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Abstract Background So-ochim-tang-gamibang (SOCG) is a traditional Korean medicine frequently used for depression in the clinical field. In this study, we evaluated the potential genotoxicity of SOCG using three standard batteries of tests as part of a safety evaluation. Methods SOCG was evaluated for potential genotoxic effects using the standard three tests recommended by the Ministry of Food and Drug Safety (MFDS) of Korea. These tests were the bacterial reverse mutation test (Ames test), in vitro mammalian chromosomal aberration test using Chinese hamster lung cells, and in vivo micronucleus test using ICR mice. Results The Ames test with Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and the Escherichia coli strain WP2uvrA(pKM101) showed that SOCG did not induce gene mutations at any dose level in all of the strains. SOCG did not induce any chromosomal aberrations in the in vitro chromosomal aberration test (for both the 6 and 24 h test) and the in vivo micronucleus test. Conclusions Based on the results of these tests, it was concluded that SOCG does not exhibit any genotoxic risk under the experimental conditions of this study.

Abstract Background So-ochim-tang-gamibang (SOCG) is a decoction formula which has been used to improve mental activity in traditional Korean medicine. The present study was performed to evaluate whether the treatment of SOCG was involved in activating hippocampal neurons in mice which were subjected to chronic restraint stress (CRS). Methods Mice were subjected to CRS for 2 weeks to induce depressive-like behaviors. SOCG was orally administered for the same period. mRNA expression in the hippocampus was analyzed by RT-PCR. Levels of serotonin receptor 5-HT1AR in the hippocampus were determined by western blotting and by immunofluorescence staining in coronal brain sections. Cultured neurons were prepared from the dorsal root ganglia (DRG) in mice to examine the effects of CRS and SOCG treatment on neurite outgrowth. Depressive-like behaviors of experimental animals were measured by open field test (OFT) and forced swimming test (FST). Results mRNA levels of serotonin 1A and 1B receptors (5-HT1AR and 5-HT1BR) were decreased in the hippocampus of CRS animals and increased by SOCG treatment. Signals of 5-HT1AR protein in CA3 pyramidal cells were decreased by CRS but elevated back to levels in control animals after SOCG treatment. Phospho-Erk1/2 protein in CA3 cells showed similar pattern of changes as in 5-HT1AR, suggesting coordinated regulation after SOCG treatment in CRS animals. Axonal growth-associated protein GAP-43 levels were also decreased by CRS and then increased by SOCG treatment. In vivo administration of SOCG improved neurite outgrowth of primary DRG neurons from CRS animals and also increased 5-HT1AR protein signals. Behavioral tests of open field and forced swimming showed that immobility time periods were significantly decreased by SOCG treatment. Conclusions Our data suggest that SOCG treatment may increase synaptic responsiveness to serotonergic neuronal inputs by upregulating 5-HT1AR in the hippocampal neurons.

Ethnopharmacological relevance So-ochim-tang-gamibang (SOCG) is a traditional Korean medicine formulated to control internal energy flow (Qi) and has been prescribed to improve stress-induced depressive disorders. Aim of the study SOCG has been used in clinical practice for the last two decades and its efficacy against stress-induced thoracic pain has been suggested. Although SOCG has been used as an herbal formula in Korean medicine, its toxicity has not yet been evaluated. In this study, we evaluated the safety of SOCG through a 13-week general toxicity study in rats. Material and methods SOCG was administered by oral gavage to rats at doses of 0 (control), 800, 2000, and 5000 mg/kg/day over a 13-week period. Toxicity testing was conducted by evaluating mortality, clinical signs, body weight, food consumption, urinalysis, hematology, serum biochemistry, organ weight, necropsy, and histopathology compared with the concurrent control. Results SOCG-related changes were noted in clinical signs and urinalysis. The observed clinical signs were compound-colored stool and salivation. Urinalysis results revealed brown or amber colored urine and elevated levels of protein. However, these changes were not considered to be adverse. Conclusions The no-observed-adverse-effect-level of SOCG was determined to be above 5000 mg/kg in both male and female rats. The result of this study can lay the foundation for the application of SOCG in humans and prove useful for detailed investigations on the toxicity or pharmacological effects of SOCG. [ABSTRACT FROM AUTHOR]

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 6 h per day over a period of two weeks, and orally administrated either SOCG (30, 100, or 300 mg/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. [ABSTRACT FROM AUTHOR]

Background: So-ochim-tang-gamibang (SOCG) is a decoction formula which has been used to improve mental activity in traditional Korean medicine. The present study was performed to evaluate whether the treatment of SOCG was involved in activating hippocampal neurons in mice which were subjected to chronic restraint stress (CRS)., Methods: Mice were subjected to CRS for 2 weeks to induce depressive-like behaviors. SOCG was orally administered for the same period. mRNA expression in the hippocampus was analyzed by RT-PCR. Levels of serotonin receptor 5-HT1AR in the hippocampus were determined by western blotting and by immunofluorescence staining in coronal brain sections. Cultured neurons were prepared from the dorsal root ganglia (DRG) in mice to examine the effects of CRS and SOCG treatment on neurite outgrowth. Depressive-like behaviors of experimental animals were measured by open field test (OFT) and forced swimming test (FST)., Results: mRNA levels of serotonin 1A and 1B receptors (5-HT1AR and 5-HT1BR) were decreased in the hippocampus of CRS animals and increased by SOCG treatment. Signals of 5-HT1AR protein in CA3 pyramidal cells were decreased by CRS but elevated back to levels in control animals after SOCG treatment. Phospho-Erk1/2 protein in CA3 cells showed similar pattern of changes as in 5-HT1AR, suggesting coordinated regulation after SOCG treatment in CRS animals. Axonal growth-associated protein GAP-43 levels were also decreased by CRS and then increased by SOCG treatment. In vivo administration of SOCG improved neurite outgrowth of primary DRG neurons from CRS animals and also increased 5-HT1AR protein signals. Behavioral tests of open field and forced swimming showed that immobility time periods were significantly decreased by SOCG treatment., Conclusions: Our data suggest that SOCG treatment may increase synaptic responsiveness to serotonergic neuronal inputs by upregulating 5-HT1AR in the hippocampal neurons.