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Amentoflavone

Alias: Didemethylginkgetin; Amentoflavone; 1617-53-4; Didemethyl-ginkgetin; 3',8''-Biapigenin; Amenthoflavone; I3,II8-biapigenin; Tridemethylsciadopitysin; MFCD00017470;
Cat No.:V7371 Purity: ≥98%
Amentoflavone (Didemethyl-ginkgetin) is a potent and orally bioactive negative modulator of GABA(A).
Amentoflavone
Amentoflavone Chemical Structure CAS No.: 1617-53-4
Product category: GABA Receptor
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
Amentoflavone (Didemethyl-ginkgetin) is a potent and orally bioactive negative modulator of GABA(A). Amentoflavone also displays anti~inflammatory, antioxidant, antiviral, antitumor, antiradiation, and anti-bacterial effect. Amentoflavone causes apoptosis and cell cycle arrest in the sub-G1 phase.
Biological Activity I Assay Protocols (From Reference)
Targets
Natural biflavonoid; antioxidative; anti-inflammatory; anti-viral; anti-tumor
ln Vitro
In RAW 264.7 cells, amenoflavone (1-60 μM) suppresses the generation of nitric oxide in a concentration-dependent way [2]. U-87 MG cell viability is inhibited by amentoflavone (50-200 μM) with an IC50 value of 100 μM after 48 hours [3]. In the sub-G1 phase, amentoflavone (0, 50, and 100 μM; 48 hours) causes cell cycle arrest and apoptosis [3]. In U-87 MG cells, amentoflavone (0, 50, 100 μM; 48 h) suppresses NF-κB activation and lowers MCL1 and C-FLIP protein expression [3]. With minimum inhibitory concentrations (MICs) of 8, 4, 32, 8, 16, and 8 μg/ml, amentoflavone (0-32 μg/ml) exhibits antibacterial action against Enterococcus faecium ATCC 19434, Staphylococcus aureus ATCC 25923, Streptococcus mutans ATCC 3065, and Escherichia coli. ml. They're E. O. 157 ATCC 25922, E. coli. Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 43895 [4].
ln Vivo
Through its anti-inflammatory properties in mice, amentoflavone (25 mg/kg; oral; once daily for 3 days) has been demonstrated to be neuroprotective in epilepsy [1].
Cell Assay
Cell viability assay [3]
Cell Types: U-87 MG Cell
Tested Concentrations: 0, 50, 75, 100, 200 µM
Incubation Duration: 48 hrs (hours)
Experimental Results: Dramatically inhibited the viability of U-87 MG cells by 23-71% at 48 hrs (hours) The IC50 value is 100 µM.

Apoptosis analysis [3]
Cell Types: U-87 MG Cell
Tested Concentrations: 0, 50, 100 µM
Incubation Duration: 48 hrs (hours)
Experimental Results: Dramatically induced the accumulation of cells in the sub-G1 population and increased the levels of active caspase-3 respectively 14-52% and 24-42%, and Dramatically induced Ψm loss and active caspase-8 expression by 23-53% and 25-50%, respectively.

Western Blot Analysis[3]
Cell Types: U-87 MG Cell
Tested Concentrations: 0, 50, 100 µM
Incubation Duration: 48 hrs (hours)
Experimental Results: Dramatically diminished NF-ĸB activation by 25-87% in a dose-dependent manner and diminished protein expression MCL1 and C-FLIP increased by 50-80% and 38-57% respectively.
Animal Protocol
Animal/Disease Models: 5-6 weeks, 28-32 g, Kunming mice [1]
Doses: 25 mg/kg
Route of Administration: Po; one time/day for 3 days
Experimental Results: Inhibition of the activation and nuclear activation of NF-κB subunit p65 translocation, reducing the production of IL-6 and IL-1β, and Dramatically reducing the production of NO and prostaglandin E2.
References

[1]. Amentoflavone protects hippocampal neurons: anti-inflammatory, antioxidative, and antiapoptotic effects. Neural Regen Res. 2015 Jul;10(7):1125-33.

[2]. Amentoflavone inhibits the induction of nitric oxide synthase by inhibiting NF-kappaB activation in macrophages. Pharmacol Res. 2005 Jun;51(6):539-46.

[3]. Amentoflavone Induces Apoptosis and Inhibits NF-ĸB-modulated Anti-apoptotic Signaling in Glioblastoma Cells. In Vivo. 2018 Mar-Apr;32(2):279-285.

[4]. Antibacterial effect of amentoflavone and its synergistic effect with antibiotics. J Microbiol Biotechnol. 2013;23(7):953-8.

[5]. Semisynthetic preparation of amentoflavone: A negative modulator at GABA(A) receptors. Bioorg Med Chem Lett. 2003 Jul 21;13(14):2281-4.

