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Biomedical subjects

Hyunsu Bae

Publications and source records attributed to Hyunsu Bae.

At least 19 recordsLinked to original sources

The difference in mRNA expressions of hypothalamic CCK and CCK-A and -B receptors between responder and non-responder rats to high frequency electroacupuncture analgesia.

The present study was performed to determine whether the expression levels of the hypothalamic cholecystokinin (CCK) and its receptors are associated with the responsiveness to high frequency electroacupuncture (EA) analgesia in rats. EA stimulation (100 Hz, 0.5 ms pulse width, 0.2-0.3 mA) was delivered to the Zusanli (ST36) acupoint of male Sprague-Dawley rats for 20 min without anesthetics or holder restraint. The analgesic effect of EA was quantified using a tail flick latency test, and subsequently animals were allocated to responder or non-responder groups. The hypothalamus of rats in each group was dissected and RNA was purified. The mRNA expressions of CCK, and CCK-A and -B receptor were determined by real-time RT-PCR. CCK mRNA levels were not significantly different in the two groups, whereas both CCK-A and -B receptors were significantly more expressed in non-responders. These results suggest that the level of CCK receptor mRNA expression in the hypothalamus, rather than CCK mRNA, has an important relationship with the individual variations to high frequency EA analgesia in rats.

Analgesia↗

Effect of Acori graminei Rhizoma on contractile dysfunction of ischemic and reperfused rat heart.

Acori graminei Rhizoma is one of the best-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in Asian countries. The anti-ischemic effect of Acori graminei Rhizoma on ischemia-induced isolated rat heart was investigated through analysis of changes in perfusion pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into two groups, an ischemia-induced group without any treatment (I), and an ischemia-induced group with Acori graminei Rhizoma treatment (I+AGR). There were no significant differences in perfusion pressure, aortic flow, coronary flow, or cardiac output between the two groups before ischemia was induced. The supply of oxygen and buffer was stopped for 10 min to induce ischemia in isolated rat hearts, and Acori graminei Rhizoma was administered while inducing ischemia. The data showed that Acori graminei Rhizoma treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under an ischemic condition. In addition, hemodynamics (except heart rate) of the AGR-treated group was significantly recovered 60 min after reperfusion compared to the control group, (systolic aortic pressure: 85.5% vs. 62.5%, aortic flow volume: 68.1% vs. 49.4%, coronary flow volume: 86.8% vs. 60.1%, and cardiac output: 73.1% vs. 54.1%, p<0.01). These results suggest that Acori graminei Rhizoma has distinct anti-ischemic effects.

Animals↗

The effects of BR003 on memory and cell proliferation in the dentate gyrus of rat hippocampus.

BR003 is a multi-herbal formula that contains twelve medicinal herbs. We investigated the effects of oral administration of BR003 to Wistar rats on (a) learning and memory using a passive avoidance test and (b) cell proliferation in the dentate gyrus (DG) of the hippocampus using immunohistochemical analysis of 5-bromo-2-deoxyuridine (BrdU) expression. In the passive avoidance test, the retention time of the BR003-treated group was significantly longer than that of the control group (182.64+/-39.88 vs. 73.08+/-29.30 s, respectively; n=11; p<0.05). There were significantly more BrdU-immunoreactive cells in the DG in the BR003-treated group than in the control group (1281.07+/-151.16 vs. 818.01+/-132.98 cells per DG, respectively; n=11; p<0.05). These results suggest that the administration of BR003 not only improves learning and memory but also increases cell proliferation in the DG of the rat hippocampus.

Animals↗

Inhibition of lipopolysaccharide and interferon-gamma-induced expression of inducible nitric oxide synthase and tumor necrosis factor-alpha by Lithospermi radix in mouse peritoneal macrophages.

Lithospermi radix (LR, root of Lithospermum erythrorhizon Siebold. et Zuccarinii) has been used to treat various conditions, such as septic shock, eczema and burns. In this study, the effect of LR on lipopolysaccharide (LPS) and recombinant interferon-gamma (rIFN-gamma)-induced production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha were examined using mouse peritoneal macrophages. At 0.01-1 mg/ml, LR inhibited the LPS/rIFN-gamma-induced expression of inducible nitric oxide synthase (iNOS) and TNF-alpha release. To clarify the mechanism involved, the effect of LR on the activation of nuclear factor (NF)-kappaB was examined. The LPS/rIFN-gamma-induced activation of NF-kappaB was almost completely blocked by LR at 1mg/ml without cytotoxicity. These findings demonstrate that the inhibition of the LPS/rIFN-gamma-induced production of NO and TNF-alpha by LR involves the inhibition of NF-kappaB activation.

