• The Korea Journal of Herbology
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• v.23 no.4
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• pp.9-19
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• 2008

Objectives: In this study the authors investigated effects of the ethanolic extract of Rhodjola Rosea(HKC) on fatigue and hypothalamic IEG expression in rat forced swimming(FS) model. Methods: Sprague-Dawley rats were administered HKC extract(25 mg/100g, p.o.) for 3 days prior to FS, some rats underwent 10 min FS and others exhaustive forced swimming(EFS). In addition, other rats were administered extract at different times after EFS over 3 consecutive days. Results: When HKC administered before 10 mins of FS, serum actate dehydrogenase(LDH) and creatine phosphokinase(CPK) activities were significantly lower than control group. When HKC administered prior to EFS, blood lactate was significantly lower versus control group. When HKC was administered after EFS, blood lactate(at 6 and 24 hours after EFS) were significantly lower and serum LDH, CPK activities(at 24 hours after EFS) were significantly lower versus control group. When HKC was administered after EFS, c-Fos positive neurons in hypothalamic periventricular area(PVA), medial part(mPVN) and anterior hypothalamic nucleus caudal part(AHC) were significantly lower at 24 hours after EFS than in control group. HSP-72 positive neuron numbers in hypothalamus were significantly lower at 24 hours after EFS than in control group. Finally, when HKC was administered prior to 10 mins FS, HIF-$1{\alpha}$ expression in the gastrocnemius muscle was significantly increased. Conclusions: These results suggest that HKC extract has an anti-fatigue effect, and it reduces neuronal cell stress responses induced by physical stress by having a beneficial effect on lactate metabolism.

• The Korea Journal of Herbology
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• v.30 no.3
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• pp.69-76
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• 2015

Objectives : The effect of mixture extracted from Bupleuri Radix and Physalidis Herba(BR+RH) on the LPS-induced Depression in rats was investigated. Methods : Rats were administered intragastrically BR+PH after injectio of LPS to induce deprssion. Immobility was examined using Tail Suspension Test(TST), Forced Swimming Test(FST). The level of plasma corticosterone was measured by an Enzyme-Linked Immunosorbent Assay(ELISA) method. The expressions of c-Fos, Corticotropin Releasing Factor(CRF), NADPH-d in the Paraventricular nucleus(PVN) and TH in the Locus coeruleus(LC) were measured by immunohistochemical method. Results : In the effect of BR + PH on TST, immobility was significantly decreased comparing with the LPS group. In FST, immobility was shown decrease tendency in the BR+PH group. The expression of c-Fos in the PVN was significantly decreased at BR + PH400 group, comparing with the LPS group. The expression of CRF in PVN was shown dto have the decrease tendency in the BR+PH group, comparing with the LPS group. The expression of NADPH-d in PVN was not significantly decreased at BR+PH groups, comparing with the LPS group. The expression of TH in the LC was shown to have the decrease tendency at BR + RH groups, but not significantly, comparing with the LPS group. Conclusions : Anti-depressant effect of mixture after extracted from Bupleuri Radix and Physalidis Herba was through the anti-inflammatory effect via inhibition of HPA axis. NO and catecholamine system is not involved.

• Journal of Society of Preventive Korean Medicine
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• v.13 no.1
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• pp.13-27
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• 2009

This study aimed to validate neuroprotective effect of Chungpaesagan-tang on the early stage of cerebral ischemic damage. Cerebral ischemic damage was induced by the middle cerebral artery occlusion (MCAO) for 2 hours in the Sprague-Dawley rats. Water extract of Chungpaesagan-tang(8.7g/kg) was administered orally twice at 1 and 4 hours after the MCAO. Neurological score was tested at 3 and 24 hours after the MCAO and Chungpaesagan-tang administration. At 24 hours after the MCAO, infarct volume and edema ratio was evaluated with the TTC staining. Apoptotic cell death in cerebral cortex and caudate putamen was observed with cresyl violet staining and TUNEL labeling. Bax expression in the MCAO rat brain was stained with immunohistochemistry. Chungpaesagan-tang improved neurological and behavioral impairment of the MCAO rats and reduced infarct area, infarct volume and brain edema formation. Chungpaesagan-tang attenuated cell death percentage in cortex penumbra and reduced TUNEL positive cells in cortex penumbra and in caudate putamen of the MCAO rats. Chungpaesagan-tang reduced Bax positive neurons in caudate putamen and reduced c-Fos positive neurons in cortex penumbra of the MCAO rats. Chungpaesagan-tang intensified neuronal HSP72 expression in cortex penumbra of the MCAO rats. In results, Chunpaesagan-tang reduces infarct volume and edema formation through anti-apoptotic effect. This result suggests that Chunapaesagan-tang has an adequate neuroprotective effect on the early stage of cerebral ischemic damage.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.101-123
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• 2011

