Antidepressant-like behavioral and neurochemical effects of the citrus-associated chemical apigenin.
Apigenin is one type of bioflavonoid widely found in citrus fruits, which possesses a variety of pharmacological actions on the central nervous system. A previous study showed that acute intraperitoneal administration of apigenin had antidepressant-like effects in the forced swimming test (FST) in ddY mice. To better understand its pharmacological activity, we investigated the behavioral effects of chronic oral apigenin treatment in the FST in male ICR mice and male Wistar rats exposed to chronic mild stress (CMS). The effects of apigenin on central monoaminergic neurotransmitter systems, the hypothalamic-pituitary-adrenal (HPA) axis and platelet adenylyl cyclase activity were simultaneously examined in the CMS rats. Apigenin reduced immobility time in the mouse FST and reversed CMS-induced decrease in sucrose intake of rats. Apigenin also attenuated CMS-induced alterations in serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA) levels and 5-HIAA/5-HT ratio in distinct rat brain regions. Moreover, apigenin reversed CMS-induced elevation in serum corticosterone concentrations and reduction in platelet adenylyl cyclase activity in rats. These results suggest that the antidepressant-like actions of oral apigenin treatment could be related to a combination of multiple biochemical effects, and might help to elucidate its mechanisms of action that are involved in normalization of stress-induced changes in brain monoamine levels, the HPA axis, and the platelet adenylyl cyclase activity.
Yi
Li-Tao
LT
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.
Li
Jian-Mei
JM
Li
Yu-Cheng
YC
Pan
Ying
Y
Xu
Qun
Q
Kong
Ling-Dong
LD
D000262:Adenylyl Cyclases / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D047310:Apigenin / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D002957:Citrus / Q000737:chemistry*; D003345:Corticosterone / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013550:Swimming
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D047310:Apigenin; D000262:Adenylyl Cyclases; D003345:Corticosterone