7,8-DihydroxyflavoneTrkB agonist CAS# 38183-03-8 |
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Quality Control & MSDS
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Chemical structure
3D structure
Cas No. | 38183-03-8 | SDF | Download SDF |
PubChem ID | 1880 | Appearance | Powder |
Formula | C15H10O4 | M.Wt | 254.24 |
Type of Compound | Flavonoids | Storage | Desiccate at -20°C |
Synonyms | 7,8-DHF | ||
Solubility | DMSO : ≥ 100 mg/mL (393.33 mM) *"≥" means soluble, but saturation unknown. | ||
Chemical Name | 7,8-dihydroxy-2-phenylchromen-4-one | ||
SMILES | C1=CC=C(C=C1)C2=CC(=O)C3=C(O2)C(=C(C=C3)O)O | ||
Standard InChIKey | COCYGNDCWFKTMF-UHFFFAOYSA-N | ||
Standard InChI | 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 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | 1. 7,8-Dihydroxyflavone(7,8-DHF) shows anti-inflammatory and anti-oxidant properties, it can be used as a potent facultative ingredient in health-beneficial agents to prevent or treat the skin aging or inflammatory skin disorders. 2. Treatment with 7,8-DHF during the early postnatal period restores the major trisomy-linked neurodevelopmental defects, suggesting that therapy with 7,8-DHF may represent a possible breakthrough for Down syndrome. 3. 7,8-DHF improves mitochondrial respiration in STs from obese women, suggesting that the obese phenotype in the placenta can be rescued by TRKB activation. 4. 7,8-DHF is beneficial for both depression and anxiety-like behaviors, and may exert fast-onset antidepressant effects. 5. 7,8-DHF exhibits anti-melanogenic activity through inhibition of tyrosinase activity in α-MSH-stimulating condition, it also shows anticancer activity in melanoma cells via downregulation of α-MSH/cAMP/MITF pathway. 6. 7,8-DHF ameliorates motor deficits via suppressing α-synuclein expression and oxidative stress in the MPTP-induced mouse model of Parkinson's disease. 7. 7,8-DHF has an anti-obesity effect in vitro, it inhibits adipocyte differentiation via antioxidant activity and induces apoptosis in 3T3-L1 preadipocyte cells. 8. 7,8-DHF has vasorelaxing and antihypertensive effects . |
Targets | TNF-α | MMP(e.g.TIMP) | ROS | HO-1 | p38MAPK | SOD | Akt | cAMP | HIF | PPAR | Calcium Channel |
7,8-Dihydroxyflavone Dilution Calculator
7,8-Dihydroxyflavone Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 3.9333 mL | 19.6665 mL | 39.3329 mL | 78.6658 mL | 98.3323 mL |
5 mM | 0.7867 mL | 3.9333 mL | 7.8666 mL | 15.7332 mL | 19.6665 mL |
10 mM | 0.3933 mL | 1.9666 mL | 3.9333 mL | 7.8666 mL | 9.8332 mL |
50 mM | 0.0787 mL | 0.3933 mL | 0.7867 mL | 1.5733 mL | 1.9666 mL |
100 mM | 0.0393 mL | 0.1967 mL | 0.3933 mL | 0.7867 mL | 0.9833 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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A flavonoid agonist of the TrkB receptor for BDNF improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn mouse model of DS.[Pubmed:28882412]
Exp Neurol. 2017 Dec;298(Pt A):79-96.
Intellectual disability is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Reduced neurogenesis and impaired neuron maturation are considered major determinants of altered brain function in DS. Since the DS brain starts at a disadvantage, attempts to rescue neurogenesis and neuron maturation should take place as soon as possible. The brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain development by specifically binding to tropomyosin-related kinase receptor B (TrkB). Systemic BDNF administration is impracticable because BDNF has a poor blood-brain barrier penetration. Recent screening of a chemical library has identified a flavone derivative, 7,8-Dihydroxyflavone (7,8-DHF), a small-molecule that crosses the blood-brain barrier and binds with high affinity and specificity to the TrkB receptor. The therapeutic potential of TrkB agonists for neurogenesis improvement in DS has never been examined. The goal of our study was to establish whether it is possible to restore brain development in the Ts65Dn mouse model of DS by targeting the TrkB receptor with 7,8-DHF. Ts65Dn mice subcutaneously injected with 7,8-DHF in the neonatal period P3-P15 exhibited a large increase in the number of neural precursor cells in the dentate gyrus and restoration of granule cell number, density of dendritic spines and levels of the presynaptic protein synaptophysin. In order to establish the functional outcome of treatment, mice were treated with 7,8-DHF from P3 to adolescence (P45-50) and were tested with the Morris Water Maze. Treated Ts65Dn mice exhibited improvement of learning and memory, indicating that the recovery of the hippocampal anatomy translated into a functional rescue. Our study in a mouse model of DS provides novel evidence that treatment with 7,8-DHF during the early postnatal period restores the major trisomy-linked neurodevelopmental defects, suggesting that therapy with 7,8-DHF may represent a possible breakthrough for Down syndrome.
