12 Benefits of 7,8-Dihydroxyflavone (7,8-DHF) + Side Effects

Intake of 7,8-Dihydroxyflavone During Juvenile and Adolescent Stages Prevents Onset of Psychosis in Adult Offspring After Maternal Immune Activation

12 Benefits of 7,8-Dihydroxyflavone (7,8-DHF) + Side Effects

Prenatal infection and subsequent abnormal neurodevelopment of offspring is involved in the etiology of schizophrenia. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB) signaling plays a key role in the neurodevelopment.

Pregnant mice exposed to polyriboinosinic-polyribocytidylic acid [poly(I:C)] causes schizophrenia- behavioral abnormalities in their offspring at adulthood. Here we found that the juvenile offspring of poly(I:C)-treated mice showed cognitive deficits, as well as reduced BDNF-TrkB signaling in the prefrontal cortex (PFC).

Furthermore, the adult offspring of poly(I:C)-treated mice showed cognitive deficits, prepulse inhibition (PPI) deficits, reduced BDNF-TrkB signaling, immunoreactivity of parvalbumin (PV) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the prelimbic (PrL) of medial PFC and CA1 of hippocampus.

Supplementation of a TrkB agonist 7,8-dihydroxyflavone (1 mg/mL in drinking water) during juvenile and adolescent stages could prevent these behavioral abnormalities, reduced BDNF-TrkB signaling in PFC and CA1, and immunoreactivity of PV and PGC-1α in the PrL of medial PFC and CA1 in the adult offspring from poly(I:C)-treated mice.

These findings suggest that early intervention by a TrkB agonist in subjects with ultra-high risk for psychosis may reduce the risk of subsequent transition to schizophrenia.

Prenatal infection could be implicated in the etiology of schizophrenia1,2,3,4.

Late adolescence and early adulthood are peak times for the onset of schizophrenia as this period generally exposes substantial neurobiological changes in the brain5,6,7.

Cognitive impairment and social disabilities are often present before the onset of psychosis6,8,9,10. Thus, there is increasing interest in the potential benefit of early pharmacological intervention in schizophrenia11.

Maternal immune activation (MIA) in rodents has a great impact on brain development and behavioral abnormalities in their offspring3,12,13,14.

The offspring of prenatal rodents exposed to polyriboinosinic-polyribocytidylic acid [poly(I:C)] mimics schizophrenia- behavioral abnormalities in adulthood14,15. These deleterious effects in the offspring after MIA can be prevented by treatment with antipsychotics (e.g.

, clozapine and risperidone) during the juvenile period16,17. However, early treatments with antipsychotics during juvenile and adolescent stages caused long-term changes in cognition and neurobiology18,19.

Thus, the use of antipsychotics during these stages has detrimental side effects on the neurodevelopment process in humans. Therefore, it is necessary to develop safe drugs for preventing the onset of schizophrenia.

Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin receptor kinase B (TrkB) signaling plays a key role in brain neurodevelopment20,21,22. Decreased serum BDNF levels have been found in first-episode or chronic patients with schizophrenia23,24.

Furthermore, the reduction of expression of BDNF and TrkB receptor has been found in the prefrontal cortex and hippocampus of patients with schizophrenia25,26. The deficits in hippocampal BDNF expression are also found in placentas and offspring after maternal poly(I:C) exposure during pregnancy in rodents12,27.

These findings all suggest that decreased BDNF-TrkB signaling plays a role in the pathophysiology of schizophrenia. The TrkB agonist 7,8-dihydroxyflavone (7,8-DHF)28 has shown neuroprotective and cognitive enhancing effects in animal models29,30,31.

Therefore, it is of great interest to examine whether supplementation with 7,8-DHF during juvenile and adolescent stages can prevent the onset of schizophrenia- behavioral abnormalities at adulthood in MIA offspring.

In the present study, we investigated whether the offspring of mice exposed to poly(I:C) in the prenatal period show abnormal behaviors, BDNF-TrkB signaling, immunoreactivity of parvalbumin (PV) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the brain regions, which are implicated in the pathophysiology of schizophrenia25,26,32,33. Furthermore, we examined whether supplementation with 7,8-DHF during juvenile and adolescent stages can prevent abnormal behaviors, decreased BDNF-TrkB signaling, and PV and PGC-1α immunoreactivity in adult MIA offspring.

We examined whether offspring from prenatal mice exposed to poly(I:C) could cause abnormal behaviours and BDNF-TrkB signaling in the brain regions at juvenile stage (4–5- weeks old) (Fig. 1a). In the locomotion test (LMT), there was no difference between poly(I:C)-treated offspring and controls (P > 0.05) (Fig. 1b).

The MANOVA analysis of PPI data did not reveal significant effects between two groups (Wilks lambda = 0.874, P = 0.44) (Fig. 1c). In the novel object recognition test (NORT), there were no difference between poly(I:C)-treated group and control group in the training session (P > 0.05).

However, in the retention session, exploratory preference of poly(I:C)-treated group was significantly lower than that of controls (P 

Source: https://www.nature.com/articles/srep36087

7,8-Dihydroxyflavone Supplement Review, Dosage & Side Effects

12 Benefits of 7,8-Dihydroxyflavone (7,8-DHF) + Side Effects

The flavone 7,8-Dihydroxyflavone, which is isolated from the leaves of primula and Godmania aesculifolia trees, has been found to exhibit neuroprotective properties.