Additional Infomation
Amentoflavone is a biflavonoid that is obtained by oxidative coupling of two molecules of apigenin resulting in a bond between positions C-3 of the hydroxyphenyl ring and C-8 of the chromene ring. A natural product found particularly in Ginkgo biloba and Hypericum perforatum. It has a role as a cathepsin B inhibitor, an antiviral agent, an angiogenesis inhibitor, a P450 inhibitor and a plant metabolite. It is a biflavonoid, a hydroxyflavone and a ring assembly.
Amentoflavone has been reported in Cycas beddomei, Microbiota decussata, and other organisms with data available.
See also: ... View More ...
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C30H18O10
Molecular Weight
538.46
Exact Mass
538.09
Elemental Analysis
C, 66.92; H, 3.37; O, 29.71
CAS #
1617-53-4
Related CAS #
1617-53-4 38Biapigenin
PubChem CID
5281600
Appearance
Light yellow to yellow solid powder
Density
1.7±0.1 g/cm3
Boiling Point
910.5±65.0 °C at 760 mmHg
Melting Point
>300ºC
Flash Point
308.5±27.8 °C
Vapour Pressure
0.0±0.3 mmHg at 25°C
Index of Refraction
1.793
LogP
3.11
Hydrogen Bond Donor Count
6
Hydrogen Bond Acceptor Count
10
Rotatable Bond Count
3
Heavy Atom Count
40
Complexity
1050
Defined Atom Stereocenter Count
0
InChi Key
YUSWMAULDXZHPY-UHFFFAOYSA-N
InChi Code
InChI=1S/C30H18O10/c31-15-4-1-13(2-5-15)24-12-23(38)29-21(36)10-20(35)27(30(29)40-24)17-7-14(3-6-18(17)33)25-11-22(37)28-19(34)8-16(32)9-26(28)39-25/h1-12,31-36H
Chemical Name
8-[5-(5,7-dihydroxy-4-oxochromen-2-yl)-2-hydroxyphenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
Synonyms
Didemethylginkgetin; Amentoflavone; 1617-53-4; Didemethyl-ginkgetin; 3',8''-Biapigenin; Amenthoflavone; I3,II8-biapigenin; Tridemethylsciadopitysin; MFCD00017470;
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : ~125 mg/mL (~232.14 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.64 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 (4.64 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
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.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.8571 mL 9.2857 mL 18.5715 mL
5 mM 0.3714 mL 1.8571 mL 3.7143 mL
10 mM 0.1857 mL 0.9286 mL 1.8571 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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.
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Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04373421 COMPLETEDWITH RESULTS Drug: Chlorhexidine Gluconate 0.12 % Mouthwash +
benzydamine hydrochloride
Procedure: St. John's wort oil
Procedure: Virgin olive oil
Impacted Third Molar Tooth Yuzuncu Yıl University 2018-08-15 Phase 4
Biological Data
  • Effects of amentoflavone on NF-κB p65 protein expression in the hippocampus of mice with status epilepticus (western blot assay). Quantitative results are expressed as gray value ratio (NF-κB p65/β-tubulin) in all groups. Comparison of the intensity ratio shows significantly decreased NF-κB p65 protein expression in the hippocampus of epileptic mice compared to the AP group (*P < 0.05, **P < 0.01). Data are expressed as the mean ± SEM (n = 10) and were analyzed using one-way analysis of variance and Dunnett's post-hoc test. AP: Amentoflavone pre-treated group; AT: amentoflavone-treated group; VPA: valproate-treated group; EP: non-treated-epilepsy group; Blank: blank control group; NF: nuclear factor.[1].Zhang Z, et al. Amentoflavone protects hippocampal neurons: anti-inflammatory, antioxidative, and antiapoptotic effects. Neural Regen Res. 2015 Jul;10(7):1125-33.
  • Amentoflavone effects on neuronal injury in the hippocampal CA1 of mice with status epilepticus (Nissl staining). (A) Nissl staining was used to identify Nissl bodies and the extent of neuronal damage in the CA1 subfield (×400). (A1–A5) AP, AT, VPA, EP, and blank groups, respectively. (A2–A4) Hippocampal CA1 neurons were loose and absent; the cytoplasm was stained in different shades; nucleoli were missing or indistinct (arrows). (A1, A5) Neurons were neatly arranged and displayed sharp edges. Nissl bodies showed visible cytoplasm. (B) Neuronal counts. In the amentoflavone-treated group, neurons were fairly well preserved and sparse in the CA1 subregion. *P < 0.05, **P < 0.01. Data are expressed as the mean ± SEM (n = 10) and analyzed using one-way analysis of variance and Dunnett's post-hoc test. AP: Amentoflavone pre-treated group; AT: amentoflavone-treated group; VPA: valproate-treated group; EP: non-treated-epilepsy group; Blank: blank control group.[1].Zhang Z, et al. Amentoflavone protects hippocampal neurons: anti-inflammatory, antioxidative, and antiapoptotic effects. Neural Regen Res. 2015 Jul;10(7):1125-33.
  • Amentoflavone effects on cell apoptosis in the hippocampal CA1 of mice with status epilepticus (TUNEL staining). (A) TUNEL staining was used to observe differences in apoptosis (×400). (A1–A5) AP, AT, VPA, EP, and blank groups. TUNEL-positive cells were quantified at 400× magnification. (A1) Sparse TUNEL-positive cells in CA1 subfield; (A1, A5) scarce TUNEL-positive cells; (A2–A4) significantly increased number of TUNEL-positive cells (arrows). (B) TUNEL-positive cell counts. No significant difference was observed between the blank and AP groups. *P < 0.05, **P < 0.01. Data are expressed as the mean ± SEM (n = 10) and analyzed using one-way analysis of variance and Dunnett's post-hoc test. AP: Amentoflavone pre-treated group; AT: amentoflavone-treated group; VPA: valproate-treated group; EP: non-treated-epilepsy group; Blank: blank control group; TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling.[1].Zhang Z, et al. Amentoflavone protects hippocampal neurons: anti-inflammatory, antioxidative, and antiapoptotic effects. Neural Regen Res. 2015 Jul;10(7):1125-33.
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