• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.16 no.3
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• pp.96-115
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• 2003

Introduction and Objectives : Administrating the Sopungchengyoungtanggami-bang (SCG) extract on to the atopic dermatitis(AD) is to study change of external dermal formation, change of leukocytes in vasculature, change of lipid formation in stratum corneum and distribution of ceramide and this study is done through forcing injury to rat's back skin which are lipid protect formation in stratum corneum. Materials and Methods : The AD which caused intentionally using the external application on the rat's back skin was used the SCG. The change of leukocytes in vasculature has been identified through optima 5.2 and student t-test and the results were made into dermal formation graph. Results : After dispensing SCG extract into the AD, the dermal injury was decreased. Especially, recover of lipid protection formation which include lipid and ceramide in stratum corneum is suppressing acute inflammation that some factors are PKC, TNF-${\alpha}$, IL-12B which controled the secretion of relating inflammatory cytokine, also went onto decrease of angiogenesis, and the decrease of degranulated mast cell. In addition, the decrease of epithelial injury also caused the growth of cell to decrease in stratum basale and cytoclasis. In the vasculature, the leukocytes were also decreased and it could relate to decrease AD Conclusions : Thus, SCG has effect on AD suppressing the dermal injury through recovering of lipid protection formation in stratum corneum.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.16 no.1
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• pp.112-129
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• 2003

Introduction and Objectives : Applying the saingheylyunbooemgami(SY) extract on to the atopic dermatitis(AD) is to study change of external dermal formation, change of leukocytes in vasculature, change of lipid formation in stratum corneum and distribution of ceramide and this study is done through forcing injury to rat's back skin which are lipid protect formation in stratum corneum. Materials and Methods : The AD which caused intentionally using the external application on the rat's back skin was used the SY. The change of leukocytes in vasculature has been identified through optima 5.2 and student t-test and the results were made into dermal foramtion graph. Results : After dispensing SY extract into the AD, the dermal injury was decreased, Especially, recover of lipid protection formation which include lipid and ceramide in stratum corneum is suppressing acute inflammation that some factors are PKC, TNF-${\alpha}$, lL-12B which controled the secretion of relating inflammatory cytokine, also went onto decrease of angiogenesis, and the decrese of degranulated mast cell. In addition, the decrease of epithelial injury also caused the growth of cell to decrease in stratum basale and cytoclasis. In the vasculature. the leukocytes were also decreased and it could relate to decrease AD. Conclusions : Thus. SY has effect on AD suppressing the dermal injury through recovering of lipid protection formation in stratum corneum.

• Journal of Microbiology and Biotechnology
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• v.17 no.10
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• pp.1712-1716
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• 2007

To generate new scaffold candidates as highly selective and potent cyelin-dependent kinase (CDK) inhibitors, structure-based drug screening was performed utilizing 3D pharmacophore conformations of known potent inhibitors. As a result, CR229 (6-bromo-2,3,4,9-tetrahydro-carbolin-1-one) was generated as the hit-compound. A computational docking study using the X-ray crystallographic structure of CDK2 in complex with CR229 was evaluated. This predicted binding mode study of CR229 with CDK2 demonstrated that CR229 interacted effectively with the Leu83 and Glu81 residues in the ATP-binding pocket of CDK2 for the possible hydrogen bond formation. Furthermore, biochemical studies on inhibitory effects of CR229 on various kinases in the human cervical cancer HeLa cells demonstrated that CR229 was a potent inhibitor of CDK2 ($IC_{50}:\;3\;{\mu}M$), CDKI ($IC_{50}:\;4.9\;{\mu}M$), and CDK4 ($IC_{50}:\;3\;{\mu}M$), yet had much less inhibitory effect ($IC_{50}:>20\;{\mu}M$) on other kinases, such as casein kinase 2-${\alpha}1$ (CK2-${\alpha}1$), protein kinase A (PKA), and protein kinase C (PKC). Accordingly, these data demonstrate that CR229 is a potent CDK inhibitor with anticancer efficacy.

