title: Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats.
abstract: Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction.
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China; Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China; Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Meng-Juan
authors.initials: MJ
authors.lastname: Gong
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China; Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China; Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China; Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China; Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Shu-mei
authors.initials: SM
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China; Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China; Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Sheng-wang
authors.initials: SW
authors.lastname: Liang
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China; Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, Guangdong Pharmaceutical University, Guangzhou 510006, China; Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: zouzhongjie@139.com.
authors.forename: Zhong-jie
authors.initials: ZJ
authors.lastname: Zou
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology*; D003863:Depression / Q000139:chemically induced* / Q000188:drug therapy*; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism; D013550:Swimming / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D005419:Flavonoids; C056599:icariin; D003345:Corticosterone
keywords: Brain-derived neurotrophic factor; Corticosterone; Depression; Icariin; Metabonomics