7,8-Dihydroxyflavone attenuates TNF-alpha-induced skin aging in Hs68 human dermal fibroblast cells via down-regulation of the MAPKs/Akt signaling pathways.[Pubmed:28950658]
Biomed Pharmacother. 2017 Nov;95:1580-1587.
7,8-Dihydroxyflavone (7,8-DHF, 7,8-dihydroxy-2-phenyl-4H-chromen-4-one) is a natural flavone found in plants and has been frequently reported to show anti-inflammatory and anti-oxidant properties. Skin aging is induced mainly by oxidative stress. In the present study, we evaluated 7,8-DHF for its potential anti-aging effects for skin using Hs68 human dermal fibroblast cells. To establish aged skin cell model, Hs68 cells were treated with tumor necrosis factor-alpha (TNF-alpha) for 18h 7,8-DHF (0-10muM) induced collagen synthesis and suppressed the expression of matrix metalloproteinase 1 (MMP 1) in a dose-dependent manner. 7,8-DHF also significantly reduced the generation of intracellular reactive oxygen species (ROS), induced the expression of anti-oxidant enzymes, such as catalase, manganese superoxide dismutase (Mn-SOD), and heme oxygenase-1 (HO-1), and scavenged DPPH free radicals. 7,8-DHF also disturbed the mitogen-activated protein kinases (MAPKs) and Akt signaling pathways that participate in the aging process. 7,8-DHF exerted potent anti-aging effects by inhibiting MMP 1 expression and inducing Type I collagen synthesis in Hs68 cells. 7,8-DHF effectively attenuated oxidative stress by up-regulating the anti-oxidant enzymes catalase, Mn-SOD, and HO-1, and reducing activation of the Akt and MAPKs signaling pathways in aged skin cells. These results suggest that 7,8-DHF can be used as a potent facultative ingredient in health-beneficial agents to prevent or treat the skin aging or inflammatory skin disorders.
Anticancer activity of 7,8-dihydroxyflavone in melanoma cells via downregulation of alpha-MSH/cAMP/MITF pathway.[Pubmed:27220989]
Oncol Rep. 2016 Jul;36(1):528-34.
Malignant melanoma is one of the most aggressive skin cancer and highly resistant to most conventional treatment. In the present study, we aimed to investigate the anticancer effects and mechanisms of action of 7,8-Dihydroxyflavone (7,8-DHF), a monophenolic flavone, in melanoma cells. At concentrations not exhibiting cytotoxicity, 7,8-DHF potently inhibited growth and clonogenic survival of alpha-melanocyte stimulating hormone (alpha-MSH)-stimulated B16F10 melanoma cells. Furthermore, it significantly blocked migration and invasion of the metastatic melanoma cells. We also observed that 7,8-DHF exhibits anti-melanogenic activity through inhibition of tyrosinase activity in alpha-MSH-stimulating condition. Notably, the suppressive activities of 7,8-DHF on melanoma progression were associated with the downregulation of microphthalmia-associated transcription factor (MITF) and its main downstream transcription targets, including hypoxia-inducible factor 1alpha (HIF1alpha) and c-MET, by a decrease in cyclic adenosine monophosphate (cAMP) level. In addition, combination treatment with 7,8-DHF and resveratrol, a known therapeutic agent against melanoma, had greater anticancer activities and MITF inhibition than treatment with each single agent in alpha-MSH-treated B16F10 cells. Collectively, these findings may contribute to the potential application of 7,8-DHF in the prevention and treatment of malignant melanoma.
7,8-Dihydroxyflavone, a Tropomyosin-Kinase Related Receptor B Agonist, Produces Fast-Onset Antidepressant-Like Effects in Rats Exposed to Chronic Mild Stress.[Pubmed:27757132]
Psychiatry Investig. 2016 Sep;13(5):531-540.