In laboratory and animal studies, 7,8-Dihydroxyflavone has been shown to mimic the function of an important chemical secreted in the brain. This chemical, brain-derived neurotrophic factor (BDNF), plays a role in the development and protection of brain cells.

The 7,8-Dihydroxyflavone molecule was first identified in 2010 while scientists were screening compounds looking for ones that prevented neural cell death.

While studies on animals suggest that 7,8-DHF may have some benefits in cognitive function and other areas, no human evidence yet exists. Most of the currently available research has been conducted in mouse models.

The molecule, in supplement form, is being anecdotally studied by reviewers in the amateur nootropic arena.

The potential nootropic effects of 7,8-DHF have receive a lot of attention in animal and in vitro studies, but there is no currently available human research data.

Flavonoids and flavones, in general, have been found to support cognitive function and brain cell health in both humans and animals. Flavonoids act as antioxidants and antimicrobial compounds. Other examples include EGCG in Green Tea Extract, proanthocyanidins, quercitrin, rutin and polyphenols in wine.

7,8-Dihydroxyflavone is purported to exhibit similar effects as other flavones, in addition to mimicking the effects of BDNF in the brain. This natural compound has been shown to activate tropomyosin-related kinase B (TrkB) receptors in the same way as brain derived neurotrophic factor.

BDNF has been generally linked to the concept of neuroplasticity and the ability of brain cells to grow and form new connections. More research is needed to demonstrate therapeutic effects, but there is interest in researching 7,8-DHF for conditions involving traumatic brain injury, post-traumatic stress disorder, cognitive decline and memory loss.

In a study where researchers injected 5 mg per kilogram of bodyweight into rats, it appeared that a single dose helped with memory in rats with stress-induced amnesia.

In healthy rats, the molecule appeared to improve learning and help aging rats retain cognition. However, in another study where 7,8-DHF’s effects on both stressed and unstressed rats were tested, there was no benefit to rats that had not undergone stress.

For anxiety, 7,8-DHF appeared to help with memory issues that resulted after rats were exposed to stress. When given 15 days after immobilization stress experiments, 7,8-DHF appeared to reduce the animal’s fear.

The molecule does not appear to have an effect on anxiety in rats where no external stressor was present.

Significantly more research is needed before determining whether this nootropic will be effective for humans or not.

Note: Do not confuse 4′-Dimethylamino-7,8-dihydroxyflavone (4′-DMA-7,8-DHF) with 7,8 DHF. These are two distinct compounds.

4′-DMA-7,8-DHF is a derivative which exhibits higher agonistic activity at the TrkB receptor, is more potent and has a longer duration of effects.

7,8-DHF has also been researched in animal models for its effects on mood, stroke recovery, weight control and addiction.

In a study on mice with depression that involved social defeat, symptoms appeared to be alleviated through injections of 10 mg/kg of bodyweight. The effect was similar in degree to the effects of the same amount of ketamine. However, the effects of 7,8-DHF wore off after six days while the mice who were given ketamine retained the effects.

In female rats with induced strokes, those that were given 7,8-DHF did not exhibit the same level of white-matter damage and cognitive issues. There was no benefit for male rats.

When rats were treated with 7,8-DHF before being subjected to a moderate impact injury, the substance appeared to have a protective effect.

In addition to the effects of BDNF on neurons in the brain, this protein is also secreted after exercise and controls weight gain by increasing the body’s use of energy.

Chemistry & Biology published a study in March, 2015 on the effects of 7,8-Dihydroxyflavone on weight loss and metabolism.

In a study on mice, they found that, in female mice, the molecule sped up metabolism and allowed the mice to eat high fat foods without weight gain or fat accumulation. However, there was no fat burning effect in male mice.

The researchers posited that the effects would be seen in an equivalent diet drug made for humans, as well. Researchers are not sure why the molecule affected females but not males, but think that a sex-specific hormone may be at play.

Preliminary research suggests that 7,8-DHF may protect against addiction. When the molecule was administered to rats that had been given cocaine, they were less ly to become addicted.

7,8-DHF increases nitric oxide signals in the body, which may reduce blood pressure. In one study on hypertensive rats, the molecule reduced blood pressure for about one hour. There was no effect on normal rats.

While it is not known whether 7,8-DHF improves skeletal muscle performance, mouse diaphragm muscle cells exposed to the substance saw increased neuromuscular transmission. There was no effect on muscle contraction or on muscle fatigue.

In in vitro studies, 7,8-DHF was able to stop oral and throat cancer cells from developing. The molecule also bound to a protein known as Sp1, which is overexpressed in cancer cells.

At the current time, there are no human studies on 7,8-DHF. While this flavone is extracted from a natural source, it is unclear whether therapeutic doses of this nootropic are safe or whether there may be side effects.

Because no human studies have been performed, the possible toxicity, side effects, contraindications and drug interactions of 7,8-DHF remain unknown.

In at least one 7,8-Dihydroxyflavone review, individuals report feeling more alert without the jitters that come from stimulants. Other reviewers state that they feel that their memory and concentration is improved. No reviewers have reported any noticeable side effects.

7,8-Dihydroxyflavone is available from a number of online Nootropic sales websites as well as on Amazon and eBay. It is most often found in capsule form.

Because of the lack of research on humans, websites state that they only sell 7,8-Dihydroxyflavone for non-clinical scientific research.

