• Journal of Ginseng Research
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• v.44 no.3
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• pp.399-404
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• 2020

Korean ginseng (Panax ginseng) is associated with a variety of therapeutic effects, including antioxidative, anti-inflammatory, vasorelaxative, antiallergic, antidiabetic, and anticancer effects. Accordingly, the use of ginseng has reached an all-time high among members of the general public. However, the safety and efficacy of ginseng in transplant recipients receiving immunosuppressant drugs have still not been elucidated. Transplantation is the most challenging and complex of surgical procedures and may require causation for the use of ginseng. In this regard, we have previously examined the safety, immunological benefits, and protective mechanisms of ginseng with respect to calcineurin inhibitor-based immunosuppression, which is the most widely used regimen in organ transplantation. Using an experimental model of calcineurin inhibitor-induced organ injury, we found that ginseng does not affect drug levels in the peripheral blood and tissue, favorably regulates immune response, and protects against calcineurin inhibitor-induced nephrotoxicity and pancreatic islet injury. On the basis of our experimental studies and a review of the related literature, we propose that ginseng may provide benefits in organ transplant recipients administered calcineurin inhibitors. Through the present review, we aimed to briefly discuss our current understanding of the therapeutic benefits of ginseng related to transplant patient survival.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.405-411
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• 2006

Epinastine is an antiallergic drug effective for bronchial asthma, allergic rhinitis, urticaria and dermatitis. Epinastine is topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from the mast cell. The purpose of the present study was to evaluate the bioequivalence of two epinastine hydrochloride tablets, Alesion Tablet (Boehringer Ingelheim Korea Ltd.) and S-napine tablet 10 mg(Sam Chun Dang Pharm. Co., Ltd), according to the guidelines of the Korea Food and Drug Administration(KFDA). The release of epinastine from the two epinastine formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media(pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, $23.35{\pm}1.57$ years in age and $66.29{\pm}10.61kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 20 mg as epinastine hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of epinastine in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t.\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Alesion tablet, were 1.50, 1.46 and -13.48% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25(e.g., log 0.95$\sim$log 1.12 and log 0.93$\sim$log 1.10 for $AUC_t\;and\;C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating S-napine tablet 10 mg was bioequivalent to Alesion tablet.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.309-316
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• 2017

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel with modest permeability to calcium ions. It is involved in intracellular calcium signaling and is therefore important in processes such as thermal sensation, skin barrier formation, and wound healing. TRPV3 was initially proposed as a warm temperature sensor. It is activated by synthetic small-molecule chemicals and plant-derived natural compounds such as camphor and eugenol. Schisandra chinensis (Turcz.) Baill (SC) has diverse pharmacological properties including antiallergic, anti-inflammatory, and wound healing activities. It is extensively used as an oriental herbal medicine for the treatment of various diseases. In this study, we investigated whether SC fruit extracts and seed oil, as well as four compounds isolated from the fruit can activate the TRPV3 channel. By performing whole-cell patch clamp recording in HEK293T cells overexpressing TRPV3, we found that the methanolic extract of SC fruit has an agonistic effect on the TRPV3 channel. Furthermore, electrophysiological analysis revealed that ${\gamma}$-schisandrin, one of the isolated compounds, activated TRPV3 at a concentration of $30{\mu}M$. In addition, ${\gamma}$-schisandrin (${\sim}100{\mu}M$) increased cytoplasmic $Ca^{2+}$ concentrations by approximately 20% in response to TRPV3 activation. This is the first report to indicate that SC extract and ${\gamma}$-schisandrin can modulate the TRPV3 channel. This report also suggests a mechanism by which ${\gamma}$-schisandrin acts as a therapeutic agent against TRPV3-related diseases.

• The Journal of Pediatrics of Korean Medicine
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• v.19 no.1
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• pp.185-201
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• 2005

Objective : This experimental study was performed to examine the anti-allergic infiammatory effects of Mori Folium. Method : Macrophage 264.7 cells were pretreated for 1hour with Sangyup. After pretreatment, macrophage were incubated with lipopolysaccharide(LPS) $100ng/m{\ell}$ 12h and media collected and $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, IL-10 concentrations in supernatants were measured each by Enzyme linked immuno-sorbent assay. Sangyup were used $1mg/m{\ell}$, $500{\mu}g/m{\ell}$, $250{\mu}g/m{\ell}$, $100{\mu}g/m{\ell}$, $50{\mu}g/m{\ell}$. Hydrocortisones were used $10^{-4}M,\;10^{-5}M,\;10^{-6}M,\;10^{-6}M,\;10^{-6}M$. Results : Macrophage 264.7 cells were pretreated with Hydrocortisones and Sangyup. After pretreatment, macrophage were incubated with lipopolysaccharide(LPS). To investigate the anti-inflammatory effect of Sangyup, we measured the amount of cytokines, and the results are as follows; 1. Mori Folium. showed statistically significant inhibitory effect on antiinflammation in $TNF-{\alpha}(p<0.02)$ in all five concentrations compared with the (-)controls treated with LPS. Mori Folium showed inhibitory effect on antiinflammation in $TNF-{\alpha}$ in similarpattern in all five concentrations compared with the (+)control pretreated with hydrocortisone. 2. Mori Folium. showed statistically significant inhibitory effect on antiinflammation in IL-6(p<0.01) in all five concentrations compared the (-)controls treated with LPS. Mori Folium. showed inhibitory effect on antiinflammation IL-6 similar pattern in all five concentrations compared with the (+)control pretreated with hydrocortisone. 3. Experimental Group pretreated with Mori Folium. showed statistically significant difference of antiinflammation in $IL-1{\beta}$ in concentrations of $50{\mu}g/m{\ell}(p<0.01)$, $250{\mu}g/m{\ell}(p<0.05)$ compared with the (-)control treated with LPS. Experimental Group pretreated with Mori Folium. showed increased level of $IL-1{\beta}$ in all concentrations compared the (+)control treated with hydrocortisone. 4. Experimental Group pretreated with Mori Folium. did not show statistically significant effect on IL-10 compared with the (-)control. Conclusion : By the findings of this experiment, Mori Folium is observed to have antiallergic and antiinflammation effect.

