Jung Eun Choi1, Dae-Myung Park2, Eunho Chun1, Jeong June Choi3, Ji Hye Seo3, Seunghyung Kim4, Jaemin Son1, Moonho Do5, Sun Yeou Kim5, Yang-Chun Park6, In Chul Jung7, Mirim Jin8. 1. Laboratory of Pharmacology, College of Korean Medicine, Daejeon University, Daejeon 34520, South Korea. 2. Department of Neuropsychiatry, Dunsan Korean Medicine Hospital of Daejeon University, Daejeon 35235, South Korea. 3. Laboratory of Molecular Medicine, College of Korean Medicine, Daejeon University, Daejeon 34520, South Korea. 4. Institute of Traditional Medicine and Bioscience, Daejeon University, Daejeon 34520, South Korea. 5. College of Pharmacy, Gachon University, Incheon 21999, South Korea. 6. Department of Internal Medicine, Daejeon Korean Medicine Hospital of Daejeon University, Daejeon 34623, South Korea. 7. Department of Neuropsychiatry, Dunsan Korean Medicine Hospital of Daejeon University, Daejeon 35235, South Korea. Electronic address: npjeong@dju.ac.kr. 8. Laboratory of Pharmacology, College of Korean Medicine, Daejeon University, Daejeon 34520, South Korea. Electronic address: mirimj@dju.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: So-ochim-tang-gamibang (SOCG) is a Korean herbal medicine formula that has been applied to treat depressive moods and depression associated somatoform pain. This decoction consists of Cyperus rotundus L. (Cyperi Rhizoma), Lindera aggregata (Sims) Kosterm. (Linderae Radix), Aquilaria agallochum (Lour.) Roxb. ex Finl. (Aquilariae Resinatum Lignum), Glycyrrhiza uralensis Fisch. (Glycyrrhizae Radix) Platycodon grandiflorum (Jacq.) A. DC. (Platycodi Radix), and Citrus aurantium L. (Aurantii Fructus). The aim of this study is to assess antidepressant-like effects of SOCG and to investigate its possible cellular and molecular mechanisms. MATERIAL AND METHODS: Using chronic restraint stress animal model, effects of SOCG on depressive-like behaviors, corticosterone, and hippocampal expressions of a neurotrophic factor and an apoptotic marker, were investigated. Mice were exposed to restraint stress 6h per day over a period of two weeks, and orally administrated either SOCG (30, 100, or 300mg/kg/day). The depressive-like behaviors were analyzed by forced swimming test and open field test. The serum levels of corticosterone were measured by enzyme-linked immunosorbent assay. Expressions of caspase-3 and BDNF in the hippocampus were analyzed by immunofluorescence. Further, effects of SOCG were examined in corticosterone-treated PC12 cells. Cellular toxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. Real-time PCR was applied to investigate the cellular expression levels of Bax, Bcl-2, and BDNF. The levels of caspase-3 and BDNF were examined by Western blotting. RESULTS: Administration of SOCG not only reduced immobility time of restraint-stressed mice in a dose-dependent manner, but also significantly increased the distance mice moved and the number of crossings in the open field test. Further, SOCG significantly reduced the serum level of corticosterone and expression of caspase-3, while increased expression of BDNF in vivo. SOCG increased cell viability in corticosterone treated PC12 cells, which was accompanied by decreased caspase-3 expression and the ratio of Bax/Bcl-2 mRNA expression as well as increased BDNF expression in vitro. CONCLUSIONS: Taken together, our data suggested that SOCG may have potential as an antidepressant agent controlling depressive behaviors and corticosterone-induced neuronal damage caused by chronic stress.
ETHNOPHARMACOLOGICAL RELEVANCE: So-ochim-tang-gamibang (SOCG) is a Korean herbal medicine formula that has been applied to treat depressive moods and depression associated somatoform pain. This decoction consists of Cyperus rotundus L. (Cyperi Rhizoma), Lindera aggregata (Sims) Kosterm. (Linderae Radix), Aquilaria agallochum (Lour.) Roxb. ex Finl. (Aquilariae Resinatum Lignum), Glycyrrhiza uralensis Fisch. (Glycyrrhizae Radix) Platycodon grandiflorum (Jacq.) A. DC. (Platycodi Radix), and Citrus aurantium L. (Aurantii Fructus). The aim of this study is to assess antidepressant-like effects of SOCG and to investigate its possible cellular and molecular mechanisms. MATERIAL AND METHODS: Using chronic restraint stress animal model, effects of SOCG on depressive-like behaviors, corticosterone, and hippocampal expressions of a neurotrophic factor and an apoptotic marker, were investigated. Mice were exposed to restraint stress 6h per day over a period of two weeks, and orally administrated either SOCG (30, 100, or 300mg/kg/day). The depressive-like behaviors were analyzed by forced swimming test and open field test. The serum levels of corticosterone were measured by enzyme-linked immunosorbent assay. Expressions of caspase-3 and BDNF in the hippocampus were analyzed by immunofluorescence. Further, effects of SOCG were examined in corticosterone-treated PC12 cells. Cellular toxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. Real-time PCR was applied to investigate the cellular expression levels of Bax, Bcl-2, and BDNF. The levels of caspase-3 and BDNF were examined by Western blotting. RESULTS: Administration of SOCG not only reduced immobility time of restraint-stressed mice in a dose-dependent manner, but also significantly increased the distance mice moved and the number of crossings in the open field test. Further, SOCG significantly reduced the serum level of corticosterone and expression of caspase-3, while increased expression of BDNF in vivo. SOCG increased cell viability in corticosterone treated PC12 cells, which was accompanied by decreased caspase-3 expression and the ratio of Bax/Bcl-2 mRNA expression as well as increased BDNF expression in vitro. CONCLUSIONS: Taken together, our data suggested that SOCG may have potential as an antidepressant agent controlling depressive behaviors and corticosterone-induced neuronal damage caused by chronic stress.
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