• Journal of Oriental Neuropsychiatry
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• v.30 no.3
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• pp.209-220
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• 2019

Objectives: As a general emotion, everyone can temporarily experience depression, but depressive disorder is a disease that excessively affects daily life. Among the various causes of depression, the deficiency of monoamine-based neurotransmitters such as serotonin and epinephrine are considered significant. Thus, antidepressants that target monoamines are used frequently. However, side effects such as nausea, vomiting, insomnia, anxiety, and sexual dysfunction are observed. Thus, it is necessary to develop a new therapeutic agent with fewer side effects. In this study, we investigated the antidepressant effect of JG02, used to treat depression by normalizing the flow of qi (氣) in Korean medicine. Methods: C57BL/6 mice were selected and randomly divided into six groups: normal, control, amitriptyline, and JG02 (50, 125, 250 mg/kg), respectively. Except for normal, depression was induced by applying restraint stress at the same time for six hours daily for 14 consecutive days. Saline, amitriptyline or JG02 samples were orally administered two hours before applying the stress. After that, a forced swimming test and an open field test were performed. Additionally, serum corticosterone, serotonin mRNA, BDNF mRNA, and protein in the hippocampal region were measured and compared. Results: JG02 decreased immobility time rate in the FST and increased the zone transition number and travel distance in the OFT. Also, JG02 inhibited the release of serum corticosterone, and increased serotonin, BDNF gene expression, and BDNF protein in the hippocampus. Conclusions: In this study, JG02 showed significant antidepressant effects on the chronic restraint stress mice model. When further research is performed based on JG02, the development of a new antidepressant is considered highly possible.

• Journal of Life Science
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• v.31 no.11
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• pp.995-1003
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• 2021

Chromatin remodeling regulates gene expression through epigenetic mechanisms. Aberrations in histone modification have been associated with depression-like behaviors in animal models. Additionally, growing evidence also indicates that epigenetic modification is associated with depression. p11 (S100A10) has been implicated in the pathophysiology of depression both in human and rodent models. In the present study, we investigated alterations in histone acetylation and methylation at the promoter of the p11 gene in the hippocampus of mice subjected to chronic unpredictable stress (CUS). C57BL/6 mice were exposed to CUS daily for 3 weeks. Depression-like behaviors were measured with the forced swimming test (FST). The levels of hippocampal p11 expression were analyzed by quantitative real-time polymerase chain reaction (PCR) and Western blotting. The levels of acetylated and methylated histone H3 at the promoter of p11 were measured by chromatin immunoprecipitation followed by real-time PCR. CUS-exposed mice displayed depression-like behaviors with prolonged immobility in FST. CUS led to significant decreases in the expression of p11 at both protein and mRNA levels. Meanwhile, there was a decrease in histone H3 acetylation (Ac-H3) and H3-K4 trimethylation (H3K4met3) and an increase in H3-K27 trimethylation (H3K27met3) at the p11 promoter. These results indicate that chronic stress causes the epigenetic suppression of p11 expression in the hippocampus.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.666-674
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• 2022

Background: Ginsenosides and their metabolites have antidepressant-like effects, but the underlying mechanisms remain unclear. We previously identified 14-3-3 ζ as one of the target proteins of 20 (S)-protopanaxadiol (PPD), a fully deglycosylated ginsenoside metabolite. Methods: Corticosterone (CORT) was administered repeatedly to induce the depression model, and PPD was given concurrently. The tail suspension test (TST) and the forced swimming test (FST) were used for behavioral evaluation. All mice were sacrificed. Golgi-cox staining, GSK 3β activity assay, and Western blot analysis were performed. In vitro, the kinetic binding analysis with the Biolayer Interferometry (BLI) was used to determine the molecular interactions. Results: TST and FST both revealed that PPD reversed CORT-induced behavioral deficits. PPD also ameliorated the CORT-induced expression alterations of hippocampal Ser9 phosphorylated glycogen synthase kinase 3β (p-Ser9 GSK 3β), Ser133 phosphorylated cAMP response element-binding protein (p-Ser133 CREB), and brain-derived neurotrophic factor (BDNF). Moreover, PPD attenuated the CORT-induced increase in GSK 3β activity and decrease in dendritic spine density in the hippocampus. In vitro, 14-3-3 ζ protein specifically bound to p-Ser9 GSK 3β polypeptide. PPD promoted the binding and subsequently decreased GSK 3β activity. Conclusion: These findings demonstrated the antidepressant-like effects of PPD on the CORT-induced mouse depression model and indicated a possible target-based mechanism. The combination of PPD with the 14-3-3 ζ protein may promote the binding of 14-3-3 ζ to p-GSK 3β (Ser9) and enhance the inhibition of Ser9 phosphorylation on GSK 3β kinase activity, thereby activating the plasticity-related CREBeBDNF signaling pathway.

