Database Query Results : Propolis -bee glue, , LDH

PBG, Propolis -bee glue: Click to Expand ⟱

Features: Compound

Brazilian Green Propolis often considered best
• Derived from Baccharis dracunulifolia, this type is rich in artepillin C.
• It has been widely researched for its anticancer, anti-inflammatory, and antioxidant properties.
-Propolis common researched flavonoids :chrysin, pinocembrin, galangin, pinobanksin(Pinocembrin)
-most representative phenolic acids were caffeic acid, p-coumaric acid, and ferulic acid, as well as their derivatives, DMCA and caffeic acid prenyl, benzyl, phenylethyl (CAPE), and cinnamyl esters
-One of the most studied active compounds of a poplar-type propolis is caffeic acid phenethyl ester (CAPE)
-caffeic acid phenethyl ester (CAPE), galangin, chrysin, nemorosone, propolin G, artepillin C, cardanol, pinocembrin, pinobanksin, chicoric acid, and phenolic acids (caffeic acid, ferulic acid, and coumaric acid), as well as luteolin, apigenin, myricetin, naringenin, kaempferol, quercetin, polysaccharides, tannins, terpenes, sterols, and aldehydes -content highly variable based on location and extraction
Two main factors of interest:
1. affects interstitual fluild pH
2. high concentration raises ROS (Reactive Oxygen Species), while low concentration may reduce ROS

- Artepillin-C (major phenolic compounds found in Brazilian green propolis (BGP))
- caffeic acid major source

Propolis is chemically diverse (300+ compounds reported) and composition depends on botanical/geographic source.
Antibacterial activity is documented in classic literature (often stronger against Gram+).
CAPE from propolis has reported preferential tumor cytotoxicity in early landmark work (often cited in antimicrobial paper references)

Do not combine with 2DG

Pathways:
-Propolis compounds (e.g., artepillin C, caffeic acid phenethyl ester [CAPE]) can trigger apoptosis (programmed cell death) in cancer cells.
-Propolis has been shown to inhibit NF‑κB activation.
-Propolis extracts can cause cell cycle arrest at specific checkpoints (e.g., G0/G1 or G2/M phases).
-Enhance the body’s antitumor immune responses, for example by activating natural killer (NK) cells and modulating cytokine profiles.

-Note half-life no standard, high variablity of content.
BioAv poor water solubility, and low oral bioavailability.
Pathways:
- high concentration may induce ROS production, while low concentrations mya low it. This may apply to both normal and cancer cells. Normal Cells Example. (Also not sure if high level are acheivable in vivo due to bioavailability)
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓ -->
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : NLRP3↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, P53↑,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDH">LDHA↓, HK2↓, PFKs↓, PDKs↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓,
- Others: PI3K↓, AKT↓, STAT↓, β-catenin↓, AMPK, 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 / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	ROS / redox stress (context-selective)	Often ↑ ROS / oxidative stress susceptibility (P→R→G)	Often antioxidant / cytoprotective in inflammatory stress contexts (R→G)	P, R, G	Stress amplifier / selectivity gate	Net ROS direction is highly context- and extract-dependent; propolis chemistry varies by geography/plant source and can shift redox behavior.
2	NF-κB inflammatory transcription	↓ NF-κB activity (R→G)	Anti-inflammatory signaling in immune/tissue contexts (R→G)	R, G	Anti-inflammatory / anti-survival transcription	A common “hub” claim across propolis literature; contributes to reduced cytokine/pro-survival programs.
3	Intrinsic apoptosis (mitochondria → caspases)	↑ apoptosis; ↑ caspase activation (G)	↔ (usually less activation)	G	Cell death execution	Often downstream of sustained stress signaling and/or survival pathway suppression.
4	MAPK re-wiring (ERK / p38 / JNK)	Stress MAPK shifts; JNK/p38 often ↑ with stress (P→R); ERK variable	↔ / context-dependent	P, R, G	Signal reprogramming	MAPK directions depend on extract composition, dose, and tumor type; best described as “re-wiring” rather than fixed arrows for ERK.
5	PI3K → AKT (± mTOR)	↓ PI3K/AKT survival signaling (R→G)	↔	R, G	Growth/survival suppression	Often reported alongside reduced proliferation and increased apoptosis susceptibility.
6	Nrf2 / antioxidant response (HO-1, GSH enzymes)	Context-dependent (may be ↓ in tumor-stress settings; may be ↑ as adaptation)	Often ↑ protective antioxidant response under stress	R, G	Adaptive buffering	Nrf2 direction is not universal; avoid absolute “Nrf2 always ↑/↓” statements for propolis.
7	Angiogenesis (VEGF and related factors)	↓ angiogenic signaling outputs (G)	↔	G	Anti-angiogenic support	Usually shows up in later gene-expression / phenotype assays rather than early signaling.
8	EMT / invasion / migration (MMPs, EMT markers)	↓ EMT / ↓ migration & invasion programs (G)	↔	G	Anti-invasive phenotype	Often measured as reduced MMP activity and reduced migration/invasion phenotypes; timing tends to be later.
9	Antimicrobial / microbiome-relevant effects	Indirect (may reduce infection-driven inflammation)	Direct antimicrobial activity (context)	R, G	Host-protective / anti-infective	Propolis has documented antibacterial activity (stronger vs many Gram+ than Gram− in classic reports), which can matter for inflammation-linked biology.
10	Key bioactives (CAPE; flavonoids/phenolics)	CAPE-class compounds: tumor-selective cytotoxicity reported (G)	↔	G	“Active fraction” concept	Propolis is a mixture; effects may be driven by a few high-impact phenolics (e.g., CAPE) and vary by extract standardization.

