• The Korea Journal of Herbology
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• v.31 no.5
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• pp.1-6
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• 2016

Objectives : Nardostachys jatamansi (NJ) is a medicinal herb that has been reported in various traditional systems of medicine for its use in antispasmodic, a digestive stimulant, skin diseases. Previous studies have already reported that NJ effectively protects against inflammation. However, the active compound in NJ is unknown. Therefore, in the present study, we analyzed effects of a compound, 8α-hydroxy pinoresinol (HP), isolated from NJ against lipopolysaccharide (LPS) induced inflammation in RAW 264.7 cells.Methods : To examine the anti-inflammatory effect of HP against LPS, intraperitoneally pre-treat the HP (100, 200, 500 and 1,000 nM) 1 h prior to LPS challenges. LPS was stimulated with 500 ng/ml in RAW 264.7 cells. To identify the anti-inflammatory effect of HP, we measured inflammatory mediators such as inducible nitric oxide synthase (iNOS) and its derivative nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2). Also we evaluated molecular mechanisms including mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-κB) activation by western blot.Results : The HP inhibited production of inflammatory mediators, such as iNOS and its derivative NO, COX-2 and PGE2 in LPS- induced inflammationin RAW 264.7 cells. Additionally, HP also inhibited activation of p38 pathway signaling but not extracellularsignal-regulatedkinase (ERK), c-jun NH2-terminal kinase (JNK), and NF-κB.Conclusion : Our results suggest that HP has anti-inflammatory functions through the dephosphorylation of p38 and HP can provide beneficial strategy for prevention and therapy of inflammation.

• Restorative Dentistry and Endodontics
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• v.26 no.5
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• pp.436-442
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• 2001

Neuropeptide such as calcitonin gene-related peptide and substance P may mediate neurogenic inflammation, but little is known about the regulation of neuropeptide release from rat spinal cord. Eugenol has been reported to reduce odontogenic pain and is known to have a structure similar to capsaicin, a potent stimulant of certain nociceptors. This study was done to examine the effect of capsaicin and eugenol on immunoreactive calcitonin gene-related peptide (iCGRP) release from rat spinal cord and whether eugenol regulates capsaicin-sensitive release of iCCRP or it evokes capsaicin-sensitive release of iCGRP. The dor-sal half of rat lumbar spinal cord was chopped into 200$\mu$m slices. They were superfused (500$\mu$l/min) in vitro with an oxygenated Kreb's buffer. The EC$_{50}$ of capsaicin on iCGRP release was measured. Eugenol (600$\mu$M and 1.2mM) and vehicle (0.02% 2-hydroxyl-$\beta$-cyclodextrin) were administered prior to stimulation of rat lumbar spinal cord with capsaicin. The amount of iCGRP release from rat lumbar spinal cord was measured by radioimmunoassay. The results were as follows : 1. iCGRP release from rat lumbar spinal cord was dependent on concentration of capsaicin. The EC$_{50}$ of capsaicin on iCGRP release was 3$\mu$M. 2. In the vehicle treated group, capsaicin (3$\mu$M) evoked a 14-fold increase over basal iCGRP level. 3. Administration of 600$\mu$M and 1.2mM eugenol evoked a 2.2-fold increase and a 2.3-fold increase over basal iCGRP level respectively. 4. Administration of 600$\mu$M and 1.2mM eugenol increased capsaicin evoked release of iCGRP by more than 50%. These results indicate that eugenol evoke CGRP release from central nervous system and potentiate the pain-inducing action of capsaicin on it.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.321-329
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• 2006

Albuterol, a selective ${\beta}_2$-adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of albuterol sulfate was investigated in hairless mouse skin in vitro with and without pretreatment with enhancers. The enhancing effects of ethanol and various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, and fatty acids on the permeation of albuterol sulfate were evaluated using Franz diffusion cells. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increased the permeability of albuterol sulfate approximately 33-fold compared with the control without enhancer pretrement, followed by d-limonene with enhancement ratio of 21.79. 2-Pyrrolidone-5-carboxylic acid increased the permeability of albuterol sulfate approximately 5.5-fold compared with the control. Other pyrrolidones tested showed only slight permeability enhancing effect with enhancement ratio less than 2.8. Nonionic surfactants showed moderate enhancing effects. Lauric acid increased the permeability of albuterol sulfate approximately 30-fold with decreasing the lag time from 2.85 to 0.64 hr. Oleic acid and linoleic acid showed enhancement ratio of 24.55 and 22.91, respectively. These findings would allow a more rational approach for designing formulations for the transdermal delivery of albuterol sulfate and similar drugs.

