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| Apigenin — a plant-derived flavone (4′,5,7-trihydroxyflavone) abundant in parsley/celery/chamomile and other dietary sources, often abbreviated APG (or “Api” in some indexes). It is a small-molecule polyphenol classified as a dietary phytochemical/nutraceutical candidate with broad pleiotropic signaling effects in oncology models (cell-cycle control, apoptosis, inflammatory signaling, metabolic stress, and invasion/angiogenesis programs), but with important translation constraints driven by low aqueous solubility and extensive phase-II conjugation. Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral apigenin exposure is commonly limited by poor water solubility and extensive first-pass metabolism (glucuronidation/sulfation). Human data indicate circulating apigenin is largely present as conjugated metabolites, and dietary intake can yield only low (typically sub-µM) systemic levels; lipidic/self-emulsifying formulations can increase exposure in vivo (formulation-dependent). Reported half-life/kinetic parameters vary widely across studies and matrices. In-vitro vs systemic exposure relevance: Many anti-cancer in vitro studies use ~10–50+ µM apigenin, which can exceed typical achievable free aglycone systemic levels after oral intake; some effects may therefore be high-concentration or formulation-enabled rather than diet-achievable. Tissue-local exposure (GI lumen, local mucosa) may be higher than plasma, and conjugate biology may contribute (context-dependent). Clinical evidence status: Predominantly preclinical oncology evidence (cell and animal models) with limited, non-definitive human cancer interventional data; at least one pilot clinical study concept exists/has been registered (status-dependent). Strongest human evidence base is for non-cancer indications and general bioactivity rather than oncology efficacy. Apigenin present in parsley, celery, chamomile, oranges and beverages such as tea, beer and wine."It exhibits cell growth arrest and apoptosis in different types of tumors such as breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach, by modulating several signaling pathways." -Note half-life reports vary 2.5-90hrs?. -low solubility of apigenin in water : BioAv (improves when mixed with oil/dietary fat or lipid based formulations) -best oil might be MCT oils (medium-chain fatty acids) Pathways: - Often considered an antioxidant, in cancer cells it can paradoxically induce ROS production (one report that goes against most others, by lowering ROS in cancer cells but still effective) - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, UPR↑, cl-PARP↑, HSP↓ - Lowers AntiOxidant defense in Cancer Cells: NRF2↓, GSH↓ (Conflicting evidence about Nrf2) - Combined with Metformin (reduces Nrf2) amplifies ROS production in cancer cells while sparing normal cells. - Raises AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑">Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : , MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, 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↓, TumCI↓, FAK↓, ERK↓, - inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, PDK1↓, GLUT1↓, LDHA↓, HK2↓, Glucose↓, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, PDGF↓, EGFR↓, Integrins↓, - inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, GLi↓, GLi1↓, - Others: PI3K↓, AKT↓, JAK↓, 1, 2, 3, STAT↓, 1, 2, 3, 4, 5, 6, Wnt↓, β-catenin↓, AMPK↓,, α↓,, ERK↓, 5↓, JNK↓, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol). - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes) -Ex: other flavonoids(chrysin, Luteolin, querectin) curcumin, metformin, sulforaphane, ASA Neuroprotective, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells Apigenin exhibits biological effects (anticancer, anti-inflammatory, antioxidant, neuroprotective, etc.) typically at concentrations roughly in the range of 1–50 µM. Parsley microgreens can contain up to 2-3 times more apigenin than mature parsley. Apigenin is typically measured in the range of 1-10 μM for biological activity. Assuming a molecular weight of 270 g/mol for apigenin, we can estimate the following μM concentrations: 10uM*5L(blood)*270g/mol=13.5mg apigenin (assumes 100% bioavailability) then an estimated 10-20 mg of apigenin per 100 g of fresh weight parlsey 2.2mg/g of apigenin fresh parsley 45mg/g of apigenin in dried parsley (wikipedia) so 100g of parsley might acheive 10uM blood serum level (100% bioavailability) BUT