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| Ginkgo biloba from an ancient tree. Ginkgo biloba leaf extracts (commonly standardized as EGb 761, ~24% flavonol glycosides and ~6% terpene lactones) are best known for antioxidant, anti-inflammatory, platelet-activating factor (PAF) antagonism, and neurovascular effects. In preclinical cancer models, Ginkgo constituents have been associated with modulation of NF-κB, Nrf2, MAPK, and PI3K/AKT pathways, along with effects on cell cycle, apoptosis, and angiogenesis. Clinical oncology evidence is limited and heterogeneous. Important safety considerations include antiplatelet effects (bleeding risk) and CYP/P-gp interactions (product- and dose-dependent). GBE contains over 60 biologically active substances, the most important of which are terpentins, flavonoids, carboxylic acids, and L-ascorbic acid.
Ginkgo biloba
│
├── Ginkgo biloba leaf / generic GBE
│
├── Standardized extracts
│ └── EGb 761
│
├── Terpene lactones
│ ├── Ginkgolide A
│ ├── Ginkgolide B ← separate product
│ ├── Ginkgolide C
│ └── Bilobalide
│
├── Biflavonoids
│ ├── Ginkgetin ← separate product
│ ├── Isoginkgetin
│ ├── Bilobetin
│ ├── Sciadopitysin
│ └── Amentoflavone
│
├── Flavonols
│ ├── Quercetin
│ ├── Kaempferol
│ └── Isorhamnetin
│
└── Alkylphenolic acids
└── Ginkgolic acids ← separate product
**Issue with EGb761(Tebonin) vs other extracts:
| Feature | EGb 761 | Typical Amazon.ca Ginkgo |
| ----------------------- | ------------------------------------ | --------------------------------- |
| Source | Dried Ginkgo leaves | Usually dried leaves |
| Flavone glycosides | ~24% | Often 24%, sometimes unspecified |
| Terpene lactones | ~6% | Sometimes 6%; often not stated |
| Ginkgolides A/B/C | Controlled profile | Usually not individually verified |
| Bilobalide | Controlled profile | Usually not stated |
| Ginkgolic acids | **<5 ppm** | Frequently not stated |
| Extract/process | Defined proprietary process | Manufacturer-specific |
| Batch consistency | Pharmaceutical-style standardization | Variable |
| Human dementia evidence | Extensive | Usually indirect extrapolation |
| Equivalent to EGb 761? | Yes | **Not automatically** |
** Ginkgolic Acids can have associated risks of liver and kidney damage
nutridom claims EGb 761 equivalent formulation-Ginkgo can inhibit platelet aggregation(debateable) -Scavenges free radicals; reduces oxidative stress in neuronal cells -Suppresses pro-inflammatory cytokines (e.g., TNF-α, IL-1β). -Enhances microcirculation and oxygen delivery to brain tissues. -Reduces Aβ plaque formation and associated neurotoxicity. -May improve memory, attention, and processing speed in early-stage AD. Ginkgo biloba — a medicinal tree whose pharmacologically relevant preparations are primarily standardized extracts of dried leaves. It is classified as a botanical/herbal medicinal product rather than a single-molecule drug. Common abbreviations include GBE or GLE for Ginkgo biloba leaf extract; EGb 761 is a specific, extensively studied standardized extract containing approximately 24% flavonol glycosides and 6% terpene lactones, principally ginkgolides and bilobalide. Standardized medicinal extracts should be distinguished from crude leaf, seeds, and isolated ginkgolic acids; ginkgolic acids are potentially toxic constituents that are substantially removed during manufacture of high-quality standardized extracts. Neurocognitive and vascular evidence is substantially stronger than evidence for anticancer use. Primary mechanisms (ranked):
Bioavailability / PK relevance: Ginkgo leaf extract is a multicomponent preparation rather than a concentration-defined single compound. Terpene lactones including ginkgolides A, B and C and bilobalide reach systemic circulation after oral standardized extracts, while flavonoid glycosides undergo extensive metabolism to conjugated metabolites. Extract composition strongly affects pharmacology. At recommended standardized-extract doses around 120–240 mg/day, clinically important CYP-mediated interactions appear substantially smaller than suggested by many high-concentration in-vitro experiments, although medication interactions remain possible. In-vitro vs systemic exposure relevance: Many anticancer experiments use whole extracts or isolated flavonoids at concentrations considerably above concentrations achievable for the corresponding unconjugated constituents after ordinary oral Ginkgo supplementation. Cancer-cell findings involving isolated ginkgolic acid should not be treated as equivalent to effects of medicinal EGb 761 because standardized extracts intentionally contain very little ginkgolic acid. Consequently, direct extrapolation of most cancer-cell cytotoxicity studies to oral Ginkgo use is weak. Clinical evidence status: Cancer: preclinical only; no established anticancer efficacy and no validated role as cancer therapy. Dementia: human RCT evidence exists, particularly for standardized EGb 761 at 240 mg/day; the 2026 Cochrane assessment concludes that patients with dementia may obtain small-to-moderate improvements in global status, cognition and activities of daily living at approximately six months, while evidence for mild cognitive impairment shows little or no benefit. Ginkgo does not prevent dementia in cognitively normal older adults or those with MCI. It should therefore be regarded as a possible symptomatic adjunct in established dementia rather than a demonstrated disease-preventing or disease-modifying therapy. Safety / formulation constraint: Standardized leaf extract is generally tolerated at medicinal doses, but headache, dizziness and gastrointestinal effects occur. Bleeding events have been reported, and regulatory authorities advise caution or avoidance with anticoagulants, other products affecting coagulation, and around surgery. Pregnancy is contraindicated under the EMA medicinal-use monograph because platelet aggregation may be impaired. Raw or inadequately processed Ginkgo preparations are not interchangeable with standardized medicinal extracts. High-dose animal carcinogenicity findings exist for a non-EGb-761 Ginkgo extract, but their relevance to standard human medicinal dosing remains uncertain. Ginkgo biloba — Cancer-Relevant Mechanisms
TSF: P: 0–30 min R: 30 min–3 hr G: >3 hr Ginkgo biloba — Alzheimer’s disease: AD and dementia are substantially more clinically relevant indications for standardized Ginkgo leaf extract than cancer. EGb 761 has antioxidant, mitochondrial, vascular, anti-inflammatory and neuroprotective actions and has been studied in multiple randomized dementia trials. The most current high-level evidence indicates possible small-to-moderate symptomatic benefit in established dementia at approximately six months, but little or no benefit in mild cognitive impairment and no demonstrated prevention of incident Alzheimer’s disease. The evidence therefore supports classification as a possible symptomatic adjunct rather than a proven disease-modifying AD treatment. Primary mechanisms (ranked):
Clinical evidence status: RCT-supported symptomatic effect in established dementia, but heterogeneous and generally modest; little or no demonstrated benefit for MCI and no established dementia-prevention effect. Most positive modern trials evaluated specific standardized extracts, particularly EGb 761 at 240 mg/day, so results should not automatically be extrapolated to arbitrary commercial Ginkgo products. Ginkgo biloba — Alzheimer’s Disease Mechanisms
TSF: P: 0–30 min R: 30 min–3 hr G: >3 hr |
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| 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
|
| - | vitro+vivo, | NSCLC, | NA |
| 7211- | GBE, | Ginkgo Biflavones Cause p53 Wild-Type Dependent Cell Death in a Transcription-Independent Manner of p53 |
| - | in-vitro, | CRC, | HCT116 |
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#:89 Target#:275 State#:% Dir#:2
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