Ginkgolide B / N-cadherin Cancer Research Results

GGB, Ginkgolide B: Click to Expand ⟱
Features:

Ginkgolide B — a naturally occurring diterpene trilactone and one of the principal terpene lactones of Ginkgo biloba. It is a chemically defined small molecule, commonly abbreviated GB, GGB, GKB, and historically BN 52021. Its best-established pharmacological identity is as a potent competitive antagonist of the platelet-activating factor receptor (PAFR). Ginkgolide B is present in standardized Ginkgo extracts such as EGb 761 but is pharmacologically distinct from whole Ginkgo extract, ginkgetin, other biflavonoids, bilobalide, and ginkgolic acids. Its cancer evidence remains preclinical, with the strongest recurring theme being interference with PAF/PAFR-dependent tumor signaling and chemotherapy resistance.

Primary mechanisms (ranked):

  1. PAF receptor antagonism, suppressing PAF/PAFR-dependent inflammatory, survival, stemness, metastatic, and chemotherapy-resistance signaling.
  2. PAFR/NF-κB suppression, reducing pro-survival signaling and increasing chemotherapy sensitivity, particularly to gemcitabine and cisplatin in experimental cancer models.
  3. Antiproliferative and cell-cycle effects, including p21/p27 induction, cyclin D1 suppression, and G0/G1-S or related cell-cycle blockade in susceptible tumor cells.
  4. Apoptosis induction through caspase activation, BAX/Bcl-2-family modulation, and loss of tumor-cell survival signaling.
  5. Suppression of EMT, migration, and invasion through context-dependent regulation of ZEB1, miR-223-3p, PI3K/AKT/mTOR, and epithelial/mesenchymal markers.
  6. Suppression of cancer-stem-cell phenotypes through blockade of PAF/PAFR signaling, demonstrated particularly in ovarian-cancer models.
  7. Pyroptosis induction with GSDMD activation in gastric-cancer models, associated with inhibition of PI3K/AKT/mTOR signaling; currently a recent and less independently replicated mechanism.
  8. TSPO/PBR suppression in aggressive breast-cancer models, associated with cytostatic effects and reduced xenograft growth.
  9. Immune-microenvironment modulation through PAFR-dependent pathways, including emerging SREBP1/KLK8/CCL22-related effects in oral squamous-cell carcinoma.

Bioavailability / PK relevance: Ginkgolide B is systemically bioavailable in humans after oral standardized Ginkgo preparations, and human pharmacokinetic studies confirm measurable circulating Ginkgolide B. Its circulating lactone undergoes reversible hydrolysis to carboxylated forms, which have lower PAF-antagonist potency than the parent trilactone. Renal elimination is important. Direct intravenous studies of isolated Ginkgolide B in healthy subjects have used approximately 20–60 mg doses and demonstrate dose-related systemic exposure. Therefore, unlike many poorly characterized phytochemicals, Ginkgolide B has genuine human PK data; however, the exposure required for anticancer activity has not been clinically established.

In-vitro vs systemic exposure relevance: Cancer experiments commonly use isolated Ginkgolide B in the tens to hundreds of micromolar range, with some studies using approximately 100 µM or higher. These exposures should not be assumed achievable from ordinary oral Ginkgo supplements. Intravenous Ginkgolide B can produce substantially greater systemic exposure than oral extract, but no human anticancer exposure-response relationship has been established. Human PK therefore supports systemic availability but does not validate the concentrations used in cancer-cell experiments.

Clinical evidence status: Preclinical for cancer. Evidence includes cell culture, xenograft, chemotherapy-resistance, cancer-stem-cell, migration/invasion, and tumor-microenvironment studies. No established human anticancer trial or approved anticancer indication for isolated Ginkgolide B was identified. Direct Ginkgolide B injection is undergoing human pharmacokinetic and tolerability investigation for non-cancer indications, while standardized Ginkgo preparations provide extensive human exposure data. PAF antagonism may affect platelet biology, so concomitant anticoagulant or antiplatelet therapy remains an important clinical safety consideration even though bleeding effects cannot be extrapolated quantitatively from isolated Ginkgolide B experiments.

