ARE) being an upstream signaling pathway of NF-kB signaling pathway, its activation by TQ
*COX2↓, TQ also inhibits the expression of all genes regulated by NF-kB, i.e., COX-2, VEGF, MMP-9, c-Myc, and cyclin D1 which distinctively lowers NF-kB activation making it a potentially effective inhibitor of inflammation, proliferation and invasion
*VEGF↓,
*MMP9↓,
*cMyc↓,
*cycD1/CCND1↓,
*TumCP↓,
*TumCI↓,
*MDA↓, it prevents the rise of malondialdehyde (MDA), transforming growth factor beta (TGF-β), c-reactive protein, IL1-β, caspase-3 and concomitantly upregulates glutathione (GSH), cytochrome c oxidase, and IL-10 levels [92].
*TGF-β↓,
*CRP↓,
*Casp3↓,
*GSH↑,
*IL10↑,
*iNOS↑, decline of inducible nitric oxide synthase (iNOS) protein expression
*lipid-P↓, TQ prominently mitigated hippocampal lipid peroxidation and improved SOD activity
*SOD↑,
*H2O2↓, TQ is a strong hydrogen peroxide, hydroxyl scavenger and lipid peroxidation inhibitor
*ROS↓, TQ (0.1 and 1 μM) ensured the inhibition of free radical generation, lowering of the release of lactate dehydrogenase (LDH)
*LDH↓,
*Catalase↑, upsurge the levels of GSH, SOD, catalase (CAT) and glutathione peroxidase (GPX)
*GPx↑,
*AChE↓, TQ exhibited the highest AChEI activity of 53.7 g/mL in which NS extract overall exhibited 84.7 g/mL, which suggests a significant AChE inhibition.
*cognitive↑, Most prominently, TQ has been found to regulate neurite maintenance for cognitive benefits by phosphorylating and thereby activating the MAPK protein, particularly the JNK proteins for embryogenesis and also lower the expression levels of BAX
*MAPK↑,
*JNK↑,
*BAX↓,
*memory↑, TQ portrays its potential of spatial memory enhancement by reversing the conditions as observed by MWM task
*Aβ↓, TQ thus, has been shown to ameliorate the Aβ accumulation
*MMP↑, improving the cellular activity, inhibiting mitochondrial membrane depolarization and suppressing ROS

2093- TQ,    Regulation of NF-κB Expression by Thymoquinone; A Role in Regulating Pro-Inflammatory Cytokines and Programmed Cell Death in Hepatic Cancer Cells
- in-vitro, Liver, HepG2 - in-vitro, Nor, NA
TumCD↑, evidence of the cytotoxic effects of TQ on HepG2 cells
selectivity↑, These findings indicate the selective regulation of HepG2 cell proliferation by TQ treatment without the detectable toxic effect of the normal hepatocytes
Casp3↑, TQ mediates the activation of Casp3, DLC1, and NF-κB, providing a new function of TQ in treating hepatocellular carcinoma (HCC).
DLC1↑,
NF-kB↑,
LDH↑, relative LDH production increased significantly in HepG2 cells treated with 500 ug/m
*toxicity↓, normal hepatocyte cells showed negligible differentiation in cell viability rate


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis

LDH↑, 1,  

Cell Death

Akt↑, 1,   Apoptosis↑, 1,   Casp3↑, 1,   TumCD↑, 1,  

Cell Cycle & Senescence

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

PI3K↓, 1,   TumCG↓, 1,  

Migration

DLC1↑, 1,  

Angiogenesis & Vasculature

angioG↓, 1,  

Immune & Inflammatory Signaling

NF-kB↑, 1,  

Drug Metabolism & Resistance

selectivity↑, 1,  

Clinical Biomarkers

LDH↑, 1,  

Functional Outcomes

AntiCan↑, 1,  
Total Targets: 14

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   Catalase↑, 2,   GPx↑, 2,   GSH↑, 1,   GSR↑, 1,   H2O2↓, 1,   HO-1↑, 1,   lipid-P↓, 2,   MDA↓, 2,   NRF2↑, 2,   ROS↓, 2,   SOD↑, 1,   TAC↑, 1,  

Mitochondria & Bioenergetics

MMP↑, 1,  

Core Metabolism/Glycolysis

BUN↓, 1,   cMyc↓, 1,   LDH↓, 2,  

Cell Death

BAX↓, 1,   Casp3↓, 1,   iNOS↑, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 1,   p38↓, 1,  

Cell Cycle & Senescence

cycD1/CCND1↓, 1,  

Migration

MMP9↓, 1,   TGF-β↓, 1,   TumCI↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature

VEGF↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   CRP↓, 1,   IL10↑, 1,   IL12↓, 1,   IL1β↓, 2,   IL6↓, 1,   Inflam↓, 1,   MyD88↓, 1,   NF-kB↓, 2,   TLR2↓, 1,   TLR4↓, 1,   TRIF↓, 1,  

Synaptic & Neurotransmission

AChE↓, 2,  

Protein Aggregation

Aβ↓, 1,  

Clinical Biomarkers

CRP↓, 1,   IL6↓, 1,   LDH↓, 2,  

Functional Outcomes

cardioP↑, 1,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 1,   RenoP↑, 2,   toxicity↓, 1,  

Infection & Microbiome

IRF3↓, 1,  
Total Targets: 55

Scientific Paper Hit Count for: LDH, Lactate Dehydrogenase
3 Thymoquinone
1 5-fluorouracil
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#:162  Target#:906  State#:%  Dir#:%
wNotes=on sortOrder:rid,rpid

 

Home Page