• The Journal of Korean Physical Therapy
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• v.21 no.2
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• pp.109-116
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• 2009

Purpose: $17\beta$-estradiol is the most active endogenous estrogen, which is related to favorable changes in the plasma lipid profile, to relaxation of the coronary vessels, and to a decrease in platelet aggregation and vascular smooth muscle cell migration. However, although the beneficial effect of estrogens on plasma lipoproteins (ie, lowering low-density lipoprotein and increasing high-density lipoprotein cholesterol) contributes to cardiovascular protection, it does not fully account for the protective effect, particularly in the application of physical therapy, including low frequency electrical stimulation. Methods: The aim of this study was to demonstrate the inhibition of stressors, such as endothelin-1 (ET-1), serotonin (5-hydroxytryptamine, 5-HT), prostaglandin $F2\alpha$ ($PGF2\alpha$), and a protein kinase C (PKC) activator 12-deoxyphorbol 13-isobutyrate (DPB), induced isometric tension by $17\beta$-estradiol in vascular smooth muscle strips, respectively. In addition, the effects of low frequency electrical stimulation at the meridian points (CV-3, -4, Ki-12, SP-6, LR-3, BL-25, -28, -32, -52) on the indirect antihypertensive effect were examined by monitoring the changes in the serum $17\beta$-estradiol concentration in healthy volunteers. Results: Isometric tension analysis showed that the responses of inhibited tension by $17\beta$-estradiol were similar to the same stressors in rat aortic smooth muscle strips. Furthermore, although the continued amplitude modulation (AM) type of electrical stimulation was not increased significantly by electrical stimulation, the current of the frequency modulation (FM) type of low frequency electrical stimulation increased the serum $17\beta$-estradiol concentration in normal volunteers. Conclusion: These results, in part, suggest that $17\beta$-estradiol has the capacity to supress stressor-induced muscle tension, and electrical stimulation, particularly current of the FM type, has a modulatory effect on the sex steroid hormones, particularly $17\beta$-estradiol, in healthy volunteers.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.43-49
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• 2012

Stimulation of mast cells through the high affinity IgE receptor (Fc${\varepsilon}$RI) induces degranulation, lipid mediator release, and cytokine secretion leading to allergic reactions. Although various signaling pathways have been characterized to be involved in the Fc${\varepsilon}$RI-mediated responses, little is known about the precious mechanism for the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in mast cells. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-${\alpha}$ in rat basophilic leukemia (RBL-2H3) cells. IgE or specific antigen stimulation of RBL-2H3 cells increases the expression of TNF-${\alpha}$ and activates various signaling molecules including S6K1, Akt and p38 MAPK. Rapamycin specifically inhibits antigeninduced TNF-${\alpha}$ mRNA level, while other kinase inhibitors have no effect on TNF-${\alpha}$ mRNA level. These data indicate that mTOR signaling pathway is the main regulation mechanism for antigen-induced TNF-${\alpha}$ expression. TNF-${\alpha}$ mRNA stability analysis using reporter construct containing TNF-${\alpha}$ adenylate/uridylate-rich elements (AREs) shows that rapamycin destabilizes TNF-${\alpha}$ mRNA via regulating the AU-rich element of TNF-${\alpha}$ mRNA. The antigen-induced activation of S6K1 is inhibited by specific kinase inhibitors including mTOR, PI3K, PKC and $Ca^{2+}$chelator inhibitor, while TNF-${\alpha}$ mRNA level is reduced only by rapamycin treatment. These data suggest that the effects of rapamycin on the expression of TNF-${\alpha}$ mRNA are not mediated by S6K1 but regulated by mTOR. Taken together, our results reveal that mTOR signaling pathway is a novel regulation mechanism for antigen-induced TNF-${\alpha}$ expression in RBL-2H3 cells.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.166-178
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• 2003