Animals↗

Effects of bee venom on the pro-inflammatory responses in RAW264.7 macrophage cell line.

The purpose of this study is to elucidate the molecular mechanism of anti-inflammatory effect of bee venom (BV), which has been used for the treatment of various inflammatory diseases in oriental medicine. With this aim, we examined the effects of BV on the nitric oxide (NO) production by lipopolysaccharide (LPS) or sodium nitroprusside in RAW264.7 macrophages. We further investigated the effects of BV on the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) with RT-PCR in LPS-stimulated RAW264.7 cells. BV suppressed the NO production and decreased the levels of iNOS, COX-2, NF-kappaB and MAPK mRNA in a dose-dependent manner. These results suggest that BV has an anti-inflammatory effect by inhibiting iNOS and COX-2 expression, possibly through suppression of NF-kappaB and MAPK expression.

Animals↗

Bee venom modulates murine Th1/Th2 lineage development.

Administration of bee venom (BV) elicits anti-inflammatory, anti-nociceptive and anti-allergic effects in various animal models. This study was designed to evaluate the direct effects of BV on helper T cell activities and on Th1/Th2 lineage development using both in vitro and in vivo conditions. In the Th1 skewed condition, BV increased the expression of IFN-gamma mRNA and enhanced the expression of T-bet on purified CD4(+) T cells from splenocytes of BALB/c mice. On the other hand, BV treatment did not alter the expression of IL-4 or GATA-3 in a Th2 driven environment. To elucidate the effects of BV on Th1/Th2 lineage development under in vivo conditions, BV was given by intraperitonial injection to BALB/c mice. It significantly increased the CD4(+) T cell population and enhanced IFN-gamma expression, while IL-4 transcripts were not altered upon in vivo activation using an anti-CD3 antibody injection. Taken together, these results imply that BV induces Th1 lineage development from CD4(+) T cells by increasing the expression of a Th1-specific cytokine, IFN-gamma. In addition, this result may be mediated by inducing a Th1-specific transcription factor, T-bet.

Animals↗

The multi-herbal formula Guibi-tang enhances memory and increases cell proliferation in the rat hippocampus.

Guibi-tang (GBT) is a multi-herbal medicinal formula that has been used to treat amnesia in the traditional Korean medicine system for hundreds of years. In this study, we investigated the effects of GBT on learning and memory function in Wistar rats by using the foot shock passive avoidance test. In addition, cell proliferation was examined using 5-bromo-2-deoxyuridine (BrdU) uptake and immunostaining in the dentate gyrus of the rat hippocampus after oral administration of GBT. In the passive avoidance test, the retention time of the GBT-treated group was significantly longer (almost 2.5-fold) than that of the control group. The number of BrdU-immunoreactive cells in the dentate gyrus was significantly higher in the GBT-treated group (almost twofold) than in the control group. These results suggest that administration of GBT to rats not only improves learning and memory but also increases the proliferation of cells in the dentate gyrus of the hippocampus.

Animals↗

Efficacy of a traditional Korean medicine, Chung-Sang-Bo-Ha-Tang, in a murine model of chronic asthma.

Traditional herbal medicines may be viable alternatives to corticosteroid therapy for treatment of asthma. However, the therapeutic mechanisms of herbal compounds remain a matter of considerable debate. This study was performed to evaluate the effects of Chung-Sang-Bo-Ha-Tang (CSBHT), a herbal compound administrated therapeutically to asthma patients for centuries, on airway inflammation and remodeling in a murine model of chronic asthma. BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged with aerosolized OVA for 6 weeks. During the last 2 weeks, some mice were treated daily with CSBHT by intragastric feeding. Dexamethasone (Dex)-treated, phosphate-buffered saline (PBS)-treated, and naive mice served as controls. The effects of CSBHT on airway inflammation, lung pathology, and cytokine production were evaluated. Mice exposed to recurrent airway challenge with OVA had chronic inflammation and characteristics of airway remodeling, including subepithelial fibrosis, epithelial hypertrophy, and goblet cell hyperplasia. CSBHT was as effective as Dex at moderately reducing these changes compared to the PBS-treated mice. In addition, IL-5 and IFN-gamma levels in supernatants of Concanavalin A (Con A)-activated splenocyte cultures were reduced in mice treated with CSBHT. Treatment with CSBHT during the last 2 weeks of challenge modulated airway inflammation and remodeling in a murine model of chronic asthma. Thus, CSBHT may effectively delay the progression of airway inflammation and remodeling.