Time-Scale Flag (TSF): P / R / G

P: 0–30 min (primary/physical–chemical effects; rapid signaling / phosphorylation shifts)
R: 30 min–3 hr (redox signaling + acute stress-response signaling)
G: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)

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⟱

1682-

PBG,

Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits

Review,

Var,

i-LDH↓, cytotoxic activities of Tualang honey in human breast cancer cells were demonstrated by elevated secretion of lactate dehydrogenase (LDH)
Akt↓, figure 2
MAPK↓, figure 2
NF-kB↓, figure 2
IL1β↓, figure 2
IL6↓, figure 2
TNF-α↓, figure 2
iNOS↓, figure 2
COX2↓, figure 2
ROS↓, figure 2
Bcl-2↓, figure 2
PARP↓, figure 2
P53↑, figure 2
BAX↑, figure 2
Casp3↑, figure 2
TumCCA↑, Several components of honey such as chrysin, quercetin, and kaempferol have been shown to arrest cell cycle at various phases such as G0/G1, G1, and G2/M
Cyt‑c↑, hese stimuli cause several proteins located within the intermembrane space (IMS) of the mitochondria, such as cytochrome c, to be released
MMP↓, Honey induces MOMP in cancer cell lines by decreasing the mitochondrial membrane potential
eff↑, amplifying the apoptotic effect of tamoxifen by intensified depolarization of the mitochondrial membrane.

2430-

PBG,

The cytotoxic effects of propolis on breast cancer cells involve PI3K/Akt and ERK1/2 pathways, mitochondrial membrane potential, and reactive oxygen species generation

in-vitro,

BC,

MDA-MB-231

TumCP↓, CP extract exhibited antiproliferative and cytotoxic effects on MDA MB-231 cells, what may be probably related to PI3K/Akt and ERK1/2 pathways.
TP53↓, decreased expression of apoptosis-related genes (TP53, CASP3, BAX and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, These results suggested that CP cytotoxic effects on MDA MB-231 cells might be associated with the intracellular ROS production
eff↓, CP-induced ROS generation was reduced after cotreatment with the antioxidant NAC, which increased the percentage of viable cells, suggesting that CP-induced necrotic-related cell death could be associated with ROS production
MMP↓, Necrosis death is associated with mitochondrial dysfunction and our propolis sample reduced the MMP and increased LDH levels.
LDH↑,
ATP↓, rupture of mitochondrial membrane, loss of adenosine triphosphate (ATP),
Ca+2↑, excessive ROS production, intracellular [Ca+2] elevation, osmotic shock,

1663-

PBG,

Propolis and Their Active Constituents for Chronic Diseases

Review,

Var,

NF-kB↓, CAPE (a bioactive constituent of propolis) was reported to have anticancer properties by inhibiting NF-κB, caspase and Fas signaling activation in MCF-7 cells
Casp↓,
Fas↓,
DNAdam↑, DNA fragmentation, CCAAT/enhancer binding protein homologous protein expression and caspase-3 activity
Casp3↑,
P53↝, Chinese propolis (EECP) and its bioactive constituents mainly persist due to regulation of the annexin A7 and p53 proteins, mitochondrial membrane potential and ROSs, as well as that inhibition of NF-κB causes apoptosis in cancer cells
MMP↝,
ROS↑, Herrera et al. and reported on the MDA-MB 231 tumor cell line, and the inhibitory effect of propolis was proposed to occur through the induction of mitochondrial dysfunction, resulting in ROS-associated necrosis
mtDam↑,
Dose?, A concentration of 100 μg/mL was able to attain 71% cytotoxicity
angioG↓, negative effect on angiogenesis, proliferation and migration of tumor cells. A concentration of 25–200 μg/mL noticeably inhibited the metastasis of breast cancer
TumCP↓,
TumCMig↓,
BAX↑,
selectivity↑, Negligible effect in fibroblasts
MMP↓, Cuban: Disturbed the mitochondrial potential, lactate dehydrogenase released, production of ROS and cell migration
LDH↓,
IL6↓, Chinese: Decreased cell tube generation, IL-6, IL-1β, TNF-α-like inflammatory mediators, glycolytic enzymes and mitochondrial potential. Promoted ROS generation
IL1β↓,
TNF-α↓,

