In 2017, evidence was published suggesting that tropoflavin and various other reported small-molecule TrkB agonists might not actually be direct agonists of the TrkB and might be mediating their observed effects by other means.[31][32]
Tropoflavin has been found to act as a weak
aromatase inhibitorin vitro (Ki = 10 μM),[33] though there is evidence to suggest that this might not be the case in vivo.[5] In addition, it has been found to inhibit
aldehyde dehydrogenase and
estrogen sulfotransferasein vitro (Ki = 35 μM and 1–3 μM, respectively), although similarly to the case of aromatase, these activities have not yet been confirmed in vivo.[5] Unlike many other
flavonoids, tropoflavin does not show any inhibitory activity on
17β-hydroxysteroid dehydrogenase.[34] Tropoflavin has also been observed to possess in vitroantiestrogenic effects at very high concentrations (Ki = 50 μM).[35][36]
^
abUS application 20150274692, Keqiang Ye, "7,8-Dihydoxyflavone and 7,8-substituted flavone derivatives, compositions, and methods related thereto", published 2015-10-01, assigned to Emory University
^
abZeng Y, Wang X, Wang Q, Liu S, Hu X, McClintock SM (2013). "Small molecules activating TrkB receptor for treating a variety of CNS disorders". CNS Neurol Disord Drug Targets. 12 (7): 1066–77.
doi:
10.2174/18715273113129990089.
PMID23844685.
^Yang YJ, Li YK, Wang W, Wan JG, Yu B, Wang MZ, Hu B (2014). "Small-molecule TrkB agonist 7,8-dihydroxyflavone reverses cognitive and synaptic plasticity deficits in a rat model of schizophrenia". Pharmacol. Biochem. Behav. 122: 30–6.
doi:
10.1016/j.pbb.2014.03.013.
PMID24662915.
S2CID12198275.
^Wang B, Wu N, Liang F, Zhang S, Ni W, Cao Y, Xia D, Xi H (2014). "7,8-dihydroxyflavone, a small-molecule tropomyosin-related kinase B (TrkB) agonist, attenuates cerebral ischemia and reperfusion injury in rats". J. Mol. Histol. 45 (2): 129–40.
doi:
10.1007/s10735-013-9539-y.
PMID24045895.
S2CID10671354.
^Tian M, Zeng Y, Hu Y, Yuan X, Liu S, Li J, Lu P, Sun Y, Gao L, Fu D, Li Y, Wang S, McClintock SM (2015). "7, 8-Dihydroxyflavone induces synapse expression of AMPA GluA1 and ameliorates cognitive and spine abnormalities in a mouse model of fragile X syndrome". Neuropharmacology. 89: 43–53.
doi:
10.1016/j.neuropharm.2014.09.006.
PMID25229717.
S2CID38120522.
^Foti M, Piattelli M, Baratta MT, Ruberto G (1996). "Flavonoids, Coumarins, and Cinnamic Acids as Antioxidants in a Micellar System. Structure−Activity Relationship†". Journal of Agricultural and Food Chemistry. 44 (2): 497–501.
doi:
10.1021/jf950378u.
ISSN0021-8561.
^Chen J, Chua KW, Chua CC, Yu H, Pei A, Chua BH, Hamdy RC, Xu X, Liu CF (2011). "Antioxidant activity of 7,8-dihydroxyflavone provides neuroprotection against glutamate-induced toxicity". Neurosci. Lett. 499 (3): 181–5.
doi:
10.1016/j.neulet.2011.05.054.
PMID21651962.
S2CID36661121.
^Han X, Zhu S, Wang B, Chen L, Li R, Yao W, Qu Z (2014). "Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity". Neurochem. Int. 64: 18–23.
doi:
10.1016/j.neuint.2013.10.018.
PMID24220540.
S2CID24439864.
^Ren Q, Zhang JC, Ma M, Fujita Y, Wu J, Hashimoto K (2014). "7,8-Dihydroxyflavone, a TrkB agonist, attenuates behavioral abnormalities and neurotoxicity in mice after administration of methamphetamine". Psychopharmacology. 231 (1): 159–66.
doi:
10.1007/s00213-013-3221-7.
PMID23934209.
S2CID17118439.
^Le Bail JC, Laroche T, Marre-Fournier F, Habrioux G (November 1998). "Aromatase and 17beta-hydroxysteroid dehydrogenase inhibition by flavonoids". Cancer Letters. 133 (1): 101–6.
doi:
10.1016/S0304-3835(98)00211-0.
PMID9929167.
^Le Bail JC, Varnat F, Nicolas JC, Habrioux G (1998). "Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids". Cancer Lett. 130 (1–2): 209–16.
doi:
10.1016/S0304-3835(98)00141-4.
PMID9751276.
^Pouget C, Lauthier F, Simon A, Fagnere C, Basly JP, Delage C, Chulia AJ (2001). "Flavonoids: structural requirements for antiproliferative activity on breast cancer cells". Bioorg. Med. Chem. Lett. 11 (24): 3095–7.
doi:
10.1016/S0960-894X(01)00617-5.
PMID11720850.
^Feng P, Akladious AA, Hu Y, Raslan Y, Feng J, Smith PJ (October 2015). "7,8-Dihydroxyflavone reduces sleep during dark phase and suppresses orexin A but not orexin B in mice". Journal of Psychiatric Research. 69: 110–9.
doi:
10.1016/j.jpsychires.2015.08.002.
PMID26343602.
