The 14+ Benefits Of Amentoflavone

Amentoflavone Is Cool (AF) 😉

Amentoflavone (AF) is a naturally occurring biflavonoid found in many (over 120) natural plants, such as Gingko Biloba and St. John's Wort (AF found in Diet and Supplements can be found here). R

 
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Basics Of Amentoflavone

This polyphenolic compound (Amentoflavone) has multiple bioactivities on: R

  • Aging
  • Anxiety and Depression
  • Brain Disorders
  • Cancer
  • Diabetes
  • Heart Disease
  • Inflammation and Oxidation
  • Pain
  • Skin Disorders
 
 

Benefits Of Amentoflavone

1. Protects The Brain

 
 

Amentoflavone (AF) can protect against neuroinflammation. R R

Advanced Glycation End-products (AGEs) are associated with many pathogenic disorders such as Alzheimer's Disease (AD), diabetes, atherosclerosis, and cardiovascular diseases. R

AF is a potent inhibitor of AGE formation. R

AF may also prevent the development of AD by stopping amyloid-beta plaque formation and by inhibiting acetylcholinesterase (AChE), thus increasing the neurotransmitter Acetylcholine (ACh) in the brain. R R R R

AF may prevent the development of Parkinson's Disease (PD) by its ability to protect dopamine cells against toxins in the brain. R

AF may protect against excitotoxic damage to the brain induced by seizuresR

For example, AF given to animal models of epilepsy had better symptoms, less seizures, and shortened attack time, as well as reduced inflammation of the hippocampus vs control animals. R

Also in the hippocampus, AF can also protect against glutamate-induced oxidative stress by increasing glutathione in the brain. R

2. Has Anti-Oxidant and Anti-Inflammatory Properties

Oxidative stress is one major part of the inflammatory response. R

AF can protect cells against oxidative stress induced damage to the cell wall. R

It also protects against inflammation. R

For example, AF is able to protect against sepsis-associated acute lung injury by activating NRF2, thus increasing the antioxidant glutathione. R

AF also protects against high levels immune system stimulation. R

AF may also protect against damage from EMF radiation to the body. R

3. May Reduce Pain

By working on the inflammatory response, AF may help reduce pain. R

For example, AF can reduce inflammation and pain in arthritis. R

4. May Prevent Cancer Formation

 
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AF has anti-tumor properties. R R R R

One way it does this is by stopping the progression of the cancerous cycle mid-cycle and by inhibiting Vascular Endothelial Growth Factor (VEGF). R R

AF may protect against:

  • Bone Cancer R
  • Breast Cancer R R R
  • Cervical Cancer R R
  • Liver Cancer R R
  • Lung Cancer R R
  • Ovarian Cancer R
  • Skin Cancer R R

AF may combine well with chemotherapy drugs like doxorubicin and sorafenib to be more effective against cancer. R R

5. Helps With Depression And Anxiety

AF may help with depression by possibly acting on a 5-HT2 and adrenergic receptors receptors. R

For example, AF can inhibit binding at serotonin, dopamine, delta-opioid (DOR), kappa-opioid (KOR), and benzodiazepine receptors (BzRs). R

As a KOR antagonist, AF may help with opioid-induced depression. R

AF may eliminate anxiety by being an ionotropic GABA receptor agonist and binding (moderate) to GABA-alpha/beta receptors. R R R

This is because AF can cross the blood brain barrier and act (strong, biphasic, negative allosteric modulator of GABA) on the BzRs (similarly to the anti-anxiety drug diazepam). R R R

6. Protects The Gut And Microbiome

AF can protect the gut against inflammation from Ulcerative Colitis (UC). R

It may also protect against ulcer formation by alcohol and H. PyloriR R

AF may protect the immune system against lectins. R 

AF also may protect the gut microbiome. R

7. Protects Against Skin Aging And Inflammation

 
 

UVB can cause premature aging, especially to the skin. R

AF can protect skin cells from UVB-induced damage and aging. R R

Therefore, AF may act as a sunscreen alternative for when going out into the sun.

