Antidepressant-like effect of geniposide on chronic unpredictable mild stress-induced depressive rats by regulating the hypothalamus-pituitary-adrenal axis.
Geniposide as the major active component of Gardenia jasminoides Ellis has neuroprotective activity. This study elucidated the potential antidepressant-like effect of geniposide and its related mechanisms using a depression rat model induced by 3 consecutive weeks of chronic unpredictable mild stress (CUMS). Sucrose preference test, open field test (OFT) and forced swimming test (FST) were applied to evaluate the antidepressant effect of geniposide. Adrenocorticotropic hormone (ACTH) and corticosterone (CORT) serum levels, adrenal gland index and hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression were measured to assess the activity of hypothalamus-pituitary-adrenal (HPA) axis. Hypothalamic glucocorticoid receptor α (GRα) mRNA expression and GRα protein expression in hypothalamic paraventricular nucleus (PVN) were also determined by real-time PCR and immunohistochemistry, respectively. We found that geniposide (25, 50, 100mg/kg) treatment reversed the CUMS-induced behavioral abnormalities, as suggested by increased sucrose intake, improved crossing and rearing behavior in OFT, shortened immobility and prolonged swimming time in FST. Additionally, geniposide treatment normalized the CUMS-induced hyperactivity of HPA axis, as evidenced by reduced CORT serum level, adrenal gland index and hypothalamic CRH mRNA expression, with no significant effect on ACTH serum level. Moreover, geniposide treatment upregulated the hypothalamic GRα mRNA level and GRα protein expression in PVN, suggesting geniposide could recover the impaired GRα negative feedback on CRH expression and HPA axis. These aforementioned therapeutic effects of geniposide were essentially similar to fluoxetine. Our results indicated that geniposide possessed potent antidepressant-like properties that may be mediated by its effects on the HPA axis.
Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei 230032, Anhui, PR China.
Li
L
Cai
School of Pharmacy, Anhui Medical University, Hefei 230032, Anhui, PR China. Electronic address: aydlirong@163.com.
Rong
R
Li
School of Pharmacy, Anhui Medical University, Hefei 230032, Anhui, PR China.
Wen-jian
WJ
Tang
Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei 230032, Anhui, PR China.
Gang
G
Meng
Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei 230032, Anhui, PR China.
Xiang-yang
XY
Hu
School of Pharmacy, Anhui Medical University, Hefei 230032, Anhui, PR China.
Ting-ni
TN
Wu
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D039823:Iridoids / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013315:Stress, Psychological; D035501:Uncertainty
D000928:Antidepressive Agents; D019422:Dietary Sucrose; D039823:Iridoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C007835:geniposide; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
Antidepressant; Chronic unpredictable mild stress (CUMS); Depression; Geniposide; Glucocorticoid receptor α (GRα); Hypothalamic–pituitary–adrenal (HPA) axis