Objectives : The aim was to study the effect of bee venom pharmacopuncture therapy with different concentration on rheumatoid arthritis rat model. Methods : We enforced a bee venom pharmacopuncture therapy with different concentration on rheumatoid arthritis rat model by the intradermal injection of chicken type II collagen emulsified. 14 days after the onset of the rheumatoid arthritis rat model, a fixed volume of bee venom was daily injected to ST-35 acupoint in the rat's knee joint for 2-3 weeks. The hind paw volume, arthritic index, arthritic flexion pain test, pain threshold, and serum analysis (CRP, $PGE_2$, ALT, AST) were analyzed, and the expression profiles of COX-2, c-fos, and substance-P at the dorsal horn region of the spinal cord and subchondral bone of the knee joint were also analyzed by using the immunohistochemistry. Results : After the treatment of rheumatoid arthritis rats with bee venom pharmacopuncture, the paw volume of edema of arthritic rats were almost restored to the level of normal group, and behavior tests were very effective. Also the evaluation on the blood serum analysis was remarkable. COX-2, c-fos, and substance-P positive cells in the immunohistological section of dorsal horn region of the spinal cord and subchondral bone of the knee joints were significantly decreased. also the bee venom pharmacopuncture was effective to alleviate their rheumatoid arthritic inflammation cytokine inhibition as regards to the behavior tests and joint histological appearance. Conclusions : Based on the results in this study, bee venom pharmacopuncture with concentrated treatment condition was very effective in low fixed quantity and progressive low increased quantity.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.5
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• pp.337-341
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• 2009

Signal transducer and activator of transcription 4 (STAT4), a STAT family member, mediates interleukin 12 (IL12) signal transduction. IL12 is known to be related to calorie-restricted status. In the central nervous system, IL12 also enhances the production of nitric oxide (NO), which regulates food intake. In this study, the expression of neuronal NO synthase (Nos1), which is also related to food intake, was investigated in the hypothalamic areas of Stat4 knockout (KO) mice using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry, a marker for neurons expressing Nos1 enzyme. Western blots were also performed to evaluate Nos1 and Fos expression. Wild-type Balb/c (WT group, n=10 male) and Stat4 KO mice (Stat4 KO group, n=8 male) were used. The body weight and daily food intake in the WT group were $22.4{\pm}0.3$ and 4.4 g per day, while those in the Stat4 KO group were $18.7{\pm}0.4$ and 1.8 g per day, respectively. Stat4 mice had lower body weight and food intake than Balb/c mice. Optical intensities of NADPH-d-positive neurons in the paraventricular nucleus (PVN) and lateral hypothalamic area (LHA) of the Stat4 KO group were significantly higher than those of the WT group. Western blotting analysis revealed that the hypothalamic Nos1 and Fos expression of the Stat4 KO group was up-regulated, compared to that in the WT group. These results suggest that Stat4 may be related to the regulation of food intake and expression of Nosl in the hypothalamus.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.476-484
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• 2018

Background: Korean Red Ginseng (steamed and dried white ginseng, Panax ginseng Meyer) is well known for enhancing vital energy and immune capacity and for inhibiting cancer cell growth. Some clinical studies also demonstrated a therapeutic potential of ginseng extract for treating lung inflammatory disorders. This study was conducted to establish the therapeutic potential of ginseng saponins on the lung inflammatory response. Methods: From Korean Red Ginseng, 11 ginsenosides (Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rg3, and Rh2) were isolated. Their inhibitory potential and action mechanism were evaluated using a mouse model of lung inflammation, acute lung injury induced by intranasal lipopolysaccharide administration. Their anti-inflammatory activities were also examined in lung epithelial cell line (A549) and alveolar macrophage (MH-S). Results: All ginsenosides orally administered at 20 mg/kg showed 11.5-51.6% reduction of total cell numbers in bronchoalveolar lavage fluid (BALF). Among the ginsenosides, Rc, Re, Rg1, and Rh2 exhibited significant inhibitory action by reducing total cell numbers in the BALF by 34.1-51.6% (n = 5). Particularly, Re showed strong and comparable inhibitory potency with that of dexamethasone, as judged by the number of infiltrated cells and histological observations. Re treatment clearly inhibited the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and the c-Fos component in the lung tissue (n = 3). Conclusion: Certain ginsenosides inhibit lung inflammatory responses by interrupting these signaling molecules and they are potential therapeutics for inflammatory lung diseases.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.58-63
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• 2003