Rate This Article

(4 votes, average: 5.00 5, rated)

 Article last updated on: March 12th, 2018 by Nootriment 

Source: https://nootriment.com/78-dihydroxyflavone/

Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse

12 Benefits of 7,8-Dihydroxyflavone (7,8-DHF) + Side Effects

Open AccessCommunication

byAndrea Giacomini 1,†, Fiorenza Stagni 1,†, Marco Emili 1, Beatrice Uguagliati 1, Roberto Rimondini 2, Renata Bartesaghi 1,* and Sandra Guidi 1,*


Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy


Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy


Authors to whom correspondence should be addressed.

These Authors contributed equally to the work.

Antioxidants 2019, 8(6), 163; https://doi.org/10.3390/antiox8060163

Received: 18 April 2019 / Revised: 29 May 2019 / Accepted: 5 June 2019 / Published: 6 June 2019

View Full-TextDownload PDF No therapies currently exist for intellectual disability in Down syndrome (DS). In view of its similarities with DS, including learning and memory (L&M) defects, the Ts65Dn mouse model of DS is widely used for the design of therapy. 7,8-dihydroxyflavone (7,8-DHF), a flavonoid that targets the tropomyosin-related kinase B (TrkB) receptor of brain-derived neurotrophic factor (BDNF), exerts positive effects in various brain disease models. previous demonstration that administration of 7,8-DHF in the postnatal period P3-P15 restores hippocampal neurogenesis and spinogenesis, we sought to establish whether these effects translate into behavioral benefits after treatment cessation. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) during postnatal days P3-P15 did not show any L&M improvement at one month after treatment cessation, indicating that the effects of 7,8-DHF on the brain are ephemeral. evidence that chronic treatment with 7,8-DHF in juvenile Ts65Dn mice restores L&M, we sought to establish whether a similar effect is elicited in adulthood. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) for about 40 days starting from 4 months of age did not show any improvement in L&M. The results suggest that timing of therapy with 7,8-DHF is a critical issue for attainment of positive effects on the brain.View Full-Text

Keywords: Down syndrome; Ts65Dn mouse; Cognitive impairment; Therapy; Flavonoids; 7,8-dihydroxyflavone; Learning and memory Down syndrome; Ts65Dn mouse; Cognitive impairment; Therapy; Flavonoids; 7,8-dihydroxyflavone; Learning and memory

►▼Show Figures

div data-cycle-log=false>

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Share and Cite

MDPI and ACS Style

Giacomini, A.; Stagni, F.; Emili, M.; Uguagliati, B.; Rimondini, R.; Bartesaghi, R.; Guidi, S. Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse. Antioxidants 2019, 8, 163.

AMA Style

Giacomini A, Stagni F, Emili M, Uguagliati B, Rimondini R, Bartesaghi R, Guidi S. Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse. Antioxidants. 2019; 8(6):163.

Chicago/Turabian Style

Giacomini, Andrea; Stagni, Fiorenza; Emili, Marco; Uguagliati, Beatrice; Rimondini, Roberto; Bartesaghi, Renata; Guidi, Sandra. 2019. “Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse.” Antioxidants 8, no. 6: 163.

Show more citation formatsShow less citations formats

Article Metrics

Source: https://www.mdpi.com/2076-3921/8/6/163

Activation of TrkB/Akt signaling by a TrkB receptor agonist improves long-term histological and functional outcomes in experimental intracerebral hemorrhage

12 Benefits of 7,8-Dihydroxyflavone (7,8-DHF) + Side Effects

  1. 1.

    Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5:53–63.

  2. 2.

    Babadjouni RM, Radwanski RE, Walcott BP, Patel A, Durazo R, Hodis DM, Emanuel BA, Mack WJ. Neuroprotective strategies following intraparenchymal hemorrhage. J Neurointerv Surg. 2017;9:1202–7.

  3. 3.

    Wang YX, Yan A, Ma ZH, Wang Z, Zhang B, Ping JL, Zhu JS, Zhou Y, Dai L. Nuclear factor-kappaB and apoptosis in patients with intracerebral hemorrhage. J Clin Neurosci. 2011;18:1392–5.

  4. 4.

    Sun DB, Xu MJ, Chen QM, Hu HT. Significant elevation of serum caspase-3 levels in patients with intracerebral hemorrhage. Clin Chim Acta. 2017;471:62–7.

    • CAS
    • Article
    • Google Scholar
  5. 5.

    Krafft PR, Altay O, Rolland WB, Duris K, Lekic T, Tang J, Zhang JH. alpha7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3beta inhibition in a mouse model of intracerebral hemorrhage. Stroke. 2012;43:844–50.

    • CAS
    • Article
    • Google Scholar
  6. 6.

    Lee IN, Cheng WC, Chung CY, Lee MH, Lin MH, Kuo CH, Weng HH, Yang JT. Dexamethasone reduces brain cell apoptosis and inhibits inflammatory response in rats with intracerebral hemorrhage. J Neurosci Res. 2015;93:178–88.

    • CAS
    • Article
    • Google Scholar
  7. 7.

    Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495–516.

    • CAS
    • Article
    • Google Scholar
  8. 8.

    Sedlak TW, Oltvai ZN, Yang E, Wang K, Boise LH, Thompson CB, Korsmeyer SJ. Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. Proc Natl Acad Sci U S A. 1995;92:7834–8.

    • CAS
    • Article
    • Google Scholar
  9. 9.

