title: Orcinol glucoside produces antidepressant effects by blocking the behavioural and neuronal deficits caused by chronic stress.
abstract: This study focused on the antidepressant potential of orcinol glucoside (OG) and its possible mechanisms of action. We established a depressed rat model using 3 consecutive weeks of chronic unpredictable mild stress (CUMS). The antidepressant-like effect of OG was revealed using the sucrose preference test, the open field test, the forced swimming test (FST), and the tail suspension test (TST). The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations and mRNA expression of corticotrophin-releasing hormone (CRH) in the hypothalamus. The protein expression levels of brain-derived neurotrophic factor (BDNF) and total phosphorylated-ERK1/2 were detected by western blot. The results showed that OG treatment (1.5, 3, or 6mg/kg) alleviated the depression-like behaviour of rats under CUMS, as indicated by the increased sucrose preference and the decreased immobility in both the FST and TST, although the rearing frequency in the open field test increased only in the group that received the lowest dose (1.5mg/kg OG). Rats that received OG treatment exhibited reduced serum CORT levels and CRH mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by OG treatment. Moreover, OG treatment upregulated the protein levels of BDNF and phosphorylated-ERK1/2 in the hippocampus, even above control levels. Our findings suggest that OG improved depressive behaviour in CUMS rats by downregulating HPA axis hyperactivity and increasing BDNF expression and ERK1/2 phosphorylation in the hippocampus.
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China.
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Ge
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Gao
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Cheng
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Lu
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China. Electronic address: ln0110@sina.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China. Electronic address: cfhchina@sohu.com.
authors.forename: Fei-Hu
authors.initials: FH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005518:Food Preferences; D005960:Glucosides / Q000627:therapeutic use*; D019417:Hindlimb Suspension; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012118:Resorcinols / Q000737:chemistry*; D013315:Stress, Psychological / Q000097:blood / Q000150:complications*; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D005960:Glucosides; D012118:Resorcinols; D013549:Sweetening Agents; C005282:orcinol; D013395:Sucrose; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
keywords: Antidepressant; Brain-derived neurotrophic factor (BDNF); Extracellular signal-regulated kinase (ERK); Hypothalamic–pituitary–adrenal (HPA) axis; Orcinol glucoside