title: Genipin is active via modulating monoaminergic transmission and levels of brain-derived neurotrophic factor (BDNF) in rat model of depression.
abstract: Genipin, an important bioactive component from Gardenia jasminoides Eills, was demonstrated to possess antidepressant-like effects in a previous study. However, the molecular mechanism of antidepressant-like effects on genipin was not clear. The present study aimed to investigate the possible mechanism of antidepressant-like effects on genipin with a chronic unpredictable mild stress (CUMS)-induced depression model in rats. In CUMS-induced depressive rats, bodyweight and 1% sucrose consumption decreased significantly compared with the normal control group. Furthermore, these changes could be significantly reversed by genipin application. The levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) in the hippocampus decreased and the level of 5-hydroxyindole acetic acid (5-HIAA) increased in the CUMS-induced depressive rats. However, pre-treatments with genipin significantly increased the levels of 5-HT, NE and decreased the level of 5-HIAA in the hippocampus. The concentration of cAMP in the hippocampus was increased by genipin compared to the CUMS-exposed model group. The mRNA expressions of 5-hydroxytryptamine 1A receptor (5-HT1AR), cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in rats were decreased exposed to CUMS, which were reversed by genipin-treated rats exposed to CUMS. Compared to the CUMS-exposed model group, the mRNA expression of 5-hydroxytryptamine 2A receptor (5-HT(2A)R) was decreased significantly by genipin-treated rats. The mRNA and protein expression of CREB, BDNF were increased in genipin-treated rats compared to the CUMS-exposed model group. Moreover, the levels of corticosterone in serum were decreased by genipin-treated compared to the CUMS-exposed model group. These results suggest that the possible mechanism of antidepressant-like effects on genipin, at least in one part, resulted from monoaminergic neurotransmitter system and the potential dysfunctional regulation of the post-receptor signaling pathway, which particularly affected the 5-HT(1A)R, 5-HT(2A)R and BDNF levels in the hippocampus.
authors: Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Institute of Medical Equipment, Academy of Military Medical Sciences, Tianjin 300161, PR China.
authors: Q-S
authors: QS
authors: Wang
authors: Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China.
authors: J-S
authors: JS
authors: Tian
authors: Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. Electronic address: cuiyl@tju.edu.cn.
authors: Y-L
authors: YL
authors: Cui
authors: Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China.
authors: S
authors: S
authors: Gao
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D003863:Depression / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D039823:Iridoids / Q000494:pharmacology*; D008297:Male; D008517:Phytotherapy / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D039823:Iridoids; D011985:Receptors, Serotonin; D012701:Serotonin; C007834:genipin
keywords: antidepressant; brain-derived neurotrophic factor; chronic unpredictable mild stress; genipin; serotonin