Administration, Oral↗

Electroacupuncture up-regulates natural killer cell activity Identification of genes altering their expressions in electroacupuncture induced up-regulation of natural killer cell activity.

As an important cellular component of the innate immune system, NK cells constitute a first line of defense against various infections and malignancies. Previous studies have reported electroacupuncture (EA) modulation of natural killer cell (NK cell) activities. Our study confirmed that EA treatment increases NK cell activity using (51)Cr release assay. Furthermore, in order to better understand the activation mechanism of NK cell by EA, we employed a cDNA microarray technique to elucidate how EA alters gene expressions in the spleen of rats. We screened EA responsive genes using a high-throughput screening and identified 154 genes. Among those genes we selected 4 genes that are known to play a crucial role in NK cell activation and examined their mRNA expressions after EA treatment using RT-PCR. Our data shows that EA treatment increased CD94, PTK and VCAM-1 expressions while decreased PTP and SHP-1. These results imply that EA treatment increase PTK expression, which increases NK cell activity, through induction of CD94 while decreases SHP-1, which inhibits NK cell activity, simultaneously so that it activates NK cell with high efficacy. It seems that increased VCAM-1 expression is due to INF-gamma produced by activated NK cell. Increased production of VCAM-1 is expected to play an important role in binding of NK cell to the target cell. The result of our study may provide key insights in understanding the mechanisms of activation of NK cell induced by EA.

Acupuncture Points↗

Yukmijihwang-tang derivatives enhance cognitive processing in normal young adults: a double-blinded, placebo-controlled trial.

Yukmijihwang-tang (YMJ), also known as Luweidihuang-tang in China, has been widely used as a general herbal tonic for hundreds of years in many Asian countries. This study examines whether YMJ derivatives (YMJd) enhance cognitive ability in normal human subjects and discusses its potential as treatment for dementia patients with deficient cognitive ability. Subjects were divided into two groups, the placebo-treated group (n = 15) and the YMJd-treated group (n = 20). K-WAIS tests, a Korean version of an individual intelligence quotient (IQ) test, and a P300 latency assessment of event-related potential (ERP) were conducted in order to measure changes in cognitive ability before and after 6 weeks of YMJd treatment. The K-WAIS mean scores of the group treated with YMJd were significantly higher than those of the placebo group (p < 0.05), and their mean P300 latency was substantially shorter (p < 0.005). These results suggest that YMJd treatment accelerates the speed of information processing and enhances cognitive ability. YMJd treatment may help dementia patients or the elderly recover from cognition deficiencies or degeneration in clinic.

Adolescent↗

The anti-depressant effect of Nelumbinis semen on rats under chronic mild stress induced depression-like symptoms.

Nelumbinis Semen is a well-known traditional herbal medicine frequently used in treatment of depression in many Asian countries. In this study, its anti-depression effects in rats were investigated by comparing the test results of those treated with Nelumbinis Semen to those treated with other herbal anti-depressants, including Rehmanniae Radix Preparat, Corni Fructus, Lycii Fructus, Pinelliae Rhizoma and Hypericum Perforatum. In order to induce depression-like symptoms, the animals were placed under chronic mild stress in the form of overnight illumination for 2 consecutive days. They were treated with the respective herbal extract and forced swimming tests were conducted afterwards. The anti-depression effects of each extract were then evaluated based on a measured index, which consisted of struggling time, first latency and first rest duration. These test results show that Nelumbinis Semen provides greater anti-depression effects than the other herbal extracts. Specifically, only the rats treated with Nelumbinis Semen showed significant increases in struggling time (43.9%, p < 0.005, p = 0.0037) and in first latency time (90.2%, p < 0.05, p = 0.0116). However, the first rest duration for Nelumbinis Semen treated rats was not significantly different from the other rats. It appears that Nelumbinis Semen provides even greater anti-depression effects than Hypericum Perforatum (commonly referred to as St. John's Wort, perhaps the most widely used natural antidepressant today). The anti-depression effects of Nelumbinis Semen might be due to the modulation of the amount of neurotransmitters involved in depression.