    Hayakawa R, Hayakawa T, Takeda K, Ichijo H. Therapeutic targets in the ASK1-dependent stress signaling pathways. Proc Jpn Acad Ser B Phys Biol Sci. 2012;88:434–53.

    • CAS
    • Article
    • Google Scholar
  10. 10.

    Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011;1813:1978–86.

    • CAS
    • Article
    • Google Scholar
  11. 11.

    Harada H, Grant S. Apoptosis regulators. Rev Clin Exp Hematol. 2003;7:117–38.

  12. 12.

    Numakawa T, Suzuki S, Kumamaru E, Adachi N, Richards M, Kunugi H. BDNF function and intracellular signaling in neurons. Histol Histopathol. 2010;25:237–58.

  13. 13.

    Sussman MA. Mitochondrial integrity: preservation through Akt/Pim-1 kinase signaling in the cardiomyocyte. Expert Rev Cardiovasc Ther. 2009;7:929–38.

    • CAS
    • Article
    • Google Scholar
  14. 14.

    Marone R, Cmiljanovic V, Giese B, Wymann MP. Targeting phosphoinositide 3-kinase: moving towards therapy. Biochim Biophys Acta. 1784;2008:159–85.

  15. 15.

    Choi KS, Kim HJ, Do SH, Hwang SJ, Yi HJ. Neuroprotective effects of hydrogen inhalation in an experimental rat intracerebral hemorrhage model. Brain Res Bull. 2018;142:122–8.

    • CAS
    • Article
    • Google Scholar
  16. 16.

    Price RD, Milne SA, Sharkey J, Matsuoka N. Advances in small molecules promoting neurotrophic function. Pharmacol Ther. 2007;115:292–306.

    • CAS
    • Article
    • Google Scholar
  17. 17.

    Jang SW, Liu X, Yepes M, Shepherd KR, Miller GW, Liu Y, Wilson WD, Xiao G, Blanchi B, Sun YE, Ye K. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc Natl Acad Sci U S A. 2010;107:2687–92.

    • CAS
    • Article
    • Google Scholar
  18. 18.

    Kang JS, Choi IW, Han MH, Kim GY, Hong SH, Park C, Hwang HJ, Kim CM, Kim BW, Choi YH. The cytoprotective effects of 7,8-dihydroxyflavone against oxidative stress are mediated by the upregulation of Nrf2-dependent HO-1 expression through the activation of the PI3K/Akt and ERK pathways in C2C12 myoblasts. Int J Mol Med. 2015;36:501–10.

    • CAS
    • Article
    • Google Scholar
  19. 19.

    Wu CH, Hung TH, Chen CC, Ke CH, Lee CY, Wang PY, Chen SF. Post-injury treatment with 7,8-dihydroxyflavone, a TrkB receptor agonist, protects against experimental traumatic brain injury via PI3K/Akt signaling. PLoS One. 2014;9:e113397.

  20. 20.

    Devi L, Ohno M. 7,8-dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and BACE1 elevation in a mouse model of Alzheimer's disease. Neuropsychopharmacology. 2012;37:434–44.

    • CAS
    • Article
    • Google Scholar
  21. 21.

    Yuan D, Shen J, Yan Y, Wu X, Li A, Guo A, Wu Y, Duan C, Shen J, Tang C, et al. Upregulated expression of SSTR1 is involved in neuronal apoptosis and is coupled to the reduction of bcl-2 following intracerebral hemorrhage in adult rats. Cell Mol Neurobiol. 2014;34:951–61.

    • CAS
    • Article
    • Google Scholar
  22. 22.

    Wu CH, Chen CC, Lai CY, Hung TH, Lin CC, Chao M, Chen SF. Treatment with TO901317, a synthetic liver X receptor agonist, reduces brain damage and attenuates neuroinflammation in experimental intracerebral hemorrhage. J Neuroinflammation. 2016;13:62.

  23. 23.

    Chang CF, Chen SF, Lee TS, Lee HF, Chen SF, Shyue SK. Caveolin-1 deletion reduces early brain injury after experimental intracerebral hemorrhage. Am J Pathol. 2011;178:1749–61.

    • CAS
    • Article
    • Google Scholar
  24. 24.

    Wu CH, Shyue SK, Hung TH, Wen S, Lin CC, Chang CF, Chen SF. Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase reduces brain damage and attenuates neuroinflammation after intracerebral hemorrhage. J Neuroinflammation. 2017;14:230.

  25. 25.

    Saulle MF, Schambra HM. Recovery and rehabilitation after intracerebral hemorrhage. Semin Neurol. 2016;36:306–12.

  26. 26.

    Urday S, Kimberly WT, Beslow LA, Vortmeyer AO, Selim MH, Rosand J, Simard JM, Sheth KN. Targeting secondary injury in intracerebral haemorrhage–perihaematomal oedema. Nat Rev Neurol. 2015;11:111–22.

  27. 27.

    Xie L, Terrand J, Xu B, Tsaprailis G, Boyer J, Chen QM. Cystatin C increases in cardiac injury: a role in extracellular matrix protein modulation. Cardiovasc Res. 2010;87:628–35.

    • CAS
    • Article
    • Google Scholar
  28. 28.

    Stahl FR, Jung R, Jazbutyte V, Ostermann E, Todter S, Brixel R, Kemmer A, Halle S, Rose-John S, Messerle M, et al. Laboratory diagnostics of murine blood for detection of mouse cytomegalovirus (MCMV)-induced hepatitis. Sci Rep. 2018;8:14823.