AF can also reduce scarring formation. R

By suppressing inflammatory cytokines (TH17), AF may benefit those with psoriasis. R

8. Has Antimicrobial Properties

AF has antibacterial activity against:

  • Escherichia coli R
  • Enterococcus faecium R
  • Pseudomonas aeruginosa R
  • Staphylococcus aureus R
  • Streptococcus mutans R
  • Streptococcus pneumoniae (protects against the toxin Pneumolysin) R

AF synergizes with the antibiotics Ampicillin, Cefotaxime, and Chloramphenicol. R

 AF has antifungal activity against:

  • Aspergillus fumigatus R
  • Candida albicans R R
  • Mycobacterium tuberculosis R
  • Saccharomyces cerevisiae R
  • Trichosporon beigelii R 

AF has anti-parasitic activity against:

  • Plasmodium falciparum (AF may help prevent malaria) R

AF has antiviral activity against:

    • Coronavirus (severe acute respiratory syndrome coronavirus) R
    • Coxsackievirus B3 R R
    • Dengue Virus R
    • HIV R
    • Respiratory Syncytial Virus R

    9. Improves The Vascular System

    AF can relax the vascular system and protect it from inflammation. R R R

    AF can also protect cells against hypoxia (lack of oxygen). R

    Cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) (cAMP-PDE) inhibitors have shown to protect the heart by enhancing its ability to contact. R

    AF is a PDE inhibitor and may help the vascular system by enhancing blood flow in the body. R

    This also allows for more cAMP levels, allowing the vascular system to have more energy. R

    10. May Improve Exercise Performance

    On top of increasing blood flow (as a PDE inhibitor), AF may help with exercise by enhancing calcium release in muscles (similar to caffeine). R

    11. Combats Diabetes And Obesity

     
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117752

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117752

     

    Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been used as a way to treat type 2 diabetes. R

    AF can inhibit PTP1B. R

    AF can also stabilize glucose, regulate insulin secretion, and restore signaling of the pancreas. R R

    AF can protect against high fat-induced metabolic dysfunction (dose dependently) by reducing fasting blood glucose levels, fasting insulin levels and HOMA-IR, and decreasing activity of PPAR-gamma expression. R

    This activity as well as AF's ability to inhibit fatty acid synthase (FASN) may help against obesity. R

    12. Protects The Liver And Metabolism

    AF can increase glutathione in the liver. R

    AF can protect the liver from dysregulation of cholesterol and triglyceride levels. R

    AF can reduce total triglyceride, total cholesterol, and LDL-C levels, while increasing "good" HDL-C levels. R

    It can also decrease levels of C-Reactive Protein (CRP) in the liver. R

    13. Promotes Bone Growth

    AF has an osteogenic effect on bones, helping enhance bone stem cells and bone repair. R

    14. May Prevent Hair Loss

    AF may inhibit prostaglandin D2 (PGD2), and thus may help prevent hair loss, without adverse skin reactions. R

    My Experience

    I’m currently trying Clubmoss, Tamanu, Gingko, MangosteenPili, and St. John's Wort.

    I will report back with my full data soon. 

    Natural Sources Of Amentoflavone

    Pure amentoflavone (AF) is pricey to manufacture, so it's best to get it in dietary or herbal sources

    AF may synergize with EGCG and Quercetin. R

    It may also synergize with adrenergic agonists.