• Journal of Chest Surgery
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• v.25 no.4
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• pp.364-382
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• 1992

In order to investigate the effect of intracellular cyclic GMP on the calcium channel, whole cell patch clamp technique with internal perfusion method was used in the single ventricular myocytes of the rabbit. Cyclic GMP, cGMP analogues, cAMP, isopernaline and forskolin were perfused into cells and their effects on the calcium current were analysed by applying depolarizing step pulse of 10 mV in amplitude for 200 msec from holding potential of -40 mV. Calcium currents usually activated from -30 mV and then reached a peak at +10 mV. Amplitude of the calcium current was standardized with membrane capacitance, 50 pF. Peak amplitude at +10 mV in control was -0.15 nA/50pF. When 100 mM cAMP was applied from the pipette, peak amplitude of calcium current increased to -0.32 nA and addition of 1 mM isoprenaline further increased its amplitude. In the presence of cGMP it alone also produced an increase of the calcium current to -0.52 nA/50pF and addition of isoprenaline or forskolin increased its magnitude to -[0.55~0.95] nA/50pF. Simultaneous application of cGMP and cAMP increased the calcium current to -0.67 nA/50pF. Among the cGMP analogues, 8-Br-cGMP was the most potent stimulant for the calcium current activation. From the above results it could be concluded tlat cGMP increases the calcium current not through cAMP dependent protein kinase nor cAMP dependent phosphodiesterase pathway, but through independent phosphorylation pathway, possibly cGMP dependent protein kinase pathway.

• Journal of Applied Biological Chemistry
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• v.59 no.1
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• pp.37-43
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• 2016

Bioactive components of ultra-fine ground Saururus, the extraction yield increases when the leaves are ultra-fine ground. Comparison of normal-ground and ultra-fine ground Saururus chinensis leaves showed that the solid content and antiinflammatory activity of ultra-fine ground extracts was higher than that of normal-ground extracts. Lipopolysaccharide (LPS)-stimulated Raw 264.7 cells were treated with different concentrations of Saururus chinensis extract and the amount of nitric oxide (NO) was determined; LPS-treated cells produced 2 times more NO than cells that were not treated with LPS. Moreover, the NO production in cells treated with Saururus chinensis extract was inhibited in a concentration-dependent manner. Because the stimulant-induced NO production is regulated by the inducible nitric oxide synthase (iNOS), we measured the iNOS protein level to elucidate the mechanism by which the NO production was inhibited. We found that the amount of iNOS decreased dose-dependently. It was reduced by 53% at a Saururus chinensis extract concentration of $100{\mu}g/mL$. The protein expression of cyclooxygenase-2 (COX-2) in LPS-treated Raw 264.7 cells was inhibited by 31% at $100{\mu}g/mL$ of Saururus chinensis extract. Gel shift of the nuclear factor kappa B-DNA complex occurred in LPS-treated cells and the intensity of the band decreased gradually in a concentration-dependent manner. Ultra-fine ground Saururus chinensis extract had a concentration-dependent inhibitory effect on the production of prostaglandin $E_2$, tumor necrosis factor ${\alpha}$, interleukin $1{\beta}$ (IL-$1{\beta}$), IL-6, and IL-8 in LPS-treated Raw 264.7 cells, i.e., at $50{\mu}g/mL$ of Saururus chinensis extract, their levels were decreased by 53, 67, 52, 37, and 21% respectively.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.683-688
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• 2003

Caffeine (1,3,7-trimethylxanthine), a central nervous system stimulant, is contained in various foods, beverages and over-the-counter medications. Sulfadimethoxine (SDM) is one of the anti-thyroid agents and induces proliferation of thyroid capsule in two stage thyroid carcinogenesis model using N-bis(2-hydroxypropyl)nitrosamine (DHPN). In this study, we examined the effect of caffeine on fibrous proliferation of thyroid capsule in DHPN and SDM-treated rats. Five-week-old male F344 rats were given a single subcutaneous injection of DHPN (2,800 mg/kg, body weight). Starting one week thereafter, SDM (1,000 ppm in drinking water) with or without caffeine (1,500 ppm in diet) was administered for 12 weeks. All animals were autopsied and histopathological examination of the thyroid glands was performed. Thyroid follicular proliferative changes were induced in all rats treated with DHPN+SDM. In addition, the proliferation of perithyroidal fibrous tissue and pleomorphic thyroid follicular cells within the capsule were observed in DHPN+SDM treated group. Caffeine would not be related to these lesions in this experimental condition. although pentoxifylline, a methyl xanthine derivative, has an anti fibrotic effects.

• Korean Journal of Pharmacognosy
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• v.2 no.1
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• pp.23-28
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• 1971

