| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
TrkB (Tropomyosin-receptor-kinase B) [1]
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| ln Vitro |
7,8-Dihydroxyflavone (500 nM) protects primary cortical neurons and locus coeruleus (LC) neuron shells from Aβ-induced toxicity and stimulates dendritic development and synapse formation [1].
At 500 nM, 7,8-Dihydroxyflavone protected primary rat cortical neurons from pre-aggregated Aβ(1-42) (20 μM) induced toxicity, significantly reducing the apoptotic rate. This protective effect was blocked by pre-treatment with the Trk receptor inhibitor K252a (100 nM). [1] At 500 nM, 7,8-Dihydroxyflavone protected primary rat locus coeruleus (LC) neurons from pre-aggregated Aβ(25-35) (20 μM) induced apoptosis. This effect was also abolished by K252a (100 nM). [1] At 500 nM for 3 days, 7,8-Dihydroxyflavone significantly increased total dendritic length and promoted dendritic branching (increased number of crossings and area under the curve) in primary cultured rat cortical neurons (DIV 3). [1] At 500 nM for 3 days, 7,8-Dihydroxyflavone increased the number and size of presynaptic structures (co-stained with VGAT and bassoon) in primary cultured neurons. [1] |
| ln Vivo |
In Alzheimer's disease models, 7,8-Dihydroxyflavone (5 mg/kg/day) protects synapse loss and memory deficits [1]. Application of 7,8-dihydroxyflavone to the model has neuroprotective benefits in animal models of Parkinson's disease and activates TrkB in the brain center, suppresses toxicity generated by red algae toxin, and lowers infarct volume in stroke in a TrkB-dependent way [2].
Chronic oral administration (approx. 5 mg/kg/day via drinking water for 4 months, starting at 2 months of age) of 7,8-Dihydroxyflavone to 5XFAD mice significantly elevated levels of phosphorylated TrkB (p-TrkB) in the dentate gyrus, as shown by immunohistochemistry and immunoblotting, without changing total TrkB levels. It also increased phosphorylation of downstream signaling proteins AKT and ERK/MAPK. [1] In 5XFAD mice, the same chronic oral treatment reversed the decreased density of dendritic spines (Golgi stain) and synaptic density (electron microscopy) in the hippocampal CA1 area. It also reversed the decrease in synaptic markers (synaptotagmin, synapsin I, PSD95, spinophilin) measured by immunoblotting. [1] Chronic oral treatment with 7,8-Dihydroxyflavone rescued the impaired long-term potentiation (LTP) at the Schaffer collateral-CA1 pathways in hippocampal slices from 5-month-old 5XFAD mice. It did not affect paired-pulse facilitation (PPF) or the impaired basal synaptic transmission (input/output curves) in these mice. [1] Chronic oral administration of 7,8-Dihydroxyflavone significantly decreased the number of hippocampal plaques (Thioflavin-S staining) and Aβ deposition (immunohistochemistry) in 6-month-old 5XFAD mice, but did not change the total concentration of Aβ42 (ELISA). [1] Chronic oral treatment with 7,8-Dihydroxyflavone rescued spatial memory deficits in 6-month-old 5XFAD mice in the Morris water maze test, improving both acquisition (reduced latency) and memory recall (increased time in target quadrant). [1] |
| Cell Assay |
Primary rat cortical neurons (DIV 12) were exposed to pre-aggregated Aβ(1-42) (20 μM) for 18 hours in the presence or absence of 7,8-Dihydroxyflavone (500 nM). To assess TrkB-dependence, some neurons were pre-treated with the Trk receptor inhibitor K252a (100 nM) for 30 minutes before adding 7,8-DHF. Neuronal apoptosis was detected by TUNEL staining, and neurons were identified by co-immunostaining with the neuronal marker MAP2. The apoptotic index was the percentage of TUNEL-positive neurons out of total MAP2-positive neurons. [1]
Primary rat LC neurons were exposed to pre-aggregated Aβ(25-35) (20 μM) for 18 hours with or without 7,8-Dihydroxyflavone (500 nM) and K252a (100 nM). Cells were stained with tyrosine hydroxylase (TH, red), DAPI (blue), and TUNEL (green) to determine the percentage of apoptotic cells. [1] To measure dendrite elongation, primary rat cortical neurons (DIV 3) were exposed to 7,8-Dihydroxyflavone (500 nM) or vehicle for 3 days. Neurons were then fixed, permeabilized, and immunostained with anti-MAP2 antibody. Images were taken by fluorescence microscopy, and dendritic length and complexity (number of crossings, area under the curve) were scored using ImageJ software. [1] For synaptogenesis assessment, vehicle- or 7,8-Dihydroxyflavone-treated (500 nM, 3 days) primary neurons were double-stained with presynaptic markers VGAT (green) and bassoon (red). The number and size of synapses (presynaptic structures) were analyzed using confocal microscopy and ImageJ software. [1] |
| Animal Protocol |