  29. 29.

    Santos EW, de Oliveira DC, Hastreiter A, de Silva GB, de Beltran JSO, Tsujita M, Crisma AR, SMP N, Fock RA, Borelli P. Hematological and biochemical reference values for C57BL/6, Swiss Webster and BALB/c mice. Braz J Vet Res Anim Sci. 2016;53:138.

  30. 30.

    Takeda K, Matsuzawa A, Nishitoh H, Ichijo H. Roles of MAPKKK ASK1 in stress-induced cell death. Cell Struct Funct. 2003;28:23–9.

    • CAS
    • Article
    • Google Scholar
  31. 31.

    Goldman EH, Chen L, Fu H. Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation. J Biol Chem. 2004;279:10442–9.

    • CAS
    • Article
    • Google Scholar
  32. 32.

    Lu H, Huang H. FOXO1: a potential target for human diseases. Curr Drug Targets. 2011;12:1235–44.

    • CAS
    • Article
    • Google Scholar
  33. 33.

    Cheng PL, Song AH, Wong YH, Wang S, Zhang X, Poo MM. Self-amplifying autocrine actions of BDNF in axon development. Proc Natl Acad Sci U S A. 2011;108:18430–5.

    • CAS
    • Article
    • Google Scholar
  34. 34.

    Qureshi AI, Suri MF, Ostrow PT, Kim SH, Ali Z, Shatla AA, Guterman LR, Hopkins LN. Apoptosis as a form of cell death in intracerebral hemorrhage. Neurosurgery. 2003;52:1041–7 discussion 1047-1048.

  35. 35.

    van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9:167–76.

  36. 36.

    Zhang R, Yang J, Yuan J, Song B, Wang Y, Xu Y. The therapeutic value of bone marrow-derived endothelial progenitor cell transplantation after intracerebral hemorrhage in rats. Front Neurol. 2017;8:174.

  37. 37.

    Tamakoshi K, Kawanaka K, Onishi H, Takamatsu Y, Ishida K. Motor skills training improves sensorimotor dysfunction and increases microtubule-associated protein 2 mRNA expression in rats with intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2016;25:2071–7.

  38. 38.

    Grade S, Weng YC, Snapyan M, Kriz J, Malva JO, Saghatelyan A. Brain-derived neurotrophic factor promotes vasculature-associated migration of neuronal precursors toward the ischemic striatum. PLoS One. 2013;8:e55039.

    • CAS
    • Article
    • Google Scholar
  39. 39.

    Han XH, Cheng MN, Chen L, Fang H, Wang LJ, Li XT, Qu ZQ. 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cell death through modulating PI3K/Akt and JNK pathways. Neurosci Lett. 2014;581:85–8.

    • CAS
    • Article
    • Google Scholar
  40. 40.

    Subramaniam S, Unsicker K. ERK and cell death: ERK1/2 in neuronal death. FEBS J. 2010;277:22–9.

    • CAS
    • Article
    • Google Scholar
  41. 41.

    Jiang Q, Gu Z, Zhang G, Jing G. Diphosphorylation and involvement of extracellular signal-regulated kinases (ERK1/2) in glutamate-induced apoptotic- death in cultured rat cortical neurons. Brain Res. 2000;857:71–7.

    • CAS
    • Article
    • Google Scholar
  42. 42.

    Benvenisti-Zarom L, Chen-Roetling J, Regan RF. Inhibition of the ERK/MAP kinase pathway attenuates heme oxygenase-1 expression and heme-mediated neuronal injury. Neurosci Lett. 2006;398:230–4.

    • CAS
    • Article
    • Google Scholar
  43. 43.

    Fujimoto S, Katsuki H, Ohnishi M, Takagi M, Kume T, Akaike A. Thrombin induces striatal neurotoxicity depending on mitogen-activated protein kinase pathways in vivo. Neuroscience. 2007;144:694–701.

    • CAS
    • Article
    • Google Scholar
  44. 44.

    Fukunaga K, Kawano T. Akt is a molecular target for signal transduction therapy in brain ischemic insult. J Pharmacol Sci. 2003;92:317–27.

    • CAS
    • Article
    • Google Scholar
  45. 45.

    Su WS, Wu CH, Chen SF, Yang FY. Transcranial ultrasound stimulation promotes brain-derived neurotrophic factor and reduces apoptosis in a mouse model of traumatic brain injury. Brain Stimul. 2017;10:1032–41.

  46. 46.

    Uluc K, Kendigelen P, Fidan E, Zhang L, Chanana V, Kintner D, Akture E, Song C, Ye K, Sun D, et al. TrkB receptor agonist 7, 8 dihydroxyflavone triggers profound gender- dependent neuroprotection in mice after perinatal hypoxia and ischemia. CNS Neurol Disord Drug Targets. 2013;12:360–70.

    • CAS
    • Article
    • Google Scholar
  47. 47.

    Park HY, Park C, Hwang HJ, Kim BW, Kim GY, Kim CM, Kim ND, Choi YH. 7,8-Dihydroxyflavone attenuates the release of pro-inflammatory mediators and cytokines in lipopolysaccharide-stimulated BV2 microglial cells through the suppression of the NF-kappaB and MAPK signaling pathways. Int J Mol Med. 2014;33:1027–34.

    • CAS
    • Article
    • Google Scholar
  48. 48.