Objectives : Nitric oxide (NO) plays an important role in normal and pathophysiological cells as a messenger molecule, neurotransmitter, microbiological agent, or dilator of blood vessels and arteriosclerosis, respectively. This study was undertaken to understand the mechanism of NO production and effect of Hyeolbuchukeo-tang (Xiefuzhuyu-tang) on NO production in cultured vascular smooth muscle cell (VSMC). Methods and Results : VSMC was isolated from aorta and cultured. Cultured primary cells were identified as VSMC with anti--smooth muscle actin antibody. A large amount of NO was produced in cultured VSMC treated with $IFN-{\gamma}$ plus TNF in a time- and dose-dependent manner. $TNF-{\alpha}$ was a more efficient stimulator than $IFN-{\gamma}$ in NO production of cultured VSMC. iNOS protein wasdetected within 3 hrs and it increased up to 12 hrs in a time-dependent manner. However, accumulated NO in cytokine-treated VSMC was not detected within 3 hrs. NO production in cytokine-treated VSMC showed the dose- and time-dependent manner, and increased up to 48 hrs. The activated VSMC produced a large amount of NO (about 60 uM). Hyeolbuchukeo-tang (Xiefuzhuyu-tang) alone did not induceNO production, but it potentiated the effect of $TNF-{\alpha}$ on NO production and increased NO production by about 20%. Hyeolbuchukeo-tang (Xiefuzhuyu-tang) did not affect the transcriptional activity of iNOS gene, but increased the accumulation of iNOS. These results indicate that Hyeolbuchukeo-tang (Xiefuzhuyu-tang) could modulate the translational level of iNOS. PKC did not modulate NO production, but calcium ionophore A23187 decreased NO production. However, Hyeolbuchukeo-tang (Xiefuzhuyu-tang) elevated the decreased NO production in A23187-treated VSMC by modulating the stability of iNOS transcripts. Half-life of the synthesized transcripts appeared to have about 6 hrs. PDTC, an $NF-{\kappa}B$ inhibitor, blocked the accumulation of iNOS mRNA, indicating that $NF-{\kappa}B$ served as an important modulator in the transcriptional regulation of iNOS. As Hyeolbuchukeo-tang (Xiefuzhuyu-tang) potentiated the effect of the $TNF-{\alpha}$ on NO production but had no additional effect on PDTC-modulated NO production, it is suggested that Hyeolbuchukeo-tang (Xiefuzhuyu-tang) enhances the $TNF-{\alpha}-mediated$ NO production of VSMC by modulating the iNOS activity and the stability of iNOS transcripts in activated VSMC having the elevated intracellular calcium ion. Conclusions : This study suggests that Hyeolbuchukeo-tang (Xiefuzhuyu-tang) has a potential capacity for preventing and treating diseases of the circulation system, including arteriosclerosis.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.254-261
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• 2007

20-O-($\beta$-D-Glucopyranosyl)-20 (S)-protopanaxadiol (IH-901) is one of the major metabolites of ginsenosides from Panax ginseng, and is suggested that IH-901 has been associated with various pharmacological and physiological activities. In this study, we demonstrate that IH-901 induced anti-inflammation in HT-29 human colon adenocarcinoma cells. Our results showed that IH-901 inhibited cell proliferation of HT-29 in a time- and dose-dependent manner. We also found that IH-901 was significantly decreased expression of iNOS compared with non-treated. We observed effect of IH-901 related with inflammatory genes using by cDNA microarray. We were known that the 34 inflammatory genes such as E2F, CDK6, TNF-$\alpha$, and PKC were down-regulated. Thus, these results suggest that IH-901 may have a potential preventive factor to improving cancer induced by chronic inflammation.

• The Journal of Korean Medicine
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• v.26 no.3 s.63
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• pp.13-26
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• 2005

Objectives : Applying herbal-acupuncture using Ursi Fet into Zusanli (UZ) on to the atopic dermatitis (AD) in mice to study changes in external dermal formation, change of leukocytes in vasculature, change of lipid formation in stratum corneum and distribution of ceramide. This study was done through forcing an injury to the mice's back skin which damages the lipid protection formation in the stratum corneum. Methods : The AD which was caused intentionally using the external application on the mice's back skin was treated with VB; the change of leukocytes in the vasculature was identified through optima 5.2 and Student's t-test and the results were made into a dermal formation graph. Results : After dispensing UZ into the AD, the dermal injury decreased. The recovery of the lipid protection formation which includes lipid and ceramide in the stratum comeum (for suppressing acute inflammation due to factors such as PKC, $TNF-\alpha,\;IL-1\beta$, which controlled the secretion of the relating inflammatory cytokine) also went on to show a decrease of both angiogenesis and degranulated mast cells. In addition, the decrease of epithelial injury also caused the growth of cells to decrease in the stratum basale and cytoclasis. In the vasculature, the leukocytes were also decreased na this could relate to a decrease in AD. Conclusions : UZ has an effect on AD by suppressing dermal injury through the recovery of the lipid protection formation in the stratum corneum.