OBJECTIVE: Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), play important roles in treating depression. In this experiment, we examined whether 7,8-Dihydroxyflavone, a novel potent TrkB agonist, could reverse the behavioral and biochemical abnormalities induced by the chronic mild stress (CMS) paradigm in rats. METHODS: SD rats were exposed to a battery of stressors for 56 days. 7,8-Dihydroxyflavone (5 and 20 mg/kg) were administered intraperitoneally during the last 28 days of the CMS paradigm. Rats were tested in sucrose consumption test (SCT), forced-swimming test (FST) and elevated T-maze (ETM). Serum corticosterone levels and hippocampal BDNF levels of the rats were measured. RESULTS: Four-week CMS on the rats induced their depression-like behavior in SCT. The CMS-reduced sucrose consumption was reversed starting from 7 days after the 7,8-Dihydroxyflavone (20 mg/kg) treatment and remained across the subsequent treatment regime. 7,8-Dihydroxyflavone, when given at 5 mg/kg for 3 weeks, reduced the immobility time in the FST in the CMS-subjected rats. Additionally, the 4-week treatment with 7,8-Dihydroxyflavone (20 mg/kg) attenuated the CMS-induced increase in anxiety-like behavior in the ETM. For the CMS-subjected rats, 7,8-Dihydroxyflavone treatment dose-dependently reduced their serum corticosterone levels but increased their hippocampal BDNF levels only at 5 mg/kg. CONCLUSION: 7,8-Dihydroxyflavone was beneficial for both depression and anxiety-like behaviors, and may exert fast-onset antidepressant effects. This provides a new insight into the pharmacological management of depression.
Vasorelaxing and antihypertensive effects of 7,8-dihydroxyflavone.[Pubmed:24317273]
Am J Hypertens. 2014 May;27(5):750-60.
BACKGROUND: Although 7,8-Dihydroxyflavone (7,8-DHF) has been demonstrated to be potently neuroprotective, its effect on vascular function remains unknown. METHODS: The effect of 7,8-DHF on phenylephrine (PE)-induced preconstriction was examined with aortic rings isolated from normal rats. Its effective mechanisms were studied with blockers, Western blotting, and primarily cultured vascular smooth myocytes. The blood pressure (BP) of rats was measured with a tail cuff method. RESULTS: 7,8-DHF dose-dependently dilated the PE-preconstricted, endothelia-intact aortic rings with concentration for 50% of maximal effect (EC50) of approximately 24 microM. Both Nomega-nitro-L-arginine methyl ester hydrochloride, a nitric oxide synthase inhibitor, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a soluble guanylyl cyclase blocker, significantly reduced the vasorelaxing effect of 7,8-DHF. Western blotting showed that 7,8-DHF increased the aortic endothelial nitric oxide synthase protein expression and phosphorylation. With endothelia removed, 7,8-DHF also dilated the PE-preconstricted rings but with EC50 of approximately 104 microM. Ca(2+) imaging experiments detected that 7,8-DHF probably blocked both intracellular Ca(2+) release and extracellular Ca(2+) influx. Therefore, the mechanisms of 7,8-DHF dilating effect might be stimulating the nitric oxide/cGMP production and blocking the Ca(2+) signaling pathway instead of tropomyosin receptor kinase B receptors because ANA-12, its specific antagonist, did not show any effect against 7,8-DHF. When administered intravenously, 7,8-DHF significantly reduced the BP of the spontaneously hypertensive rats. However, when used orally, there was only a slight but significant reduction in the diastolic pressure. CONCLUSIONS: The results suggest that neuro-protective 7,8-DHF is also a vasorelaxing and antihypertensive substance in rats.
7,8-Dihydroxyflavone inhibits adipocyte differentiation via antioxidant activity and induces apoptosis in 3T3-L1 preadipocyte cells.[Pubmed:26631505]
Life Sci. 2016 Jan 1;144:103-12.