    Bramlett HM, Dietrich WD. Pathophysiology of cerebral ischemia and brain trauma: similarities and differences. J Cereb Blood Flow Metab. 2004;24:133–50.

  49. 49.

    Zhang X, Chen Y, Jenkins LW, Kochanek PM, Clark RS. Bench-to-bedside review: apoptosis/programmed cell death triggered by traumatic brain injury. Crit Care. 2005;9:66–75.

    • CAS
    • Article
    • Google Scholar
  50. 50.

    Mracsko E, Veltkamp R. Neuroinflammation after intracerebral hemorrhage. Front Cell Neurosci. 2014;8:388.

  51. 51.

    Fisher MJ. Brain regulation of thrombosis and hemostasis: from theory to practice. Stroke. 2013;44:3275–85.

  52. 52.

    Saba J, Turati J, Ramirez D, Carniglia L, Durand D, Lasaga M, Caruso C. Astrocyte truncated tropomyosin receptor kinase B mediates brain-derived neurotrophic factor anti-apoptotic effect leading to neuroprotection. J Neurochem. 2018;146:686–702.

    • CAS
    • Article
    • Google Scholar
  53. 53.

    Ai D, Shyy JY, Zhu Y. Linking an insect enzyme to hypertension: angiotensin II-epoxide hydrolase interactions. Kidney Int. 2010;77:88–92.

    • CAS
    • Article
    • Google Scholar
  54. 54.

    Chen SF, Tsai HJ, Hung TH, Chen CC, Lee CY, Wu CH, Wang PY, Liao NC. Salidroside improves behavioral and histological outcomes and reduces apoptosis via PI3K/Akt signaling after experimental traumatic brain injury. PLoS One. 2012;7:e45763.

    • CAS
    • Article
    • Google Scholar
  55. 55.

    Cheon SY, Kim EJ, Kim JM, Koo BN. Cell type-specific mechanisms in the pathogenesis of ischemic stroke: the role of apoptosis signal-regulating kinase 1. Oxidative Med Cell Longev. 2018;2018:2596043.

  56. 56.

    Fukunaga K, Shioda N. Pathophysiological relevance of forkhead transcription factors in brain ischemia. Adv Exp Med Biol. 2009;665:130–42.

    • CAS
    • Article
    • Google Scholar
  57. 57.

    Willhite CC, Katz PI. Toxicology updates. Dimethyl sulfoxide. J Appl Toxicol. 1984;4:155–60.

    • CAS
    • Article
    • Google Scholar
  58. 58.

    Iwamoto Y, Yang K, Clifton GL, Hayes RL. Liposome-mediated BDNF cDNA transfer in intact and injured rat brain. Neuroreport. 1996;7:609–12.

    • CAS
    • Article
    • Google Scholar
  59. 59.

    Xing Y, Wen CY, Li ST, Xia ZX. Non-viral liposome-mediated transfer of brain-derived neurotrophic factor across the blood-brain barrier. Neural Regen Res. 2016;11:617–22.

Source: https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0543-8

7,8-Dihydroxyflavone Powder | 7,8 DHF

12 Benefits of 7,8-Dihydroxyflavone (7,8-DHF) + Side Effects

(7 reviews) Write a Review Add to Cart SKU: ND1206A ACTIVE INGREDIENT: 7,8 Dihydroxyflavone ITEM TYPE: Powder QUANTITY PER BOTTLE: 1g, 2g, or 5g SERVINGS PER BOTTLE: 40, 80, or 200 SUGGESTED USE: As a dietary supplement, take 25mg of 7,8 DHF 1-2 times daily. It appears to be subject to extensive first-pass metabolism in the liver.

Due to improved bioavailability, sublingual administration (under the tongue) may be preferred. STORAGE: Store in a cool and dry place. Keep away from direct sunlight and heat. WARNING: Keep reach of children.

Do not take this or any other supplement if under the age of 18, pregnant or nursing a baby, or if you have any known or suspected medical conditions, and/or taking prescription drugs or over the counter medications. DISCLAIMER: Always consult with a qualified health physician before taking any new dietary supplement.

This product is not intended to diagnose, treat, cure, or prevent any diseases. These statements have not been evaluated by the Food and Drug Administration.

7,8-Dihydroxyflavone, also known as 7,8-DHF, is a natural flavone found in a number of species that can reach the brain and exert cognitive effects. It binds to the TrkB receptors in a similar way to BDNF, or brain derived neurotrophic factor. When the TrkB receptor is activated, neuroprotective and neurogenetive effects occur in neurons, which tend to affect the dendrites.

Dendrites are what reach out from the neurons into the synapse to participate in signaling with other neurons. 7,8-DHF has been shown to promote the growth of these dendrites, and to help restore communication between neurons in animal models.

Other natural extracts, polygala tenuifolia and bacopa monnieri  work in a similar fashion, but rather than binding directly to the TrkB receptor, they cause a release in BDNF, which then binds to the receptor. 7,8-DHF has also demonstrated a protective effect against apoptosis.

 7,8-DHF can cross the blood brain barrier, and act directly on brain TrkB receptors; which is something that peripheral administration of BDNF cannot do. As such, is is a very promising natural compound for cognitive enhancement.

7,8-Dihydroxyflavone Dosage

As a dietary supplement, take 25mg of 7,8 DHF 1-2 times daily. It appears to be subject to extensive first-pass metabolism in the liver. Due to improved bioavailability, sublingual administration (under the tongue) may be preferred. 

