• Journal of Oriental Neuropsychiatry
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• v.31 no.4
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• pp.269-278
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• 2020

Objectives: Yukmijihwang-won (Liuweidihuang-wan in Chinese) is a frequently used medicinal herbal formula. It is used as Yin tonic in Korea and China to recover patients from Yin deficiency. However, the scientific evidence on this drug has not revealed the beneficial effect or mechanism of its effects on the neurological disorder. We designed this study to examine the antidepressive and analgesic effects of Yukmijihwang-won (YJ-01) and the minor modification of YJ-01, YJ-06 on the reserpine-induced pain-depression dyad mice model. Methods: Reserpine (1 mg/kg) was administered subcutaneously once a day for three consecutive days to induce pain and depression-like behavior. The oral administration of YJ-01 and YJ-06 (100, 200, or 300 mg/kg) was performed once daily from three days after the reserpine injection. Results: Repeated administration of the YJs significantly reduced the immobility time in a forced swimming test and increased the moved distance and number of crossings in the open field test. In the von-Frey filament test, the oral administration of YJs remarkably suppressed the increase in paw withdrawal frequency. Conclusions: The results of this study suggest that YJ-01 and 06 may be good candidates to treat the pain-depression dyad.

• Korean Journal of Acupuncture
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• v.38 no.2
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• pp.75-99
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• 2021

Objectives : The purpose of this study is to analyze animal behavioral changes and related neurobiological mechanisms in recent studies using animal models with pain and depression. Methods : We conducted database search in Pubmed, NDSL, and EMBASE up to January 2021. Included studies were classified as depression-like behavior observed in pain model, pain-like behavior observed in depression model, and pain and depression comorbidity model. The results of pain- and depression-like behaviors, the changes of neurobiological mechanisms, and the treatment methods such as drugs, natural substance-derived chemicals, or acupuncture were analyzed. Results : We included 124 studies (81 studies in depression-like behavior observed in pain model, 19 studies in pain-like behavior observed in depression model, and 24 studies in pain and depression comorbidity model). Pain and depression comorbidity animal models were induced using various methods by drugs or surgery. Von frey test, a method for evaluating mechanical allodynia was the most commonly used for measuring pain-like behavior and the forced swimming test was the most commonly used for measuring depression-likes behavior. The changes of neurobiological factors, such as decrease of 5-hydroxytryptamine and increase of oxidative stress and pro-inflammation cytokines were generally changed in the frontal cortex, hippocampus, thalamus, and spinal cord in all types of models. For treating pain and depression-like behaviors, various types of drugs such as antidepressant, tranquilizer, analgesic, and natural substance-derived chemicals were used. Acupuncture treatment was used in 4 studies. Conclusions : In the future, more diverse studies on the combined model of pain and depression need to be conducted. In addition, it is necessary to establish a mechanistic basis for the development of various treatments by identifying the common mechanisms of pain and depression.

• Journal of Oriental Neuropsychiatry
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• v.32 no.1
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• pp.25-37
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• 2021

Objectives: Depression is a mood disorder showing low energy, loss of interest, anhedonia, and anxiety. It affects a patients' daily life. This disease is considered a social problem because the patient may commit suicide in extreme cases. JSB is composed of 12 Korean medicinal herbs. It has been prescribed to patients with depression. The objective of this study is to investigate anti-depressive effects of JSB on restraint stress-induced depression in a mouse model. Methods: Depression was induced by restraint stress. Mice were orally administered JSB at 10, 20, or 40 mg/kg for 14 days. Forced swimming test (FST) and open field test (OFT) were performed. Brain-derived neurotrophic factor (BDNF) mRNA level was measured by real time-PCR. Plasma levels of corticosterone and serotonin were measured by ELISA. Blood levels of AST and ALS were measured using a biochemical analyzer. Results: JSB treatment significantly reduced the immobility time in FST. BDNF mRNA level was increased by JSB treatment in the hippocampi of mice. Although the expression of TNF-α was also increased by JSB, such increase was not statistically significant. The increase of corticosterone level in plasma induced by restraint stress was significantly down-regulated by JSB. JSB reduced blood level of AST, but not ALT. Conclusions: JSB has a potential to manage depression, setting a foundation for clinical application of Korean medicine with safety.