Animals↗

Nelumbinis Semen reverses a decrease in hippocampal 5-HT release induced by chronic mild stress in rats.

Depression is associated with a dysfunctional serotonin system. Recently, several lines of evidence have suggested that a very important evoking factor in depression may be a serotonin deficit in the hippocampus. This study assessed the antidepression effects of Nelumbinis Semen (NS) through increasing serotonin concentrations under normal conditions and reversing a decrease in serotonin concentrations in rat hippo-campus with depression-like symptoms induced by chronic mild stress (CMS). Using an in-vivo microdialysis technique, the serotonin-enhancing effect of NS on rat hippocampus was investigated and its effects compared with those of two well-known antidepressants, Hypericum perforatum (St John's wort) and fluoxetine (Prozac). Rats were divided into five groups: saline-treated normal, without CMS; saline-treated stress control; NS-, St John's wort- and fluoxetine-treated rats under CMS for 8 weeks or no stress treatment. NS and fluoxetine significantly increased serotonin in normal conditions and reversed a CMS-induced decrease in serotonin release in the hippocampus (P<0.05 compared with normal group or control group under CMS). These results suggest that NS increases the serotonin levels normally decreased in depression, resulting in an enhancement of central serotonergic transmission and possible therapeutic action in depression. It is suggested that NS may present an antidepressant effect through enhancement of serotonin.

Animals↗

Inhibition of production of reactive oxygen species and gene expression profile by treatment of ethanol extract of Moutan Cortex Radicis in oxidative stressed PC12 cells.

Moutan Cortex Radicis (MCR) is one of the most widely used Oriental medicines. In this study, we assessed the reducing effect of ethanol extract of MCR on hydrogen peroxide-induced reactive oxygen production, the main cause of cell damage or death in PC12 cells. The viability of cells treated with 1 mg/ml of MCR was significantly restored from that of oxidative-stressed PC12 cells. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H(2)DCFDA assay. MCR at 1-0.01 mg/ml concentration inhibited ROS production in oxidative-stressed cells. To identify candidate genes responsible for the anti-oxidative effects of MCR on PC12 cells, an oligonucleotide microarray analysis was performed. The result of gene expression profiles showed that 10 genes were up-regulated and 7 were down-regulated in MCR plus hydrogen peroxide treated cells compared with hydrogen peroxide treated cells. Among them, heme oxygenase (HO) and cathechol-O-methyltransferase (COMT) are related to regulation of ROS generation and the others are known to regulate cell survival and progression. Subsequently, we performed real-time RT-PCR to quantify the ROS related gene. MCR treatment increased the expression of HO by 370% and COMT by 280% at the concentration of 1 mg/ml. These findings suggest that MCR inhibits the production of ROS and cytotoxicity by oxidative-stressed PC12 cells through over-expression of HO and COMT.

Animals↗

Effects of Yukmijihwang-tang derivatives (YMJd), a memory enhancing herbal extract, on the gene-expression profile in the rat hippocampus.

The herbal extract Yukmijihwang-tang (YMJ) has been widely used for centuries as an anti-aging herbal medicine in Asian countries. Among the various modified prescriptions of YMJ, YMJ derivatives (YMJd) were formulated to enhance memory retention. This study has three goals: 1) to quantitatively evaluate the memory-enhancing effect of YMJd using behavior tasks; 2) to use cDNA micro-array tools to identify candidate genes responsible for enhancing memory; and 3) to statistically evaluate the specific gene expression patterns using Real-time PCR. Memory retention abilities are addressed by the passive avoidance task with SD male rat. The retention time of the YMJd group was significantly delayed (ca. 100%), whereas with Ginkgo biloba and Soya lecithin treatment, this was only delayed 20% and 10%, respectively. The cDNA from the hippocampi of YMJd and rat control groups were applied to an Incyte rat GEM2 cDNA microarray. The microarray results showed that transthyretin and PEP-19 were abundantly expressed in the YMJd treated group. Importantly, PEP-19 is a neuron-specific protein that inhibits apoptotic processes. On the other hand, neuronal genes involved in neuronal death or neurodegeneration, such as pentraxin and spectrin, were abundantly expressed in the control group. The list of differentially expressed genes may provide further insight into the action and mechanism behind the memory-enhancing effect of herbal extracts of YMJd.

Animals↗

Proteome analysis of red deer antlers.

