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. Author manuscript; available in PMC: 2016 Mar 16.

Published in final edited form as: Pharmacology. 2013 Feb 21;91(3-4):185–200. doi: 10.1159/000346920

Fig. 5 — Chronic treatment with methylated derivatives displays a robust antidepressant effect. a Organic synthesis of methylated derivatives of flavonoids. b TrkB receptor activation by synthetic compounds C and D in vivo. The synthetic methylated compounds activate TrkB receptor in mouse brain after oral administration with 1 mg/kg dose at 2 h. c The methylated derivatives significantly reduce immobility in two antidepressant behavioral assays. Male C57BL/6J mice (8 mice/group) were orally administrated by gavage with 5 mg/kg H428, compounds C and D and vehicle solvent saline for 21 days and subjected to a FST (6 min, immobility recorded in the last 4 min with 2 min preswim). Data are presented as mean ± SEM. ANOVA revealed a significant difference between vehicle and either of the employed compounds (n = 8, * * p < 0.001 vs. vehicle) (left panel). The mice were subjected to the same treatment and analyzed by TST (6 min, immobility recorded in the last 4 min with 2 min preswim). Data are presented as mean ± SEM. ANOVA revealed a significant difference between vehicle and either of the employed compounds (n = 8, * * p < 0.001 vs. vehicle) (right panel). d Locomoter activity assay. Compound D but not compound C or H428 significantly elevated the mice locomotor activity compared to vehicle control after 21 days of chronic treatment. RT = Room temperature. * p < 0.05 ; * p < 0.01.

Fig. 5 — Chronic treatment with methylated derivatives displays a robust antidepressant effect. a Organic synthesis of methylated derivatives of flavonoids. b TrkB receptor activation by synthetic compounds C and D in vivo. The synthetic methylated compounds activate TrkB receptor in mouse brain after oral administration with 1 mg/kg dose at 2 h. c The methylated derivatives significantly reduce immobility in two antidepressant behavioral assays. Male C57BL/6J mice (8 mice/group) were orally administrated by gavage with 5 mg/kg H428, compounds C and D and vehicle solvent saline for 21 days and subjected to a FST (6 min, immobility recorded in the last 4 min with 2 min preswim). Data are presented as mean ± SEM. ANOVA revealed a significant difference between vehicle and either of the employed compounds (n = 8, * * p < 0.001 vs. vehicle) (left panel). The mice were subjected to the same treatment and analyzed by TST (6 min, immobility recorded in the last 4 min with 2 min preswim). Data are presented as mean ± SEM. ANOVA revealed a significant difference between vehicle and either of the employed compounds (n = 8, * * p < 0.001 vs. vehicle) (right panel). d Locomoter activity assay. Compound D but not compound C or H428 significantly elevated the mice locomotor activity compared to vehicle control after 21 days of chronic treatment. RT = Room temperature. * p < 0.05 ; * p < 0.01.