Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test.
We studied the effects of apigenin and 2,4,5-trimethoxycinnamic acid (TMCA) on the behavioral despair test (forced swimming test), and the central noradrenergic, dopaminergic and serotonergic activities in mice. Apigenin at intraperitoneal doses of 12.5 and 25 mg/kg significantly decreased the duration of immobility in the forced swimming test in mice. At 100 mg/kg, the duration of immobility was returned to the control level in the test. On the other hand, TMCA treatment (25-200 mg/kg, i.p.) failed to significantly alter the duration of immobility. Based on the behavioral data, we examined changes in the monoamine turnover in mice having been subjected to forced swimming for 40 min. The monoamine turnover was measured in seven brain regions. Forced swimming exposure induced a significant decrease in dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) in the striatum and amygdala and in 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytriptamine (5-HT) in the hypothalamus, and a significant increase in DOPAC/DA in the thalamus and hypothalamus and in 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG)/norepinephrine (NE) in the amygdala, frontal cortex, hypothalamus, and midbrain. Apigenin (25 mg/kg) treatment produced attenuation of forced swim test-induced decrease of DA turnover in the amygdala and increase of DA turnover in the hypothalamus. Furthermore, intraperitoneal administration of haloperidol (0.2 mg/kg), a dopamine D(2) antagonist, blocked the apigenin (25 mg/kg)-induced decrease in immobility in the forced swimming test. These behavioral and biochemical results indicate the antidepressant properties of apigenin, which may be mediated by the dopaminergic mechanisms in the mouse brain.
Nakazawa
Takahiro
T
Department of Phytochemistry, Tohoku Pharmaceutical University, Komatsushima, Sendai, Japan.
Yasuda
Takaaki
T
Ueda
Joji
J
Ohsawa
Keisuke
K
D000171:Acrolein / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D047310:Apigenin; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002934:Cinnamates / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007103:Immobilization / Q000502:physiology; D008297:Male; D051379:Mice; D031344:Perilla frutescens; D013550:Swimming / Q000523:psychology
C461723:2,4,5-trimethoxycinnamaldehyde; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D002934:Cinnamates; D005419:Flavonoids; C029010:cinnamic acid; D000171:Acrolein; D047310:Apigenin