7,8-Dihydroxyflavone Reviews

To gain more insight about 7,8 DHF, read the 7,8-Dihydroxyflavone reviews and experiences below.

Where to Buy 7,8-Dihydroxyflavone Powder

Nootropics Depot offers 1 gram, 2 gram or 5 gram jars of 7,8 DHF Powder. Nootropics Depot's 7,8 Dihydroxyflavone powder has been lab-tested and verified for both product purity and identity.

Attention: These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

  • Good material . Dosage of 50-100mg. My stacks are pretty complex and ever-changing so sometimes tough to get a read on effects of specific substance but seem to have experienced some good effects. I have ordered material from Nootropics Depot a few times now and very impressed with quality , service and good selection of interesting and relevant products.
  • Unfortunately I was unable to notice any difference in memory, intuition, reaction processing or comprehension after 5 months of supplementation at the recommended dosages. I really was hoping to have discovered the proverbial 'fountain of youth', but for me, I was unaffected. I wish i could leave a comment without a rating, but since I cannot I did rate it 5 stars.I hope that my experience doesn't jade anyone else's opinion regarding 7,8-DiHdroxy, since so many have had a very positive outcome with this flavone.
  • Good material . Dosage of 50-100mg. My stacks are pretty complex and ever-changing so sometimes tough to get a read on effects of specific substance but seem to have experienced some good effects. I have ordered material from Nootropics Depot a few times now and very impressed with quality , service and good selection of interesting and relevant products.
  • Unfortunately I was unable to notice any difference in memory, intuition, reaction processing or comprehension after 5 months of supplementation at the recommended dosages. I really was hoping to have discovered the proverbial 'fountain of youth', but for me, I was unaffected. I wish i could leave a comment without a rating, but since I cannot I did rate it 5 stars.I hope that my experience doesn't jade anyone else's opinion regarding 7,8-DiHdroxy, since so many have had a very positive outcome with this flavone.
  • so, I just put this powder under the tongue? or is a different product for sublingualND Admin: Yes, this can be used sublingually.
  • I am blown away by its emotional naturalizing effect. otherwise I have problems addressing issues that are emotionally stressing. But this compound removes the apathy or the unwillingness to deal with the stuff that causes stress.
  • It has kept my “central sleep apnea” under control. Darn near cured it! Sublingual use of 25mg! prior to sleeptime.
  • 7,8 dhf has exceeded my expectations. If you are feeling in a funk this can help get through it
  • I was not sure if the placebo effect was going on the first day. But after a couple days, I have noticed memory recall to be better. I also had better focus and did not find myself bouncing around to a bunch of misc. tasks and was able to focus on the task at hand.I am not sure about tolerance yet, but I will probably only use on the days I really need to get stuff done. Seems to be a great add-on to my other stacks

Source: https://nootropicsdepot.com/7-8-dihydroxyflavone-powder-dhf/

12 Benefits of 7,8-Dihydroxyflavone (7,8-DHF) + Side Effects

12 Benefits of 7,8-Dihydroxyflavone (7,8-DHF) + Side Effects

7,8-DHF is an investigational plant compound and a new nootropic. It has attracted a lot of attention in recent years because it targets a brain receptor that helps grow new neurons. Learn about its potential here.

What Is 7,8-Dihydroxyflavone?

7,8-Dihydroxyflavone (7,8-DHF) is a flavone found in plants. It was discovered while searching for molecules that imitate the function of brain-derived neurotrophic factor (BDNF) [1, 2].

BDNF promotes the growth of neurons and synapses (synaptogenesis) and is very important for normal brain function. Lower amounts of BDNF are observed in diseases such as depression, Alzheimer’s, Parkinson’s, and schizophrenia [1, 3, 4].

Studies in animals show that 7,8-DHF could potentially help with brain repair, long-term memory, depression, and neurodegenerative diseases. However, studies in humans have not yet begun [2].

Mechanism of Effect

7,8-DHF mimics the effects of brain-derived neurotrophic factor (BDNF) in brain cells by activating tropomyosin-related kinase B (TrkB) receptors, the typical target of BDNF [5].

The therapeutic potential of BDNF is restricted due to its short half-life (less than 10 minutes) and its inability to cross the blood-brain barrier because of its large size. Un BDNF 7,8-DHFis able to penetrate the blood-brain barrier and enter the central nervous system (CNS) [1].

7,8-DHF also increases the production of Nrf2. Nrf2 increases antioxidants enzymes such as heme oxygenase 1 (HO-1) and also enzymes that repair DNA (8-oxoguanine DNA glycosylase-1 – OGG1) [6, 7].

Antioxidant Activity

7,8-DHF rescues cells from damage and death caused by oxidative stress [8].

Cells do not need to have the TrkB receptor to be protected [8].

In this case, 7,8-DHF:

R13 in Alzheimer’s Disease

Because of the relatively low apparent bioavailability of 7,8-DHF (about 5% in mice), researchers are currently developing prodrugs that can be converted to 7,8-DHF once inside the body. The most promising of these is currently known as R13, which has eliminated plaques associated with Alzheimer’s disease in the brains of living mice [12, 13].

R13 has not yet been tested in humans, and we do not recommend using it until such studies are conducted.

Animal & Cell Research on 7,8-Dihydroxyflavone

No clinical evidence supports the use of 7,8,-DHP for any health condition, as all research thus far has been preclinical. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

1) Memory and Learning

7,8-DHF improved object recognition (a test used to determine learning and memory) in healthy rats when given immediately following and three hours after learning. It also improved memory in mice with dementia [14].