AIMS: Anti-obesity effects of a natural plant flavonoid 7,8-Dihydroxyflavone (7,8-DHF) were evaluated using 3T3-L1 preadipocyte cells. MAIN METHODS: The cell viability was determined using MTT assay. Effects of 7,8-DHF on intracellular lipid droplets and intracellular reactive oxygen species (ROS) were measured using a 2,7-dichlorofluorescein diacetate (DCF-DA) assay and Oil Red O staining method, respectively. Apoptotic cell death was monitored by annexin V-FITC/PI double staining and by a TUNEL assay. Antioxidant enzyme mRNA levels and protein expression of adipogenic transcription factors were determined by real-time PCR and Western blotting, respectively. KEY FINDINGS: Whereas the cell viability of 3T3-L1 preadipocytes was not affected by lower concentrations of 7,8-DHF (<20 muM), higher concentrations of 7,8-DHF (>20 muM) induced apoptotic cell death. 7,8-DHF (<20 muM) significantly reduced the intracellular lipid droplets and the expression of major adipogenic transcription factors, such as CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), C/EBP-beta, and peroxisome proliferator activated receptor-gamma (PPAR-gamma). 7,8-DHF treatment also dose-dependently reduced the intracellular ROS level, attenuated MAPK pathway activation, and increased the expression of antioxidant enzymes, such as Mn-superoxide dismutase (Mn-SOD), catalase (CAT), and heme oxygenase-1 (HO-1). SIGNIFICANCE: The results of this study indicated that 7,8-DHF inhibits the adipogenesis of 3T3-L1 preadipocyte cells by down-regulating the expression of adipogenic transcription factors, reduces lipid accumulation, and attenuates ROS accumulation by inducing antioxidant enzymes in differentiated 3T3-L1 cells, suggesting for the first time that 7,8-DHF has an anti-obesity effect in vitro via its anti-oxidant activity.
7,8-dihydroxyflavone Ameliorates Motor Deficits Via Suppressing alpha-synuclein Expression and Oxidative Stress in the MPTP-induced Mouse Model of Parkinson's Disease.[Pubmed:27079181]
CNS Neurosci Ther. 2016 Jul;22(7):617-24.
BACKGROUND: Parkinson disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and diminished dopamine content in the striatum, which is at least partly associated with alpha-synuclein protein overexpression in these neurons. Recent reports show that 7,8-Dihydroxyflavone (DHF), a TrkB agonist, has beneficial effects in animal model of PD. However, it is unclear whether the therapeutic effects of DHF are associated with the expression of alpha-synuclein. AIMS: In this study, we investigated the protective effects of DHF on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced deficit of motor functions, the loss of dopaminergic neurons and the expression of alpha-synuclein as well as antioxidative activity in the C57BL/6 mice. RESULTS: Mice were treated with MPTP (30 mg/kg, i.p.) once a day for 5 days to induce dopaminergic neuron death in the SN. DHF (5 mg/kg, i.p.) was administrated once a day from the first day of MPTP injection until 9 days after the last injection of MPTP. Behavioral tests showed that DHF succeeded in ameliorating the impaired motor functions in the MPTP-treated mice. The immunohistochemical assay showed that the amelioration of motor function was accompanied by a reduction in the loss of dopaminergic neurons in the SN and striatum. Western blot analyses showed that DHF prevented the inactivation of TrkB and suppressed alpha-synuclein overexpression in the SN and striatum following MPTP treatment. Antioxidative activity detection revealed that DHF prevented MPTP-induced reduction in glutathione and total superoxide dismutase activity in the SN and striatum. CONCLUSION: Taken together, these results indicate that DHF treatment may suppress the accumulation of alpha-synuclein and oxidative stress via activating TrkB and subsequently block the loss of dopaminergic neurons in the SN and striatum, thereby ameliorating MPTP-induced motor deficits in the C57BL/6 mice.
Tropomyosin Receptor Kinase B Agonist, 7,8-Dihydroxyflavone, Improves Mitochondrial Respiration in Placentas From Obese Women.[Pubmed:28677406]
Reprod Sci. 2018 Mar;25(3):452-462.