This study was planned to see whether the Panax Ginseng root has any influence upon the emotionality in rats exposed to a novel open-field and induced by a grid shock. Sixty four male albino rats whose body weight ranged from 130 to 180 gm were used. They were divided into four groups, i.e., placebo control group, 5mg/kg Ginseng ext. group, 10mg/kg Ginseng ext. group, and 20mg/kg Ginseng ext. group. Sixteen rats were subjected in each group. Open-field activity was measured in a $2.20m\;{\times}\;2.20m$ open-field that was divided into 15cm squares. Four novel objects and food pellets were put with an equal distance in the open-field. Locomotion was recorded by entering the number of squares traversed for 4 min. and behaviors which were shown at the 10-sec. period were checked by a modified Jarrad and Bunnel's observation procedure. Sensitivity to the grid shock was measured in a compartment of shuttle box. 10, 20, 30, 40, 50, 60 and 70 volt ac. 2 sec., electric shock were delivered in each subject by the grid to animal's feet. Flinch, vocalization and jumping responses were rated in each shock level. The results obtained were as follows: 1.) 5mg/kg and 10mg/kg Ginseng ext. groups were tended to increase the ambulation and exploration compared with placebo control. 2.) All Ginseng extract groups were defecated significantly less often than placebo control in the open-field and shock situation. 3.) Thresholds to the electric shock were tended to elevate in all Ginseng groups. 4.) These results suggest that Ginseng extract has a stimulant action in open-field and a tranqulizing action in feared situation.

• Journal of Pharmaceutical Investigation
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• v.29 no.4
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• pp.329-335
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• 1999

Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic bronchitis and pulmonary emphysema. For the purpose of developing a transdermal preparation for clenbuterol, we attempted to select an optimal solvent system and permeation enhancer among fatty acids and fatty alcohols which are known to accelerate the penetration of various drugs in permeation experiments using hairless mouse skin and Franz diffusion cell. Apparent partition coefficient of clenbuterol was increased as pH of buffer solution was increased and solubility of clenbuterol was increased as the percent of propylene glycol(PG) in buffer solution(pH 10) was increased. Permeability of clenbuterol from different buffer(pH 10)/PG solvent mixtures was decreased as the percent of PG in pH 10 buffer solution was increased and among the various enhancers studied, lauryl alcohol was found to be the most effective enhancer, increasing the permeability of clenbuterol approximately 76-fold compared with control. Lauryl alcohol$(0{\sim}2%)$ enhanced the permeability of clenbuterol concentration-dependently. In this study, the optimal solvent system for the penetration of clenbuterol was found to be 50/50 buffer(pH 10)/PG solvent mixture containing 2% lauryl alcohol.

• Journal of Cancer Prevention
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• v.21 no.3
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• pp.144-151
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• 2016

Background: Immunoregulatory elements have emerged as useful immunotherapeutic agents against cancer. In traditional medicine, Mori folium, the leaf of Morus alba L. (Moraceae), has been used for various medicinal purposes; however, the immunomodulatory effects have not been fully identified. We evaluated the immunoenhancing potential of water extract of Mori folium (WEMF) in murine RAW264.7 macrophages. Methods: RAW264.7 cells were treated with WEMF for 24 hours and cell viability was detected by an MTT method. Nitric oxide (NO) levels in the culture supernatants were assayed using Griess reagent. The productions of prostaglandin $E_2$ ($PGE_2$) and immune-related cytokines was measured using ELISA detection kits. The mRNA and protein expression levels of Inducible NO synthase, COX-2, and cytokines were assayed by reverse transcription-PCR and Western blotting, respectively. The effect of WEMF on phagocytic activity was measured using a Phagocytosis Assay Kit. Results: WEMF significantly stimulated the production of NO and $PGE_2$ as immune response parameters at noncytotoxic concentrations, which was associated with the increased expression of inducible NO synthase and COX-2. The release and expression of cytokines, such as $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-6, and IL-10, were also significantly increased in response to treatment with WEMF. Moreover, WEMF promoted the macrophagic differentiation of RAW264.7 cells and the resulting phagocytosis activity. Conclusions: WEMF has the potential to modulate the immune function by regulating immunological parameters. Further studies are needed to identify the active compounds and to support the use of WEMF as an immune stimulant.

• Food Science and Preservation
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• v.6 no.4
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• pp.506-513
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• 1999

The growth of lactic acid bacteria was investigated in liquid broth medium containing organic germanium compound(Ge-132, carboxyethylgermanium sesquioxide) in the range of 0.01 to 10mg/ml. Most of all lactic acid bacteria tested were tolerant and could grow better to the high Ge-132 concentration. However, the growth of Leuconostoc mesenteroides and Pediococcus pentosaceus were inhibited in the presence of 10mg/m1 Ge-132. Among 22 strains tested, lactic acid bacteria that were grown to a high degree(about 2 times) by addition of Ge-132 (10mg/ml)were Lactococcus lactis, Lc. cremoris, Lc. diacetilactis, Enterococcus faecium and Streptococcus faecalis. The growth of these strains were markedly accelerated in the culture medium supplemented with 1.omg/ml Ge-132 The optimal concentration of glucose for growth of Lc. lactic was found to be high in medium containing Ge-132 as compared with the case of control. During cultivation viscosity in culture broths of Lc. lactis and Lc. cremoris was rapidly elevated by adding Ge-132 to medium containing high concentration of glucose, and then decreased after incubation of long time. However, in the cultivation of Lc. diacetilactis, E, faecium and S. faecalis, viscosity of culture broths was not increased, even though Ge-132 was shown to be an effective stimulant of growth.