• Journal of Microbiology and Biotechnology
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• v.32 no.4
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• pp.447-457
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• 2022

Notoginsenoside R1 and ginsenoside Rg1 are the main active ingredients of Panax notoginseng, exhibiting anti-fatigue, anti-tumor, anti-inflammatory, and other activities. In a previous study, a GH39 β-xylosidase Xln-DT was responsible for the bioconversion of saponin, a natural active substance with a xylose group, with high selectivity for cleaving the outer xylose moiety of notoginsenoside R1 at the C-6 position, producing ginsenoside Rg1 with potent anti-fatigue activity. The optimal bioconversion temperature, pH, and enzyme dosage were obtained by optimizing the transformation conditions. Under optimal conditions (pH 6.0, 75℃, enzyme dosage 1.0 U/ml), 1.0 g/l of notoginsenoside R1 was converted into 0.86 g/l of ginsenoside Rg1 within 30 min, with a molar conversion rate of approximately 100%. Furthermore, the in vivo anti-fatigue activity of notoginsenoside R1 and ginsenoside Rg1 were compared using a suitable rat model. Compared with the control group, the forced swimming time to exhaustion was prolonged in mice by 17.3% in the Rg1 high group (20 mg/kg·d). Additionally, the levels of hepatic glycogen (69.9-83.3% increase) and muscle glycogen (36.9-93.6% increase) were increased. In the Rg1 group, hemoglobin levels were also distinctly increased by treatment concentrations. Our findings indicate that treatment with ginsenoside Rg1 enhances the anti-fatigue effects. In this study, we reveal a GH39 β-xylosidase displaying excellent hydrolytic activity to produce ginsenoside Rg1 in the pharmaceutical and food industries.

• The Korea Journal of Herbology
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• v.29 no.5
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• pp.9-16
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• 2014

Objectives : Investigation of the antidepressant effect of Glycyrrhizae Radix (GR) through the anti-inflammatory effect. Methods : Depression in rats was induced by LPS (i,p.3days). The rats were treated with GR100 mg/kg (GR 100) or GR400 mg/kg (GR 400). The depressive immobility was examined with Tail Suspension Test(TST) and Forced Swimming Test(FST). The expression of nuclear factor-${\kappa}B$(NF-${\kappa}B)$, $I{\kappa}B$ was measured with western blotting. The concentration of corticosterone, cytokine in plasma was measured with ELISA. The expression of c-Fos in the paraventricular nucleus(PVN) and tyrosine hydroxylase(TH) in the locus coeluleus(LC) were measured with immunostaining method. Results : In the TST, GR400 group significantly decreased immobility time compared with the LPS group. In the FST, GR100, GR400 group significantly decreased immobility time comparing with the LPS group. c-Fos expression in GR100 and GR400 group was decreased comparing with the lipoplysaccharide(LPS) group. The $I{\kappa}B$ expression of GR100 and GR400 group was increased comparing with the LPS group. The level of corticosterone of GR100 group was decreased comparing with the LPS group. The concentration of cytokine of GR100 and GR400 group was decreased comparing with the LPS group. TH expression in the LC was increased in LPS group, but in GR100 and GR400 group was not shown significant decrease. Conclusion : According to this results obtained, GR has antidepressant effects by the anti inflammatory action through the suppression of HPA axis activity, not through the action against the catecholaminergic system.

• Korean Journal of Plant Resources
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• v.35 no.4
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• pp.411-416
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• 2022

Natural products are important sources for drug development because they have a wide variety of useful biological properties. Angelica gigas Nakai (AGN) has been used as an herbal medicine for treatment of colds, pain, and anemia. The present study was designed to evaluate the regulatory effect of AGN on immune enhancement in vivo and in vitro. To investigate the immune-enhancing effect of AGN, we used forced swimming test (FST) experimental model. Mice were orally administered by AGN or distilled water for 14 days and then immobility time and biological parameters in serum were measured. The results showed that immobility time in AGN treatment group was significantly reduced in comparison with the control group. Plasma levels of blood urea nitrogen and lactate dehydrogenase in AGN group was significantly decreased compared with control group. Additionally, we showed that AGN treatment significantly increased immune-related cytokines such as interleukin (IL)-4, IL-2, and interferon (IFN)-𝛾 levels in Molt-4 cells. Collectively, the findings provide experimental evidence that AGN may be effective in improving immune function.