     
     

    Diet:

    Herbs, Supplements, And Oils:

    Other:

    • Allanblackia monticola R
    • Amanoa almerindae R
    • Biota semipervirens R
    • Brazilian Pepper (may cause reactions) R
    • Caesalpinia pyramidalis R
    • Campylospermum calanthum R
    • Campylospermum mannii R
    • Casearia clarkei R
    • Celaenodendron mexicanum R
    • Chinese Yew R
    • China-fir R
    • Cnestis ferruginea R
    • Crowberry R
    • Currant-rhus R
    • Dacrydium araucarioides R
    • Discocleidion rufescens R
    • Dorstenia barteri R
    • Drypetes (Putranjivaceae) R R R
    • Galeobdolon chinense R
    • Hypericum connatum R
    • Karmelitter Geist R
    • Lanaria lanata R
    • Leylandii R
    • Little Tree Plant R
    • Luxemburgia nobilis R
    • Nana-berry R
    • Nandina domestica R
    • Nanuza plicata R
    • Ochna schweinfurthiana R
    • Ouratea R R R
    • Oyster Bay Pine R
    • Perah R
    • Pistacia chinensis R
    • Podocarpus imbricadus R
    • Rospigliosii R R
    • Struthiola argentea R
    • Tmesipteris tannensis R
    • Turnsole R
    • Wax Tree R

    Caveats

    Amentoflavone (AF) may increase heart rate (specifically the rate of heart beats). R

    AF can interact with many medications by being a potent inhibitor of CYP3A4 and CYP2C9, which are enzymes responsible for the metabolism of some drugs in the body. R

    Mechanism Of Action

    Simple:

    • Increases α1-adrenoceptor R
    • Increases α2-adrenoceptor R
    • Increases ACh R
    • Increases Akt R
    • Increases Argininosuccinate R
    • Increases Bax R
    • Increases BzR (high concetrations agonize, low concentrations antagonize) R R
    • Increases Caspase-3 R
    • Increases Caspase-8 R
    • Increases Caspase-9 R
    • Increases cAMP R R
    • Increases GABAR (ionotropic agonist) R
    • Increases GCK R
    • Increases GSH R R
    • Increases HDL-C R
    • Increases IκBα R
    • Increases IL-2 R
    • Increases nm23 R
    • Increases NRF2 R
    • Increases Ornithine R
    • Increases PARP R
    • Increases PEA3 R
    • Increases PAkt R
    • Increases PFK-1 R
    • Increases PI3K R
    • Increases PK R
    • Increases Putrescine R
    • Increases SOD R R
    • Increases Spermidine R
    • Increases STAT-1 R
    • Increases TIMP-2 R
    • Increases 5-HT2R R
    • Increases 5-oxoproline R
    • Reduces α-Amylase R
    • Reduces α-Glucosidase R
    • Reduces AChE R
    • Reduces ALOX15 R
    • Reduces AMPK R
    • Reduces AP-1 R
    • Reduces c-Fos R
    • Reduces c-JNK R
    • Reduces C/EBPα/β R
    • Reduces Cathepsin B R
    • Reduces COX-2 R
    • Reduces CRP R
    • Reduces Cyclin D1 R
    • Reduces Cyclin E R
    • Reduces CYP2C9 R
    • Reduces CYP3A4 R
    • Reduces D3 R
    • Reduces DOR R
    • Reduces ERK R
    • Reduces E-slectin R
    • Reduces ET-1 R
    • Reduces FAS(NR
    • Reduces G-6-Pase R
    • Reduces Glucose R
    • Reduces GM-CSF R
    • Reduces GSK-3 R
    • Reduces HOMA-IR R
    • Reduces Insulin R
    • Reduces IL-1b R R R
    • Reduces IL-6 R R R R
    • Reduces IL-8 R R
    • Reduces IL-17A R 
    • Reduces IL-22 R
    • Reduces IL-23 R
    • Reduces JAK2 R
    • Reduces KOR R
    • Reduces LDL-C R
    • Reduces Lysyl Oxidase R
    • Reduces MDA R R
    • Reduces MMP-1 R
    • Reduces MMP-2 R
    • Reduces MMP-9 R
    • Reduces mTOR R R
    • Reduces NF-κB R
    • Reduces NO (increases in vascular system) R R R R R
    • Reduces PAF R
    • Reduces PEPCK R
    • Reduces PGE-2 R R
    • Reduces PKB R
    • Reduces PPAR-gamma R
    • Reduces Prolyl Hydroxylase R
    • Reduces PTP1B R
    • Reduces ROCK-II R
    • Reduces ROS R R
    • Reduces Skp2 R
    • Reduces SREBP-1 R
    • Reduces TC R
    • Reduces TCTP R
    • Reduces TG R
    • Reduces TLR4 R
    • Reduces TNF-alpha R R R
    • Reduces VCAM-1 R
    • Reduces VEGF R R
    • Reduces 5-HT1DR R
    • Reduces 5-HT2CR R