• 한국체육학회지인문사회과학편
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• v.51 no.3
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• pp.437-445
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• 2012

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and manganese superoxide dismutase (MnSOD) has been hypothesized as a mediator in the activation of multiple pathways implicated in the pathogenesis of diabetic disease. The objective of this study was to understand the mechanism that aerobic exercise activate GAPDH and MnSOD in pancreatic cells. To achieve the purpose of this study, thirty male Sprague-Dawley rats were assigned to control group, diabetic group and diabetic exercise group. 10 rats were forced to exercise according to exercise protocol for 8weeks and 20 rats were untrained for control and diabetic group. Pancreatic tissue were extracted from the each. Expressions of GAPDH and MnSOD in diabetic pancreatic tissues were significantly decreased compare to control group. However, swimming (trained diabetic group) significantly increased expressions of GAPDH and MnSOD compare to diabetic group, respectively. In hyperglycemia, GAPDH and MnSOD in pancreatic cells is activated by aerobic exercise, and this inactivates multiple pathways implicated in the pathogenesis of diabetic disease. In conclusion, these findings suggest that increased activity of GAPDH and MnSOD by exercise have beneficial effects on mitochondrial dysfunction and arresting the progression of diabetic disease.

• Nutrition Research and Practice
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• v.17 no.4
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• pp.670-681
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is caused by reactive oxygen species and free radicals that accelerate inflammatory responses and exacerbate fatigue. Tormentic acid (TA) has antioxidant and anti-inflammatory properties. Thus, the aim of present study is to determine the fatigue-regulatory effects of TA in H₂O₂-stimulated myoblast cell line, C2C12 cells and treadmill stress test (TST) and forced swimming test (FST) animal models. MATERIALS/METHODS: In the in vitro study, C2C12 cells were pretreated with TA before stimulation with H₂O₂. Then, malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase (CK) activity, tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glycogen, and cell viability were analyzed. In the in vivo study, the ICR male mice were administered TA or distilled water orally daily for 28 days. FST and TST were then performed on the last day. In addition, biochemical analysis of the serum, muscle, and liver was performed. RESULTS: TA dose-dependently alleviated the levels of MDA, LDH, CK activity, TNF-α, and IL-6 in H₂O₂-stimulated C2C12 cells without affecting the cytotoxicity. TA increased the SOD and CAT activities and the glycogen levels in H₂O₂-stimulated C2C12 cells. In TST and FST animal models, TA decreased the FST immobility time significantly while increasing the TST exhaustion time without weight fluctuations. The in vivo studies showed that the levels of SOD, CAT, citrate synthase, glycogen, and free fatty acid were increased by TA administration, whereas TA significantly reduced the levels of glucose, MDA, LDH, lactate, CK, inflammatory cytokines, alanine transaminase, aspartate transaminase, blood urea nitrogen, and cortisol compared to the control group. CONCLUSIONS: TA improves fatigue by modulating oxidative stress and energy metabolism in C2C12 cells and animal models. Therefore, we suggest that TA can be a powerful substance in healthy functional foods and therapeutics to improve fatigue.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.7
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• pp.790-800
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• 2017