In 2017, evidence was published suggesting that tropoflavin and various other reported small-molecule TrkB agonists might not actually be direct agonists of the TrkB and might be mediating their observed effects by other means.[31][32]
Tropoflavin has been found to act as a weak
aromatase inhibitorin vitro (Ki = 10 μM),[33] though there is evidence to suggest that this might not be the case in vivo.[5] In addition, it has been found to inhibit
aldehyde dehydrogenase and
estrogen sulfotransferasein vitro (Ki = 35 μM and 1–3 μM, respectively), although similarly to the case of aromatase, these activities have not yet been confirmed in vivo.[5] Unlike many other
flavonoids, tropoflavin does not show any inhibitory activity on
17β-hydroxysteroid dehydrogenase.[34] Tropoflavin has also been observed to possess in vitroantiestrogenic effects at very high concentrations (Ki = 50 μM).[35][36]
^
abUS application 20150274692, Keqiang Ye, "7,8-Dihydoxyflavone and 7,8-substituted flavone derivatives, compositions, and methods related thereto", published 2015-10-01, assigned to Emory University
^
abZeng Y, Wang X, Wang Q, Liu S, Hu X, McClintock SM (2013). "Small molecules activating TrkB receptor for treating a variety of CNS disorders". CNS Neurol Disord Drug Targets. 12 (7): 1066–77.
doi:
10.2174/18715273113129990089.
PMID23844685.
^Yang YJ, Li YK, Wang W, Wan JG, Yu B, Wang MZ, Hu B (2014). "Small-molecule TrkB agonist 7,8-dihydroxyflavone reverses cognitive and synaptic plasticity deficits in a rat model of schizophrenia". Pharmacol. Biochem. Behav. 122: 30–6.
doi:
10.1016/j.pbb.2014.03.013.
PMID24662915.
S2CID12198275.
^Wang B, Wu N, Liang F, Zhang S, Ni W, Cao Y, Xia D, Xi H (2014). "7,8-dihydroxyflavone, a small-molecule tropomyosin-related kinase B (TrkB) agonist, attenuates cerebral ischemia and reperfusion injury in rats". J. Mol. Histol. 45 (2): 129–40.
doi:
10.1007/s10735-013-9539-y.
PMID24045895.
S2CID10671354.
^Tian M, Zeng Y, Hu Y, Yuan X, Liu S, Li J, Lu P, Sun Y, Gao L, Fu D, Li Y, Wang S, McClintock SM (2015). "7, 8-Dihydroxyflavone induces synapse expression of AMPA GluA1 and ameliorates cognitive and spine abnormalities in a mouse model of fragile X syndrome". Neuropharmacology. 89: 43–53.
doi:
10.1016/j.neuropharm.2014.09.006.
PMID25229717.
S2CID38120522.
^Foti M, Piattelli M, Baratta MT, Ruberto G (1996). "Flavonoids, Coumarins, and Cinnamic Acids as Antioxidants in a Micellar System. Structure−Activity Relationship†". Journal of Agricultural and Food Chemistry. 44 (2): 497–501.
doi:
10.1021/jf950378u.
ISSN0021-8561.
^Chen J, Chua KW, Chua CC, Yu H, Pei A, Chua BH, Hamdy RC, Xu X, Liu CF (2011). "Antioxidant activity of 7,8-dihydroxyflavone provides neuroprotection against glutamate-induced toxicity". Neurosci. Lett. 499 (3): 181–5.
doi:
10.1016/j.neulet.2011.05.054.
PMID21651962.
S2CID36661121.
^Han X, Zhu S, Wang B, Chen L, Li R, Yao W, Qu Z (2014). "Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity". Neurochem. Int. 64: 18–23.
doi:
10.1016/j.neuint.2013.10.018.
PMID24220540.
S2CID24439864.
^Ren Q, Zhang JC, Ma M, Fujita Y, Wu J, Hashimoto K (2014). "7,8-Dihydroxyflavone, a TrkB agonist, attenuates behavioral abnormalities and neurotoxicity in mice after administration of methamphetamine". Psychopharmacology. 231 (1): 159–66.
doi:
10.1007/s00213-013-3221-7.
PMID23934209.
S2CID17118439.
^Le Bail JC, Laroche T, Marre-Fournier F, Habrioux G (November 1998). "Aromatase and 17beta-hydroxysteroid dehydrogenase inhibition by flavonoids". Cancer Letters. 133 (1): 101–6.
doi:
10.1016/S0304-3835(98)00211-0.
PMID9929167.
^Le Bail JC, Varnat F, Nicolas JC, Habrioux G (1998). "Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids". Cancer Lett. 130 (1–2): 209–16.
doi:
10.1016/S0304-3835(98)00141-4.
PMID9751276.
^Pouget C, Lauthier F, Simon A, Fagnere C, Basly JP, Delage C, Chulia AJ (2001). "Flavonoids: structural requirements for antiproliferative activity on breast cancer cells". Bioorg. Med. Chem. Lett. 11 (24): 3095–7.
doi:
10.1016/S0960-894X(01)00617-5.
PMID11720850.
^Feng P, Akladious AA, Hu Y, Raslan Y, Feng J, Smith PJ (October 2015). "7,8-Dihydroxyflavone reduces sleep during dark phase and suppresses orexin A but not orexin B in mice". Journal of Psychiatric Research. 69: 110–9.
doi:
10.1016/j.jpsychires.2015.08.002.
PMID26343602.