Ginseng has been recommended to alleviate the menopausal symptoms, which indicates that components of ginseng very likely contain estrogenic activity. We have examined the possibility that a component of Panax ginseng, $ginsenoside-R_{b1}$ acts by binding to estrogen receptor. We have investigated the estrogenic activity of $ginsenoside-R_{b1}$ in a transient transfection system using estrogen-responsive luciferase plasmids in MCF-7 cells. $ginsenoside-R_{b1}$ activated the transcription of the estrogen-responsive luciferase reporter gene in MCF-7 breast cancer cells at a concentration of 50 $\mu$M. Activation was inhibited by the specific estrogen receptor antagonist ICI 182,780, indicating that the estrogenic effect of $ginsenoside-R_{b1}$ is estrogen receptor dependent. Next, we evaluated the ability of $ginsenoside-R_{b1}$ to induce the estrogen-responsive gene c-fos by semi-quantitative RT-PCR assays and Western analyses. $ginsenoside-R_{b1}$ increased c-fos both at mRNA and protein levels. However, $ginsenoside-R_{b1}$ failed to activate the glucocorticoid receptor, the retinoic acid receptor, or the androgen receptor in CV-1 cells transiently transfected with the corresponding steroid hormone receptors and hormone responsive reporter plasmids. These data support our hypothesis that $ginsenoside-R_{b1}$ acts a weak phytoestrogen, presumably by binding and activating the estrogen receptor.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.506-510
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• 2012

Bone homeostasis is regulated by the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoporosis, rheumatoid arthritis and periodontal disease are related with up-regulated osteoclast formation and its activity. Gol-Swae-Bo(Drynariae Rhizoma) is widely used on skeletal disease. In this study, we sought to examine the effect of Drynariae Rhizoma in RANKL-induced osteoclast differentiation. The extract of Drynariae Rhizoma inhibited RANKL-induced osteoclast differentiation in a dose dependent manner without cytotoxicity. receptor activator of nuclear factor-${\kappa}B$ ligand(RANKL) mediated $I{\kappa}B$ degradation in bone marrow macrophages(BMMs). However, the extract of Drynariae Rhizoma inhibited RANKL induced $I{\kappa}B$ degradation in BMMs. And mRNA expression of OSCAR, TRAP, c-Fos and NFATc1 was suppressed by the extract of Drynariae Rhizoma. Moreover, the extract of Drynariae Rhizoma inhibited the protein expression of NFATc1 and c-Fos induced by RANKL. After all the analysis, these results suggest that Drynariae Rhizoma may be good candidate of medicine in the treatment of bone-related disease.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.349-355
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• 2015

We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.

• The Journal of Korean Obstetrics and Gynecology
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• v.25 no.2
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• pp.1-11
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• 2012

Objectives: This study was conducted to evaluate the inhibitory effect of Melia Fructus extract on osteoclast differentiation. Methods: MTT-assay was performed to estimate cytotoxicity of Melia Fructus extract in BMMs stimulated with M-CSF. TRAP staining, TRAP activity and Real-time PCR were performed to know the inhibitory effect on osteoclast differentiation. Actin ring formation were analysed to observe the effect of Melia Fructus extract. Results: Melia Fructus extract decreased the number of TRAP positive cells and the expression of NFATc1 gene, c-Fos gene, TRAP and OSCAR in BMMs stimulated with RANKL. Melia Fructus extract has no cytotoxicity at the concentration used in this study. Melia Fructus extract restrained the formation of actin ring. Melia Fructus inhibited NF-${\kappa}B$ activity by inducing degradation of p-$IkB{\alpha}$. Conclusions: Melia Fructus has the inhibitory effect of osteocalst differentiation and bone resorption. Further studies are needed to treat osteoporosis by herbal medicine containing Melia Fructus.