    Advanced:

    • 3′8"-biapigenin (amentoflavone) is found in over 120 plants as apigenin can be formed into AF through C–C linkages, R
    • Amentoflavone can inhibit FASN expression in human epidermal growth factor receptor 2 (HER2)-positive human breast carcinoma SKBR3 cells. R
    • Amentoflavone, a well known biflavonoid, inhibited the increase of Lamin A or phospho-H2AX protein in dose dependent manner which was induced by UVB irradiation, and also protected nuclear aberration dramatically. R
    • Oral administration of amentoflavone attenuated depression induced by metergoline (5-HT2 receptor antagonist), prazosin (α1-adrenoceptor antagonist), or yohimbine (α2-adrenoceptor antagonist), and to ameliorate anxiety stimulated by flumazenil (ionotropic GABA receptor antagonist). R
    • In the hippocampus, AF may increase SOD, GSH, and glutathione reductase (GR) in response to high concentration of glutamate. R
    • It can also decrease IL-1b, IL-6 and nitric oxide (NO) in the hippocampus. R
    • Amentoflavone could increase the NO content, decrease the levels of VCAM-1, E-selectin, IL-6, IL-8, and ET-1, enhance SOD activity, reduce MDA content, downregulate the protein expressions of VCAM-1, E-selectin, and NF-κB p65, up-regulate IκBα, and attenuate the NF-κB p65 transfer to the cell nucleus, which proved its protection on vascular endothelial cells. R
    • In human keratinocytes, AF Inhibited cell proliferation, promoted apoptosis, decreased overexpression of cyclin D1, cyclin E, IL-17A, IL-22, and inhibited the up-regulation of p65 NF-κB. R
    • In mice colon cells, AF decreased mucosal injury score and vascular permeability, diminished LDH and MPO activity, increased GSH, SOD; decreased LPO, NO, reduced the colonic TNF-α, IL-1β, IL-6, inhibited expression of iNOS and COX-2, and inhibited activation and translocation of NF-κB (p65/p50). R
    • AF can bind to the benzodiazepine receptor (BzR) with a high affinity similar to that of diazepam. R R
    • AF influences a variety of G protein-coupled receptors for serotonin, dopamine, and opioids at nM concentrations, while having no effect on the binding of muscimol, a GABA type A agonist to GABA type A receptors. R
    • For example, AF can significantly inhibited binding at serotonin (5-HT(1D), 5-HT(2C)), D(3)-dopamine, delta-opiate, and benzodiazepine receptors. R
    • Amentoflavone has been shown to be a weak negative allosteric modulator of GABA action. R
    • Amentoflavone had little or no affinity for α4-containing or α6-containing receptors. R
    • AF in hepatic cancer was able to increase the expression of PI3K, Akt, and pAkt and the activity of 6-phosphofructokinas (PFK-1), glucokinase (GCK), and pyruvate kinase (PK), while the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxylase kinase (PEPCK), and glucose-6-phosphatase (G-6-Pase) as well as the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C reactive protein (CRP) decreased. R
    • Amentoflavone can to bind VEGFs preventing the interaction and phosphorylation of VEGF receptor 1 and 2 (VEGFR-1,VEGFR-2) and to inhibit endothelial cell migration and capillary-like tube formation induced by VEGF-A or placental growth factor 1 (PlGF-1) at low μMconcentration. R
    • In vivo, amentoflavone is able to inhibit VEGF-A-induced chorioallantoic membrane neovascularization as well as tumor growth and associated neovascularization. R

    More Research