Icaritin opposes the development of social aversion after defeat stress via increases of GR mRNA and BDNF mRNA in mice.
Icariin is a major constituent of flavonoids isolated from Herba Epimedii. Several previous studies have demonstrated the antidepressant-like effects of icariin. After oral administration of icariin, 19 metabolites of icariin were detected in rat plasma. Icaritin is one such of metabolite of icariin. In this study, a chronic social defeat protocol is used as a mouse model for depression, and the effects of icaritin administration on social avoidance are investigated. The data indicates that icaritin (5mg/kg and 10mg/kg) oral administration opposes the development of social aversion after defeat stress. In vitro corticosterone sensitivity assay demonstrated that icaritin partially restored social defeat-induced impairment of glucocorticoid sensitivity. The expressions of GR mRNA and BDNFmRNA in the hippocampus were increased after icaritin treatment. Meanwhile, the social defeat-induced increases in CRH mRNA in hypothalamus were restored by icaritin administration. Our data also suggests that icaritin administration remarkably attenuated the increases in serum IL-6 and TNF-α level that occur following exposure to social defeat. In conclusion, icaritin is a novel antidepressant. It partially restored social defeat-induced impairment of glucocorticoid sensitivity, HPA axis hyperactivity. These effects are at least partially attributed to normalization of the GR function and increases in BDNF expression.
Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China.
Xiao
X
Wu
Jinfeng
J
Wu
Shijin
S
Xia
Bei
B
Li
Jingcheng
J
Dong
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012930:Social Dominance; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D005419:Flavonoids; D015850:Interleukin-6; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; C499403:icaritin
BDNF; Depression; GR; HPA axis; Icaritin