title: Chaihu-Shugan-San administration ameliorates perimenopausal anxiety and depression in rats.
abstract: Chaihu-Shugan-San (CSS) is a traditional Chinese herbal formula that is widely used for treating perimenopausal symptoms in China; however, its mechanisms remain unknown. The present study was designed to investigate potential CSS mechanisms in rats with unpredicted chronic mild stress (UCMS) and normally aging rats (52 weeks of age). We performed the sucrose consumption test along with the forced swimming test to confirm depression-like behavior and the open field test (OFT) to confirm anxiety-like behavior in the animals. In addition, we used an enzyme-linked immunosorbent assay to measure serum and hippocampal estradiol (E2) levels and a quantitative real-time polymerase chain reaction to assess hippocampal mRNA levels of estrogen receptors (ERs) α and β as well as G protein-coupled receptor 30 (GPR30). We found that CSS administration resulted in a significant increase in the ratio of hippocampal ERα and ERβ mRNA (ERα/ERβ ratio) in UCMS rats (p<0.001). However, no significant changes were observed in E2 levels, ERα mRNA expression, and GPR30 mRNA expression. In contrast, changes in ERα/ERβ mRNA ratio were sensitively associated with changes in mood states in the animal models. These findings suggest that enhancement of ERα/ERβ ratio may play a role in the pharmacological mechanisms of CSS. Furthermore, this ratio can be employed as a potential index for evaluating mood states in animal models and can be considered as a therapeutic target for perimenopausal anxiety and depression in the future.
authors.affiliation: Research base of TCM syndrome, Fujian University of Traditional Chinese Medicine, Minhou Fuzhou City, P.R of China.
authors.forename: Shujiao
authors.initials: S
authors.lastname: Chen
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Asakawa
authors.forename: Shanshan
authors.initials: S
authors.lastname: Ding
authors.forename: Linghong
authors.initials: L
authors.lastname: Liao
authors.forename: Lingyuan
authors.initials: L
authors.lastname: Zhang
authors.forename: Jianying
authors.initials: J
authors.lastname: Shen
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Hiroki
authors.initials: H
authors.lastname: Namba
authors.forename: Candong
authors.initials: C
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001007:Anxiety / Q000097:blood / Q000188:drug therapy*; D003863:Depression / Q000097:blood / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D047648:Perimenopause / Q000187:drug effects*; D010936:Plant Extracts / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C520305:Gper1 protein, rat; D010936:Plant Extracts; D043562:Receptors, G-Protein-Coupled; C497000:chaihu-shugan-san; D004958:Estradiol