Ginkgolide B Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 PAF PAFR signaling PAFR signaling ↓; tumor survival ↓; stemness ↓; migration ↓; chemoresistance ↓ PAFR signaling ↓; platelet activation ↓; inflammatory activation ↓ P, R, G Central pharmacological mechanism PAFR antagonism is the best-established direct molecular action of Ginkgolide B and provides a biologically coherent link between inflammation, tumor progression, cancer stemness, and treatment resistance.
2 PAFR NF-κB survival signaling NF-κB activation ↓; survival signaling ↓; chemotherapy sensitivity ↑ NF-κB inflammatory signaling ↓ (context-dependent) R, G Chemosensitization and survival suppression PAFR blockade increases gemcitabine sensitivity in pancreatic-cancer cells and modifies cisplatin resistance in oral-cancer models. Mechanistically stronger than many downstream pathways because it derives from the established pharmacological target of Ginkgolide B.
3 Cell-cycle and proliferative signaling p21 ↑; p27 ↑; cyclin D1 ↓; proliferation ↓; cell-cycle arrest ↑ Generally less cytotoxic in tested normal cells G Cytostatic growth inhibition Ovarian-cancer studies demonstrate substantial proliferation inhibition at high micromolar exposure. Earlier ovarian studies also indicate G0/G1-to-S cell-cycle blockade.
4 Caspase and mitochondrial apoptosis Cleaved caspase-3 ↑; cleaved caspase-8 ↑; BAX ↑; Bcl-2 ↓; apoptosis ↑ Apoptosis generally ↓ in stressed neural and cardiovascular cells R, G Programmed tumor-cell death Direction is strongly context-dependent. Ginkgolide B may promote apoptosis in tumor cells while protecting stressed normal neural or cardiovascular cells from apoptotic injury.
5 Cancer stemness CSC phenotype ↓; spheroid formation ↓; tumor initiation ↓ Not established G Cancer stem-cell suppression PAF promotes ovarian-cancer stemness, while Ginkgolide B antagonism of PAFR suppresses CSC properties and reduces tumor growth in experimental models.
6 EMT and ZEB1 signaling EMT ↓; migration ↓; invasion ↓; ZEB1 ↓ (model-dependent); E-cadherin ↑; N-cadherin ↓ Not established G Metastatic phenotype suppression Supported in bladder and gastric-cancer models. The bladder-cancer literature implicates miR-223-3p-associated regulation of ZEB1; directionality reported within that paper should be interpreted at the protein-regulation level rather than generalized to all cancers.
7 PI3K AKT mTOR signaling PI3K ↓; AKT ↓; mTOR ↓ AKT ↑ in some stressed normal cells (context-dependent) R, G Survival and EMT suppression Reported prominently in recent gastric-cancer work. In normal endothelial, cardiac, or neural injury models Ginkgolide B can instead activate AKT-mediated survival pathways, making this strongly cell-context dependent.
8 Pyroptosis and GSDMD GSDMD ↑; pyroptosis ↑ Pyroptotic inflammation generally ↓ in neuroinflammatory models (context-dependent) G Inflammatory tumor-cell death Recent gastric-cancer evidence links Ginkgolide B to increased pyroptosis alongside PI3K/AKT/mTOR suppression. Independent replication remains limited.
9 TSPO peripheral benzodiazepine receptor TSPO expression ↓; proliferation ↓ Not established G Cytostatic tumor suppression An independent U.S. study demonstrated reduced TSPO expression and growth of aggressive MDA-MB-231 breast-cancer cells and xenografts. Historically TSPO was termed the peripheral-type benzodiazepine receptor.
10 Tumor immune microenvironment SREBP1 KLK8 CCL22 signaling ↓ (model-dependent); immunosuppressive recruitment ↓ Not established G Immune-microenvironment modulation Emerging oral-cancer evidence suggests Ginkgolide B can modify tumor-associated immune signaling. This is promising but considerably less replicated than PAFR antagonism.
11 Chemosensitization Gemcitabine sensitivity ↑; cisplatin sensitivity ↑ Normal-tissue selectivity incompletely established G Reduction of drug resistance Experimental pancreatic, ovarian, and oral-cancer studies support chemotherapy sensitization. No human oncology trial has established a clinically useful combination dose.
12 Clinical Translation Constraint Effective experimental concentrations often high; clinical anticancer exposure unknown PAF-dependent platelet function ↓; systemic PK established G Exposure and clinical-validation constraint Human oral and intravenous PK is documented, but cancer-active concentrations and therapeutic windows are unknown. Antiplatelet pharmacology and treatment interactions require consideration. No established clinical anticancer efficacy exists.

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



Alzheimer’s disease relevance: Ginkgolide B has meaningful preclinical evidence for neuroprotection in Alzheimer’s disease models. Reported actions include suppression of Aβ-induced microglial activation and neurotoxicity, inhibition and autophagic degradation of the NLRP3 inflammasome, reduced inflammatory caspase-1 signaling, enhancement of autophagic clearance of phosphorylated tau, increased BDNF-associated neuronal survival, and improvement of learning and memory in animal models. These effects contrast with several cancer mechanisms: AKT and cytoprotective signaling may increase in stressed neural cells, while apoptosis, oxidative stress, and inflammatory signaling decrease. No clinical efficacy of isolated Ginkgolide B for Alzheimer’s disease has been established.

Clinical evidence status: Preclinical for isolated Ginkgolide B. Human studies of Ginkgo extracts cannot be treated as direct clinical evidence for purified Ginkgolide B because extracts contain multiple terpene lactones and flavonoids.