In rat models of post-traumatic stress disorder (PTSD), 7,8-DHF prevented stress-related memory impairment [15, 16].

7,8-DHF also improved memory in aging rats [17, 18].

2) Brain Repair

7,8-DHF promoted the repair of damaged neurons [19].

It also increased the production of new neurons in the brains of adult mice after brain injury and promoted neuron growth in aged mice [20, 21].

Similarly, 7,8-DHF, along with exercise, improved brain function in rats that experienced traumatic brain injury [22].

3) Neuroprotection

7,8-DHF protected against stroke-related brain damage in mice. The beneficial effect was more pronounced in females [11, 23].

7,8-DHF also prevented neuronal damage in mice after traumatic brain injury [24].

4) Inflammation

7,8-DHF decreased the release of inflammatory factors in brain cells by blocking NF-κB [25].

7,8-DHF also reduced the levels of inflammation-causing nitric oxide, prostaglandin E2 (PGE2), TNF-alpha, and IL-6 in macrophages (white blood cells) [26].

Alzheimer’s Disease

In animal models for Alzheimer’s disease, 7,8-DHF [27, 28, 29, 14, 30]:

  • Reduced amyloid plaque formation
  • Reduced oxidative stress
  • Prevented loss of synapses
  • Prevented memory deficits and preserved cognitive function

However, another study found no benefits in treating mice with Alzheimer’s- brain damage with 7,8-DHF [31].

Parkinson’s Disease

7,8-DHF improved motor function and prevents the loss of dopamine-related neurons in a mouse model of Parkinson’s disease [32, 33, 34].

It also prevents the death of dopamine-sensitive neurons in monkey models of Parkinson’s disease [35].

Huntington’s Disease

7,8-DHF delayed the motor and cognitive impairment and prolonged survival in a mouse model of Huntington’s disease [36, 37].

Amyotrophic Lateral Sclerosis (ALS)

7,8-DHF improved motor deficits and neuron survival in a mouse model of ALS [38].

Multiple Sclerosis

7,8-DHF reduced disease severity in a mouse model of multiple sclerosis [39].


7,8-DHF decreased cognitive deficits and improved learning and memory in rat models of schizophrenia [40].

Infections in pregnancy and subsequent abnormal brain development can increase the risk of schizophrenia in offspring. Early use of 7,8-DHF decreased behavioral abnormalities and psychosis in mice offspring at risk of developing a schizophrenia- disorder [41, 42].

Down Syndrome

In a mouse model of down syndrome, early intervention with 7,8-DHF increased the production of new neurons (hippocampus) and improved learning and memory [43].

Fragile X Syndrome

Fragile X syndrome is a genetic condition. It causes a range of developmental problems including cognitive impairment and learning disabilities.

In a mouse model of fragile X syndrome, 7,8-DHF improved cognitive function and reduced spine abnormalities [44].

Rett Syndrome

Rett Syndrome is a non-inherited genetic brain disorder, mainly affecting girls. Symptoms include unusually slower growth, difficult coordination control, and language issues.

7,8-DHF improved symptoms in a mouse model of Rett syndrome [45].

6) Depression

7,8-DHF improved depression in mice that experienced social defeat [46].

It also reduced depressive behaviors in rodents experiencing chronic stress [47, 48].

7) Addiction

7,8-DHF decreased abnormalities in behavior and dopamine transport in mice on METH (methamphetamine) [49, 50].

7,8-DHF also reduced the rewarding effects of cocaine in mice [51].

8) Obesity

7,8-DHF reduced fat production and fat build-up by increasing antioxidant enzymes and neutralizing reactive oxygen species (ROS) [52].

In mice on a high-fat diet, 7,8-DHF increased muscle AMPK levels, increased whole-body energy expenditure, reduced fat, and improved insulin sensitivity [53].

Obesity in pregnancy can negatively impact the child via the placenta. 7,8-DHF improved placental characteristics and may, therefore, help decrease the negative effects of obesity in pregnancy [54].

9) Blood Pressure

When injected into rats with elevated blood pressure, 7,8-DHF caused an acute blood pressure reduction. When administered orally, there was still a decrease, but it was less pronounced [55].

10) Skin Aging

7,8-DHF decreased inflammation, increased collagen production, and increased antioxidant enzyme levels in aged human skin cells [56].

Cancer Research

7,8-DHF killed oral squamous cancer cells and skin cancer (melanoma) cells in dish studies; the potential relevance of such studies is unknown [57, 58].

Side Effects & Precautions

Due to a lack of human studies, the potential side effects of 7,8-DHF are unknown. However, users have anecdotally reported:

  • Overstimulation
  • Restlessness
  • Dizziness
  • Nausea
  • Irritability
  • Trouble sleeping

Drug Interactions

The possible drug interactions of 7,8-Dihydroxyflavone are unknown.

To avoid adverse effects and unexpected interactions, talk to your doctor before using 7,8-DHF.

Supplement Forms and Dosage

7,8-DHF can be purchased as capsules/pills, or powder.

There is no safe and effective dose of 7,8-DHF because no sufficiently powered study has been conducted to find one. The most common dosage in commercially available supplements is 10 – 30 mg per day.

Source: https://selfhacked.com/blog/7-8-dihydroxyflavone-benefits/