Deer antlers are the only mammalian organs capable of repeated regeneration. Although antlers are known to develop from pedicles, which arise from antlerogenic cells of cranial periosteum, their developmental process is not fully elucidated. For example, while endocrine and environmental factors influence the antler development, it is still unclear which signaling pathways are involved in the transduction of such stimuli. To study the developmental process of antlers and identify proteins functioning in their growth, we have established proteome maps of red deer (Cervus elaphus) antlers. With two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization mass spectrometry, we analyzed more than 800 protein spots and identified approximately 130 individual proteins derived from the growing tip of antlers. The overall profile of the antler proteome was dissimilar to those of other types of tissue. Also comparison of proteomes derived from proximal bony tissue and the growing tip of antlers revealed substantial differences. Moreover several cell growth or signaling-related proteins are expressed exclusively in the growing tip, suggesting that these proteins function in the growth and differentiation of antlers. Currently, using the antler proteome maps, we are actively searching for the regulatory factor(s) that may control the antler development.

Animals↗

Ginsenoside Rg1 enhances CD4(+) T-cell activities and modulates Th1/Th2 differentiation.

Panax ginseng is commonly used as a tonic medicine in Asian countries such as Korea, China, and Japan. It has been reported that ginsenoside Rg1 in P. ginseng increases the proportion of T helper (Th) cells among the total number of T cells and promotes IL-2 gene expression in murine splenocytes. This implies that ginsenoside Rg1 increases the immune activity of CD4(+) T cells, however, the exact mechanism remains unknown. The present study elucidated the direct effect of Rg1 on helper T-cell activities and on Th1/Th2 lineage development. The results demonstrated that ginsenoside Rg1 had no mitogenic effects on unstimulated CD4(+) T cells, but augmented CD4(+) T-cell proliferation upon activation with anti-CD3/anti-CD28 antibodies in a dose-dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4(+) T cells. In Th0 condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4(+) T cells, suggesting that Rg1 prefers to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secretion in CD4(+) T cells under Th2 skewed condition, while decreasing IFN-gamma secretion of cells in Th1 polarizing condition. Thus, Rg1 enhances Th2 lineage development from the naïve CD4(+) T cell both by increasing Th2 specific cytokine secretion and by repressing Th1 specific cytokine production. Therefore, these results suggest that ginsenoside Rg1 is a desirable agent for enhancing CD4(+) T-cell activity, as well as the correction of Th1-dominant pathological disorders.

Animals↗

Traditional Korean medicine (SCRT) modulate Th1/Th2 specific cytokine production in mice CD4+ T cell.

Traditional Korea medicine, So-Cheong-Ryong-Tang (SCRT) also called as Xiao-qing-long-tang or Sho-seiru-to, contains eight species of medicinal plants and has been used for treating allergic diseases, such as allergic rhinitis and asthma, for hundreds of years in Asian countries. CD4+ T cells were highly purified by using magnetic bead from splenocytes of BALB/c mice. SCRT treatment slightly decreased the expression of cell surface protein CD69 on CD4+ T cell in the flow cytometry analysis. In RT-PCR analysis, SCRT increases the expression of IL-2 and IL2R-alpha mRNA, and decreases the expression of IL-4 mRNA, which is an important cytokine of Th2 cell development. On the other hand, SCRT treatment increases IFN-gamma expression, which is one of the key cytokines for Th1 cell development. Present study implies that SCRT can correct Th2 dominant condition directly affecting to the CD4+ T cell without significantly depressing general T cell activities. These results also suggest that the effect on CD4+ T cell may be the one of key pharmacological effect point for treating IgE medicated allergic asthma by SCRT.

Adjuvants, Immunologic↗

Suppression of IgE production and modulation of Th1/Th2 cell response by electroacupuncture in DNP-KLH immunized mice.

Effects of electroacupuncture (EA) on Th1/Th2 cell response were investigated in BALB/c mice immunized intraperitoneally with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH). Successive electroacupuncture stimulation on the ST36 acupoint was performed just after immunization. Serum levels of antigen-specific IgE and total IgE were significantly decreased compared with non-acupunctured controls. Production of the Th2-specific cytokines IL-4 and IL-13 in the anti-CD3 mAb-activated splenocytes was significantly suppressed in ST36 electroacupunctured mice compared with non-acupunctured mice. These results imply that successive electroacupuncture on ST36 can decrease the serum level of antigen-specific IgE and total IgE by suppression of the Th2 lineage development.

Animals↗