• Journal of Microbiology and Biotechnology
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• v.11 no.5
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• pp.749-755
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• 2001

High Electromagnetic Field (EMF) with an intensity of 1 mT (Tesla) inhibited the growth of both human normal lung and immune T cell down to $20-30\%$, compared to that of an unexposed case. The human T-cells, Jurkat, were more severely affected by EMF than the human lung cells, which showed a relatively slow cell growth and substantial releas of $Ca^+2$ (3.5 times higher than the human T-cells). However, the growth of hepatoma carcinoma, Hep3B, was enhanced by twice that of an unexposed case. The EMF intensity and exposure time did not affect the growth of the cancer cells very much, while it significantly affected the growth of normal cells. Accordingly, it is possible that EMFs may play a role in the initiation of cancer. The EMFs disturbed the signal transduction and membrane systems, such that a five times higher amount of PKC-${\alpha}$ was released from the cell membrane than in the control. Extended exposure to EMFs, for more than 48 hours, also led to 1 $90\%$ necrotic death pattern from apoptotic cell death. Finally, EMF at an intensity of 1mT with a 24-T exposure promoted the differentiation of HL-60 cells to monocytes/macrophages, possibly causing potential acute leukemia.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.349-355
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• 2003

We previously shown that LES contraction depends on $M_3$ receptors linked to PTX insensitive $G_q$ protein and activation of PLC. This results in production of $IP_3$, which mediates calcium release, and contraction through a CaM dependent pathway. In the esophagus ACh activates $M_2$ receptors linked to PTX sensitive $G_{i3}$ protein, resulting in activation of PLD, presumably, production of DAG. We investigated the role of PLC isozymes which can be activated by $G_q$ or $G{\beta}$ protein on ACh-induced contraction in LES and esophagus. Immunoblot analysis showed the presence of 3 types of PLC isozymes, $PLC-{\beta}1$, $PLC-{\beta}3$, and $PLC-{\gamma}1$, but not $PLC-{\beta}2$, $PLC-{\beta}4$, $PLC-{\gamma}2$, $PLC-{\delta}1$, and $PLC-{\delta}2$ from both LES and esophageal muscle. ACh produced contraction in a dose dependent manner in LES and esophageal muscle cells obtained by enzymatic digestion with collagenase. $PLC-{\beta}1$ or $PLC-{\beta}3$ antibody incubation reduced contraction in response to ACh in LES but not in esophageal permeabilized cells, but $PLC-{\gamma}1$ antibody incubation did not have an inhibitory effect. The inhibition by $PLC-{\beta}1$ or $PLC-{\beta}3$ antibody on Ach-induced contraction was antibody concentration dependent. The combination with $PLC-{\beta}_1$ and $PLC-{\beta}_3$ antibody completely abolished the contraction, suggesting that $PLC-{\beta}1$ and $PLC-{\beta}3$ have a synergism to inhibit the contraction in LES. $PLC-{\beta}1$, -${\beta}3$ or -${\gamma}1$ antibody did not reduce the contraction of LES cells in response to DAG ($10^{-6}$ M), suggesting that this isozyme of PLC may not activate PKC. When $G_{q/11}$ antibody was incubated, the inhibitory effect of the incubation of PLC ${\beta}3$, but not of PLC ${\beta}_1$ was additive (Fig. 6). In contrast, when $G_{\beta}$ antibody was incubated, the inhibitory effect of the incubation of PLC ${\beta}_1$, but not of PLC ${\beta}_3$ was additive. This data suggest that $G_{q/11}$/11 or $G{\beta}$ may activate cooperatively different PLC isozyme, $PLC{\beta}_1$ or $PLC{\beta}_3$ respectively.