Alzheimer’s disease relevance: Ginkgolide B has meaningful preclinical evidence for neuroprotection in Alzheimer’s disease models. Reported actions include suppression of Aβ-induced microglial activation and neurotoxicity, inhibition and autophagic degradation of the NLRP3 inflammasome, reduced inflammatory caspase-1 signaling, enhancement of autophagic clearance of phosphorylated tau, increased BDNF-associated neuronal survival, and improvement of learning and memory in animal models. These effects contrast with several cancer mechanisms: AKT and cytoprotective signaling may increase in stressed neural cells, while apoptosis, oxidative stress, and inflammatory signaling decrease. No clinical efficacy of isolated Ginkgolide B for Alzheimer’s disease has been established.

Clinical evidence status: Preclinical for isolated Ginkgolide B. Human studies of Ginkgo extracts cannot be treated as direct clinical evidence for purified Ginkgolide B because extracts contain multiple terpene lactones and flavonoids.

Ginkgolide B Alzheimer’s-Relevant Mechanisms

Rank Pathway / Axis AD Modulation TSF Primary Effect Notes / Interpretation
1 Amyloid beta neurotoxicity Aβ-induced neurotoxicity ↓; neuronal survival ↑ R, G Neuroprotection Direct protection from Aβ-mediated neuronal and microglial toxicity has been demonstrated experimentally.
2 NLRP3 inflammasome NLRP3 activation ↓; caspase-1 ↓; neuroinflammation ↓ R, G Inflammasome suppression Multiple experimental studies support inhibition of Aβ-associated NLRP3 signaling. Autophagic degradation of NLRP3 has also been reported.
3 Microglial activation Microglial activation ↓; inflammatory cytokines ↓ R, G Reduced neuroinflammation PAFR antagonism and downstream inflammatory suppression are mechanistically consistent with reduced microglia-mediated neuronal injury.
4 Tau autophagic clearance Autophagy ↑; phosphorylated tau degradation ↑; p-Tau ↓ G Proteostasis improvement Experimental studies comparing EGb 761 constituents identify Ginkgolide B as capable of increasing autophagic degradation of phosphorylated tau.
5 BDNF neuronal survival BDNF ↑; neuronal survival ↑; apoptosis ↓ G Synaptic and neuronal protection Ginkgolide B protects hippocampal neurons from Aβ-associated apoptosis partly through increased BDNF signaling.
6 Oxidative and mitochondrial stress ROS ↓; mitochondrial dysfunction ↓; Cyt-c release ↓; apoptosis ↓ R, G Cellular stress protection Common neuroprotective pattern across Aβ and other neural-injury models; contrasts with pro-death effects observed in some cancer cells.
7 Cognitive function Learning ↑; memory ↑ G Functional improvement Reported in animal neurodegeneration models; no validated clinical cognitive benefit can presently be attributed specifically to isolated Ginkgolide B.
8 Clinical Translation Constraint Human exposure established; isolated Ginkgolide B efficacy unproven G Clinical-evidence limitation Human Ginkgo-extract studies cannot establish efficacy of purified Ginkgolide B. Brain exposure, optimal dose, and long-term therapeutic window remain incompletely defined.

TSF: P: 0–30 min     R: 30 min–3 hr     G: >3 hr
N-cadherin, N-cadherin: Click to Expand ⟱
Source:
Type:
Also known as Cadherin2 (CDH2).
N-cadherin is a type of cell adhesion molecule that plays a crucial role in the development and maintenance of tissue structure. In the context of cancer, N-cadherin has been implicated in the progression and metastasis of various types of tumors.
N-cadherin expression is increased in various types of cancer.
Normally, N-cadherin is expressed in mesenchymal cells, such as fibroblasts and smooth muscle cells. However, in cancer cells, N-cadherin expression is often upregulated, which can contribute to the epithelial-to-mesenchymal transition (EMT). EMT is a process by which epithelial cells acquire a more mesenchymal phenotype, which is characterized by increased motility, invasiveness, and resistance to apoptosis.
The expression of N-cadherin in cancer cells is closely associated with tumorigenesis and metastasis. Additionally, the soluble N-cadherin level in the serum of cancer patients is much higher than that in the serum of healthy patients, revealing a positive relation with poor prognosis.
Scientific Papers found: Click to Expand⟱
7201- GGB,    Ginkgolide B Inhibits EMT and Promotes Pyroptosis in Gastric Cancer via AKT/mTOR Pathway
- vitro+vivo, GC, AGS - in-vitro, GC, HGC27
TumCI↓, TumCMig↓, Apoptosis↑, Pyro↑, BAX↑, GSDMD↑, Bcl-2↓, TumCG↓, EMT↓, PCNA↓, N-cadherin↓, E-cadherin↑, PI3K↓, Akt↓, mTOR↓, Dose↝,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   GSDMD↑, 1,   Pyro↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

PCNA↓, 1,  

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

EMT↓, 1,   mTOR↓, 1,   PI3K↓, 1,   TumCG↓, 1,  

Migration(tgid=13) ⓘ

E-cadherin↑, 1,   N-cadherin↓, 1,   TumCI↓, 1,   TumCMig↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,  
Total Targets: 16

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: N-cadherin, N-cadherin
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#:439  Target#:355  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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