As men get older, total testosterone levels decline gradually, and concentrations of free and bioavailable testosterone decline sharply with each decade beyond their 30s. Andropause or testosterone deficiency syndrome (TDS) is defined as a decrease in sexual satisfaction or decline in general well-being accompanied by low levels of testosterone in older men. This male climacteric is characterized by nervousness, reduced potency, decreased libido, irritability, fatigue, depression, memory problems, sleep disturbances, and hot flushes. Cirsium japonicum (CJ) is used as a traditional medicine for hemorrhage, blood congestion, and inflammation in Korea. However, there is no report on the efficacy of CJ treatment for TDS. In this study, we observed the mitigating effect of CJ extract (CE) and fermented CJ extract (FCE) on symptoms of TDS. In elderly male rats, total and testosterone levels, hind limbs muscles, forced swimming time, and total and motile sperm counts significantly increased after daily intake of CE and FCE for 6 weeks. In contrast, sex hormone binding globulin, retroperitoneal fat, total serum cholesterol, and triglyceride levels were significantly reduced in CE and FCE groups. However, there was no difference in prostate specific antigen, aspartate aminotransferase, and alanine aminotransferase levels among all groups, which means CE and FCE did not have putative adverse effects. In a cell experiment, we also observed that CE and FCE enhanced expression of genes related to testosterone biosynthesis but reduced genes involved in testosterone conversion. On the whole, these positive effects on TDS were greater in FCE compared to CE. Thus, these results suggest the potential of FCE as a promising natural product for recovering testosterone levels and alleviating TDS.

• Journal of Life Science
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• v.26 no.9
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• pp.1063-1073
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• 2016

Male climacteric syndrome, andropause, or testosterone deficiency syndrome (TDS) is one of the new health issues in elderly men. It is a natural phenomenon that happens with age in men, which is clinically characterized by a decline in levels of serum testosterone resulting in a significantly decreasing of physical and mental activities. The aim of this study was to investigate the putative alleviative effects of dandelion extract on the symptoms of TDS by increasing serum testosterone levels and compare the efficacy between dandelion extract (DE) and fermented dandelion extract (FDE). After daily intake of DE and FDE for 4 weeks, serum testosterone levels, muscles of vastus lateralis, forced swimming time, total sperm counts, and motile sperm counts were significantly increased in older rats (22 weeks). Additionally, SHBG, epididymal fat pad, total serum cholesterol and triglyceride were significantly decreased in DE and FDE fed groups. However, PSA levels were not different among all groups. Furthermore, DE and FDE enhanced the expression of genes related to testosterone biosynthesis in TM3 Leydig cells. Overall, these positive effects on andropause were greater in FDE compared to DE. These results suggest the potential of FDE as a safe and efficacious natural material for recovering testosterone levels and reducing andropause symptoms.

• Journal of Life Science
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• v.29 no.9
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• pp.1002-1009
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• 2019

Early life stress (ELS) increases the risk of depression. ELS may be involved in the susceptibility to subsequent stress exposure during adulthood. We investigated whether epigenetic mechanisms of p11 promoter affect the vulnerability to chronic unpredictable stress (CUS) induced by the maternal separation (MS). Mice pups were separated from their dams (3 hr/day from P1-P21). When the pups reached adulthood, we applied CUS (daily for 3 weeks). The levels of hippocampal p11 expression were analyzed by quantitative real-time PCR. The levels of acetylated and methylated histone H3 at p11 promoter were measured by chromatin immunoprecipitation. Depression-like behavior was measured by the forced swimming test (FST). The MS and CUS group exhibited significant decreases in p11 mRNA level and the MS plus CUS group had a greater reduction in this level than the CUS group. The MS plus CUS group also resulted in greater reduction in H3 acetylation than the CUS group. This reduction was associated with an upregulation of histone deacetylase 5. Additionally, the MS plus CUS group showed a greater decrease in H3K4met3 level and a greater increase in H3K27 met3 level than the CUS group. Consistent with the reduction of p11 expression, the MS plus CUS group displayed longer immobility times in the FST compared to the control group. Mice exposed to MS followed by CUS had much greater epigenetic alterations in the hippocampus compared to adult mice that only experienced CUS. ELS can exacerbate the effect of stress exposure during adulthood through histone modification of p11 gene.