Maternal obesity negatively impacts the placenta, being associated with increased inflammation, decreased mitochondrial respiration, decreased expression of brain-derived neurotrophic factor (BDNF), and its receptor, tropomyosin receptor kinase B (TRKB). TRKB induction by 7,8-Dihydroxyflavone (7,8-DHF) improves energy expenditure in an obesity animal model. We hypothesized that TRKB activation would improve mitochondrial respiration in trophoblasts from placentas of obese women. Placentas were collected from lean (pre-pregnancy BMI < 25) and obese (pre-pregnancy BMI > 30) women at term following cesarean section delivery without labor. Cytotrophoblasts were isolated and plated, permitting syncytialization. At 72 hours, syncytiotrophoblasts (STs) were treated for 1 hour with 7,8-DHF (10 nM-10 M), TRKB antagonists (ANA-12 (10 nM-1 M), Cyclotraxin B (1 nM-1M)), or vehicle. Mitochondrial respiration was measured using the XF24 Extracellular Flux Analyzer. TRKB, MAPK, and PGC1alpha were measured using Western blotting. Maternal obesity was associated with decreased mitochondrial respiration in STs; however, 7,8-DHF increased basal, ATP-coupled, maximal, spare capacity, and nonmitochondrial respiration. A 10 muM dose of 7,8-DHF reduced spare capacity in STs from lean women, with no effect on other respiration parameters. 7,8-DHF had no effect on TRKB phosphorylation; however, there was a concentration-dependent decrease of p38 MAPK phosphorylation and increase of PGC1alpha in STs from obese, but not in lean women. TRKB antagonism attenuated ATP-coupled respiration, maximal respiration, and spare capacity in STs from lean and obese women. 7,8-DHF improves mitochondrial respiration in STs from obese women, suggesting that the obese phenotype in the placenta can be rescued by TRKB activation.
Small-molecule TrkB receptor agonists improve motor function and extend survival in a mouse model of Huntington's disease.[Pubmed:23446639]
Hum Mol Genet. 2013 Jun 15;22(12):2462-70.
Huntington's disease (HD) is a fatal neurodegenerative disease characterized by abnormal motor coordination, cognitive decline and psychiatric disorders. This disease is caused by an expanded CAG trinucleotide repeat in the gene encoding the protein huntingtin. Reduced levels of brain-derived neurotrophic factor (BDNF) in the brain, which results from transcriptional inhibition and axonal transport deficits mediated by mutant huntingtin, have been suggested as critical factors underlying selective neurodegeneration in both HD patients and HD mouse models. BDNF activates its high-affinity receptor TrkB and promotes neuronal survival; restoring BDNF signaling is thus of particular therapeutic interest. In the present study, we evaluated the ability of a small-molecule TrkB agonist 7,8-Dihydroxyflavone (7,8-DHF) and its synthetic derivative 4'-dimethylamino-7,8- dihydroxyflavone (4'-DMA-7,8-DHF) to protect neurons in the well-characterized N171-82Q HD mouse model. We found that chronic administration of 7, 8-DHF (5 mg/kg) or 4'-DMA-7,8-DHF (1 mg/kg) significantly improved motor deficits, ameliorated brain atrophy and extended survival in these N171-82Q HD mice. Moreover, 4'-DMA-7,8-DHF preserved DARPP32 levels in the striatum and rescued mutant huntingtin-induced impairment of neurogenesis in the N171-82Q HD mice. These data highlight consideration of TrkB as a therapeutic target in HD and suggest that small-molecule TrkB agonists that penetrate the brain have high potential to be further tested in clinical trials of HD.
7,8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats.[Pubmed:21136519]
Hippocampus. 2012 Mar;22(3):399-408.
Post-traumatic stress disorder (PTSD) patients show cognitive deficits, but it is unclear whether these are a consequence of the pathology or a pre-existing factor of vulnerability to PTSD. Animal models may help to demonstrate whether or not exposure to certain stressors can actually induce long-lasting (LL; days) impairment of hippocampus-dependent memory tasks and to characterize neurobiological mechanisms. Adult male rats were exposed to 2-h immobilization on boards (IMO), a severe stressor, and spatial learning in the Morris water maze (MWM) was studied days later. Exposure to IMO did not modify learning or short-term memory in the MWM when learning started 3 or 9 days after IMO, but stressed rats did show impaired long-term memory at both times, in accordance with the severity of the stressor. New treatments to prevent PTSD symptoms are needed. Thus, considering the potential protective role of brain-derived neurotrophic factor (BDNF) on hippocampal function, 7,8-Dihydroxyflavone (7,8-DHF), a recently characterized agonist of the BDNF receptor TrkB, was given before or after IMO in additional experiments. Again, exposure to IMO resulted in LL deficit in long-term memory, and such impairment was prevented by the administration of 7,8-DHF either 2 h prior IMO or 8 h after the termination of IMO. The finding that IMO-induced impairment of spatial memory was prevented by pharmacological potentiation of TrkB pathway with 7,8-DHF even when the drug was given 8 h after IMO suggests that IMO-induced impairment is likely to be a LL process that is strongly dependent on the integrity of the BDNF-TrkB system and is susceptible to poststress therapeutic interventions. 7,8-DHF may represent a new therapeutic approach for early treatment of subjects who have suffered traumatic experiences.