bioavailability is only 1-5% (Supplements available in 75mg liposomal)( Apigenin Pro Liposomal, 200 mg from mcsformulas.com) A study had 2g/kg bw (meaning 160g for 80kg person) delivered a maximum 0.13uM of plasma concentration @ 7.2hrs. Assuming parsley is 90-95% water, then that would be ~16g of dried parsley Conclusion: to reach 10uM would seem very difficult by oral ingestion of parsley. Other quotes: “4g of dried parsley will be enough for 50kg adult” 5mg/kg BW yields 16uM, so 80Kg person means 400mg (if dried parsley is 130mg/g, then would need 3g/d) In many cancer cell lines, concentrations in the range of approximately 20–40 µM have been reported to shift apigenin’s activity from mild antioxidant effects (or negligible ROS changes) toward a clear pro-oxidant effect with measurable ROS increases. Low doses: At lower concentrations, apigenin is more likely to exhibit its antioxidant properties, scavenging ROS and protecting cells from oxidative stress. In normal cells with robust antioxidant systems, apigenin’s antioxidant effects might prevail, whereas cancer cells—often characterized by an already high level of basal ROS—can be pushed over the oxidative threshold by increased ROS production induced by apigenin. In environments with lower free copper levels, this pro-oxidant activity is less pronounced, and apigenin may tilt the balance toward its antioxidant function. Apigenin — cancer-relevant mechanistic pathway matrix
TSF P: 0–30 min |
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| Caspases are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases. Caspase-1 may have both tumorigenic or antitumorigenic effects on cancer development and progression, but it depends on the type of inflammasome, methodology, and cancer. Catalase is an enzyme found in nearly all living cells exposed to oxygen. Its primary role is to protect cells from oxidative damage by catalyzing the conversion of hydrogen peroxide (H₂O₂), a potentially damaging byproduct of metabolism, into water (H₂O) and oxygen (O₂). This detoxification process is crucial because excess H₂O₂ can lead to the formation of reactive oxygen species (ROS) that damage proteins, lipids, and DNA. Catalase and Cancer Oxidative Stress and Cancer: Cancer cells often experience increased levels of oxidative stress due to rapid proliferation and metabolic changes. This stress can lead to DNA damage, promoting tumorigenesis. Catalase helps mitigate oxidative stress, and its expression can influence the survival and proliferation of cancer cells. Expression Levels in Different Cancers: Overexpression: In some cancers, such as breast cancer and certain types of leukemia, catalase may be overexpressed. This overexpression can help cancer cells survive in oxidative environments, potentially leading to more aggressive tumor behavior. Downregulation: Conversely, in other cancers, such as colorectal cancer, reduced catalase expression has been observed. This downregulation can lead to increased oxidative stress, contributing to tumor progression and metastasis. Prognostic Implications: Survival Rates: Studies have shown that high levels of catalase expression can be associated with poor prognosis in certain cancers, as it may enable cancer cells to resist apoptosis (programmed cell death) induced by oxidative stress. Some types of cancer cells have been reported to exhibit lower catalase activity, possibly increasing their vulnerability to oxidative damage under certain conditions. This vulnerability has even been exploited in some therapeutic strategies (for example, approaches that generate excess H₂O₂ or other ROS specifically targeting cancer cells have been researched). |
| 1562- | Api, | Apigenin protects human melanocytes against oxidative damage by activation of the Nrf2 pathway |
| - | in-vitro, | Vit, | NA |
| 1547- | Api, | Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading |
| - | Review, | NA, | NA |
| 2638- | Api, | Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between pro-apoptotic and pro-survival pathways to induce PEL cell death |
| - | in-vitro, | lymphoma, | PEL |
| 2317- | Api, | Apigenin intervenes in liver fibrosis by regulating PKM2-HIF-1α mediated oxidative stress |
| - | in-vivo, | Nor, | NA |
| 4280- | Api, | Protective effects of apigenin in neurodegeneration: An update on the potential mechanisms |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
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
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