1672-

PBG,

The Potential Use of Propolis as an Adjunctive Therapy in Breast Cancers

Review,

BC,

ChemoSen↓, 4 human clinical trials that demonstrated the successful use of propolis in alleviating side effects of chemotherapy and radiotherapy while increasing the quality of life of breast cancer patients, with minimal adverse effects.
RadioS↑,
Inflam↓, immunomodulatory, anti-inflammatory, and anti-cancer properties.
AntiCan↑,
Dose∅, Indonesia: IC50 = 4.57 μg/mL and 10.23 μg/mL
mtDam↑, Poland: propolis induced mitochondrial damage and subsequent apoptosis in breast cancer cells.
Apoptosis?,
OCR↓, China: CAPE inhibited mitochondrial oxygen consumption rate (OCR) by reducing basal, maximal, and spare respiration rate and consequently inhibiting ATP production
ATP↓,
ROS↑, Iran: inducing intracellular ROS production, IC50 = 65-96 μg/mL
ROS↑, Propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating the occurrence of ROS-associated necrosis.
LDH↓,
TP53↓, Interestingly, a reduced expression of apoptosis-related genes such as TP53, CASP3, BAX, and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, CAPE: inducing oxidative stress through upregulation of e-NOS and i-NOS levels
eNOS↑,
iNOS↑,
eff↑, The combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone
hTERT/TERT↓, downregulation of the mRNA levels of hTERT and cyclin D1
cycD1/CCND1↓,
eff↑, Synergism with bee venom was observed
eff↑, Statistically significant decrease was found in the MCF-7 cell viability 48 h after applying different combinations of cisplatin (3.12 μg/mL) and curcumin (0.31 μg/mL) and propolis (160 μg/mL)
eff↑, Nanoparticles of chrysin had significantly higher cytotoxicity against MCF-7 cells, compared to chrysin
eff↑, Propolis nanoparticles appeared to increase cytotoxicity of propolis against MCF-7 cells
STAT3↓, Chrysin also inhibited the hypoxia-induced STAT3 tyrosine phosphorylation suggesting the mechanism of action was through STAT3 inhibition.
TIMP1↓, Propolis reduced the expression of TIMP-1, IL-4, and IL-10.
IL4↓,
IL10↓,
OS↑, patients supplemented with propolis had significantly longer median disease free survival time (400 mg, 3 times daily for 10 d pre-, during, and post)
Dose∅, 400 mg, 3 times daily for 10 d pre-, during, and post
ER Stress↑, endoplasmic reticulum stress
ROS↑, upregulating the expression of Annexin A7 (ANXA7), reactive oxygen species (ROS) level, and NF-κB p65 level, while simultaneously reducing the mitochondrial membrane potential.
NF-kB↓,
p65↓,
MMP↓,
TumAuto↑, propolis induced autophagy by increasing the expression of LC3-II and reducing the expression of p62 level
LC3II↑,
p62↓,
TLR4↓, propolis downregulates the inflammatory TLR4
mtDam↑, propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating ROS-associated necrosis in MDA MB-231cancer cells
LDH↓,
ROS↑,
Glycolysis↓, inhibit the proliferation of MDA-MB-231 cells by targeting key enzymes of glycolysis, namely glycolysis-hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA),
HK2↓,
PFK↓,
PKM2↓,
LDH↓,
IL10↓, propolis significantly reduced the relative number of CD4+, CD25+, FoxP3+ regulatory T cells expressing IL-10
HDAC8↓, Chrysin, a propolis bioactive compound, inhibits HDAC8
eff↑, combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone.
eff↑, Propolis also upregulated the expression of catalase, HTRA2/Omi, FADD, and TRAIL-associated DR5 and DR4 which significantly enhanced the cytotoxicity of doxorubicin in MCF-7 cells
P21↑, Chrysin, a propolis bioactive compound, inhibits HDAC8 and significantly increases the expression of p21 (waf1/cip1) in breast cancer cells, leading to apoptosis.

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

AntiCan↑, 1, OS↑, 1,
Total Targets: 74

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: LDH, Lactate Dehydrogenase

4 Propolis -bee glue

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#:137  Target#:906  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Database Query Results : Propolis -bee glue, , LDH

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

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

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

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