7,8-Dihydroxyflavone was dissolved in drinking water by adding 1M NaOH dropwise and stirring at room temperature overnight to a final concentration of 22 mg/L (pH 7.6-7.8). Vehicle control was water at pH 7.6-7.8. The estimated daily dose was ~5 mg/kg/day based on a water intake of ~7 ml/30g body weight for C57BL/6J mice. Treatment started at 2 months of age and continued for 4 months until mice were 6 months old. [1]
For electrophysiological analysis, vehicle- and 7,8-Dihydroxyflavone-treated 5XFAD mice (5 months old) were anesthetized with isoflurane and decapitated. Hippocampi were cut into 400-μm thick transverse slices. After incubation, slices were placed in a recording chamber, and fEPSPs were recorded in CA1 stratum radiatum. LTP was induced by 3 theta-burst stimulations (TBS: 4 pulses at 100 Hz, repeated 3 times with a 200-ms interval). PPF was examined with paired pulses separated by 20-500 ms intervals. Input-output curves were constructed by measuring fEPSP slope in response to increasing stimulus intensity (1 to 7V, 0.5V increment). [1] For the Morris water maze test, female wild-type and 5XFAD mice (6 months old) on standard drinking water or 7,8-Dihydroxyflavone were trained for 5 consecutive days (4 trials/day, 15-min intertrial interval) to find an invisible escape platform in a water-filled tub. Maximum trial length was 60s. On day 6, a probe trial was performed with the platform removed, and the percentage of time spent in the target quadrant was measured over 60s. Latency, swim path length, and swim speed were analyzed. [1] |
| ADME/Pharmacokinetics |
The oral bioavailability of 7,8-Dihydroxyflavone is about 5%. [1]
After oral gavage of 50 mg/kg, the half-life (t1/2) of 7,8-Dihydroxyflavone in plasma is about 134 minutes. [1] 7,8-Dihydroxyflavone can penetrate the blood-brain barrier. [1] |
| References | |
| Additional Infomation |
7,8-Dihydroxyflavonoids are flavonoids with hydroxyl groups substituted at the 7 and 8 positions. They are naturally occurring flavonoids produced by a variety of plants, including the weed daisy (Tridax procumbens, also known as coal clump grass or weed daisy) and the horse chestnut (Godmania aesculifolia). In animal models, they have shown therapeutic effects on various neurological disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. They possess multiple functions, including as a plant metabolite, a tropomyosin-associated kinase B receptor agonist, an antidepressant, an antioxidant, and an antitumor drug.
7,8-Dihydroxyflavone is a selective small-molecule TrkB agonist that mimics the physiological actions of BDNF (Brain-derived neurotrophic factor). [1] The study proposes that the therapeutic effect of 7,8-Dihydroxyflavone in the 5XFAD mouse model of Alzheimer's disease is largely attributed to its "synaptoprotective" effect, preventing synaptic loss and dysfunction. [1] Unlike the study by Devi and Ohno (2012) which used intraperitoneal (i.p.) injection in older mice (12-15 months old), the present study used chronic oral administration starting at 2 months of age. This may explain the discrepancy in effects on total Aβ42 concentration and BACE1 expression, as the current study found no change in total Aβ42. [1] |
| Molecular Formula |
C15H10O4
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|---|---|
| Molecular Weight |
254.2375
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| Exact Mass |
254.057
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| CAS # |
38183-03-8
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| PubChem CID |
1880
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
494.4±45.0 °C at 760 mmHg
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| Melting Point |
243-246°C
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| Flash Point |
193.5±22.2 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.699
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| LogP |
2.51
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
19
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| Complexity |
384
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(=C([H])C(C2C([H])=C([H])C(=C(C1=2)O[H])O[H])=O)C1C([H])=C([H])C([H])=C([H])C=1[H]
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| InChi Key |
COCYGNDCWFKTMF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H10O4/c16-11-7-6-10-12(17)8-13(19-15(10)14(11)18)9-4-2-1-3-5-9/h1-8,16,18H
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| Chemical Name |
7,8-Dihydroxy-2-phenyl-chromen-4-one
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| Synonyms |
DHF 7,8-DHF 7,8-Dihydroxyflavone
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~393.33 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9333 mL | 19.6665 mL | 39.3329 mL | |
| 5 mM | 0.7867 mL | 3.9333 mL | 7.8666 mL | |
| 10 mM | 0.3933 mL | 1.9666 mL | 3.9333 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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