• Herbal Formula Science
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• v.30 no.3
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• pp.109-121
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• 2022

Objective : This study is conducted to investigate the effect of Astragali Radix on Post Traumatic Stress Disorder(PTSD) induced by the Single Proposed Stress(SPS). Methods : The experiment was conducted with five groups; SAL groups with only saline treatment, SPS group, SPS + ARX25 group, SPS + ARX50 group, and SPS + ARX100 group. After applying SPS, saline and ARX were administered for 14 days to identify the change of body weight, sucrose intake amount, and behavioral changes through Open Field Test(OFT) and Forced Swimming Test(FST). After the behavioral experiment, plasma corticosterone levels, serotonin, norepinephrine and dopamine concentrations were measured by enzyme-linked immunoassay in medical prefrontal cortex, hippocampus, and amygdala. Brain-derived neurotrophic factor(BDNF) in the hippocampus was measured using Reverse Transcription Polymerase Chain Reaction. Results : Weight change has significantly decreased in the SPS group compared to the SAL group(p<0.05). On day 14, the sucrose intake of rats has significantly increased in the SPS + ARX100 group compared to the SPS group(p<0.05). In OFT, the number of staying in the central space has significantly increased in the SPS + ARX100 group(p<0.01). In FST, immobility has significantly decreased in SPS + ARX50 group and SPS + ARX100 group(p<0.05). The concentration of serotonine, dopamine and BDNF expression has increased significantly in SPS + ARX100 group compared to SPS group(p<0.05) Conclusions : In the SPS-induced PTSD experiment, ARX increased sucrose intake and the numbers of crossing in the central zone space in OFT, decreased immobility time in FST, and increased concentration of serotonin, dopamine, and BDNF. It can be postulated that the ARX could be effective for the treatment of PTSD.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.255-264
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• 2023

Background: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice. Methods: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests. Results: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF⁺NeuN⁺ cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased. Conclusion: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.

• International Journal of Industrial Entomology and Biomaterials
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• v.46 no.2
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• pp.60-66
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• 2023

Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases and is more common in older and obese individuals. Silkworm male pupae exerts tonic effects by increasing testosterone secretion and the forced swimming time and muscle ratio increased in mice consuming silkworm pupae, which may be beneficial to the older population. Therefore, it will be beneficial to investigate the effects of silkworm pupal extracts (SPE) on OA. To confirm this effect, we prepared SPE in different solvents, and their ability to attenuate matrix metalloproteinases (MMPs) and inflammatory mediators (interleukin-6 [IL-6], interleukin-8 [IL-8] and tumor necrosis factor-α [TNF-α]) were evaluated in an interleukin-1β (IL-1β)-induced SW1353 human chondrosarcoma cell line. 70% ethanolic SPE outperformed the other solvents, reducing MMP-1 and MMP-3 expression by up to 53% and 13%, respectively. Further experiments were performed using 70% ethanolic SPE from three distinct pupation stages in males and females. SPE treatment alleviated MMP-1 expression (43.9-47.4%) regardless of pupation stage and sex. Among the inflammatory mediators, 70% ethanolic SPE alleviated IL-6 and TNF-α levels, and the concentrations thereof were lowest in the early-stage male SPE-treated group (43.15% and 56.74%, respectively). In conclusion, 70% ethanolic SPE may prevent IL-1β-induced osteoarthritis by inhibiting MMPs and inflammatory cytokines. Therefore, SPE is a potential therapeutic agent for the treatment of OA.

• Journal of the Korean Society of Food Culture
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• v.22 no.2
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• pp.261-265
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• 2007

The antidepressant effects of Cirsium japonicum was revealed in previous studies using open field test and forced swimming test. The contents of total flavonoids and apigenin of Cirsium japonicum were analyzed and sensory evaluation of Cirsium japonicum tea was performed in order to develop Cirsium japonicum tea as an antidepressant. Among the different plant parts of Cirsium japonicum, leaves had the highest level of total flavonoids and apigenin contents and were followed by flowers and stems. Drying method affected total flavonoids and apigenin content of Cirsium japonicum, but regular pattern was not revealed. In sensory evaluation, overall acceptance of Cirsium japonicum flower-leaf mix tea was higher than those of Cirsium japonicum leaf tea. Also purchase intention of Cirsium japonicum flower-leaf mix tea was higher than those of Cirsium japonicum leaf tea.