• The Journal of Korean Medicine
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• v.18 no.2
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• pp.167-186
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• 1997

The inhibitory activity of Aquillariae Lignum (Thymelaeaceae) on type Ⅰ immediate hypersensitivity of the anaphylactic type in the wistar rat model of passive cutaneous anaphylaxis, an IgE-mediated, mast cell-dependent reaction. Administered orally at 250, 500 mg/kg body weight 1 h before the challenge, Aquillariae Lignum potently inhibited PCA in rats which disodium cromoglycate showed poor inhibitory activity. Aquillariae Lignum inhibited compound 48/80-induced anaphylaxis 100% with a dose of 0.5 g/kg body weight at 1 h before or 5 and 10 min after injection of compound 48/80. Aquillariae Lignum (0.05-1.6 mg/ml) also exhibited the dose-related inhibitory effect on compound 48/80-induced histamine release from rat_peritoneal mast cells. Moreover, it was clearly demonstrated that Aquillariae Lignum and disodium cromoglycate disodium cromoglycate potently inhibited such type Ⅰ allergic reactions as anaphylactic shocks, suggesting that these drugs, at least in part, share the same mechanism of action It is suggested that Aquillariae Lignum may exert a stronger inhibition on the mast cell degranulation process. Since Aquillariae Lignum (1.0 mg/ml) inhibited about 90% of histidine decarboxylase activity, the inhibitory activity of Aquillariae Lignum for histamine release was considered to be derived from the inhibition of histidine decarboxylase activity. It results from increased expression of the mRNA coding for histidine decarboxylase, as assessed by Northern blot analysis after a 12 h incubation to P-815 cells with dexamethasone plus 12-O-tetradecanoylphorbol-13-acetate. The addition of Aquillariae Lignum to P-815 cells with dexamethasone plus 12-O-tetradecanoyl-phorbol-13-acetate, significantly inhibited the histidine decarboxylase gene expression. Tumor necrosis $factor-{\alpha}$ was not constitutively expressed in P-815 cells. Substance P selectively activates the tumor necrosis $factor-{\alpha}$ gene expression in P-815 cells. Aquillariae Lignurm inhibited substance P-induced tumor necrosis $factor-{\alpha}$ gene expression. Furthennore, The effect of Aquillariae Lignum on the mRNA expression of novel protein kinase C ${\delta}$ a major isoform of mast cells, was examined by Northern blot analysis. The expression of novel protein kinase C ${\delta}$ mRNA in the presence of Aquillariae Lignum was significantly lower than in the absence of Aquillariae Lignum. These results suggest the possibility that the inhibition of allergic reaction by Aquillanae Lignum should be regulated by tumor necrosis $factor-{\alpha}$ and novel protein kinase C ${\delta}$.

• Journal of Pharmaceutical Investigation
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• v.31 no.1
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• pp.57-62
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• 2001

Azelastine, a phthalazinone derivative, is an antiallergic agent which demonstrates histamine $H_1-receptor$ antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Thus, azelastine may be useful in the management of both asthma and allergic disorders. The purpose of the present study was to evaluate the bioequivalence of two azelastine hydrochloride tablets, $Azeptin^{TM}$ (Bu Kwang Pharmaceutical Co., Ltd.) and $Azela^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $22.44{\pm}2.01$ years in age and $61.99{\pm}6.18\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 1 mg of azelastine hydrochloride per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of azelastine in serum were determined using HPLC with fluorescence detector. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets were -6.45%, -2.60% and -7.14%, respectively, when calculated against the $Azeptin^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 96.65% and 88.47%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 14.40% and 17.65% for $AUC_t\;and\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g., $-14.87{\sim}1.97$ and $-12.92{\sim}7.72$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Azela^{TM]$ tablet is bioequivalent to $Azeptin^{TM}$ tablet.

• Herbal Formula Science
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• v.5 no.1
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• pp.184-202
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• 1997

The results of immune response and antiallergic reaction were as follows. 1. Hemagglutinin titer and hemolysin titer were increased in case of AMR, AR, SNH. But the results were not recognized as having significance. 2. PFC was increased in case of AMR, AR. But the results were not recognized as having significance. 3. RFC was increased in all groups, and the results in the AR, SNH were significant. 4. In experimentation of phagocytic activity in peritoneal exudate cells, AR and SNH showed significant increase. In spleen cells AR and SNH showed significant increase. In monolymphocytus cells AMR, AR and SNH were increased, but result of AMR was of no significance. 5. I examined promotion on spleen cells transformation. As these results, AMR showed increase in $50{\mu}g/m{\ell}$, $5000{\mu}g/m{\ell}$ in comparison with control group. And in $500{\mu}g/m{\ell}$ AMR showed increase in case of 24 hours, 72 hours incubation, but showed decrease in case of 48 hours incubation. AR showed increase in all. In $50{\mu}g/m{\ell}$ SNH showed increase in comparison with control group. And in $500{\mu}g/m{\ell}$, $5000{\mu}g/m{\ell}$ SNH showed increase in case of 24 hours, 48 hours incubation, but showed decrease in case of 72 hours incubation. 6. I examined proliferation of spleen cells. As these results AMR and SNH showed the highest increase in $50{\mu}g/m{\ell}$, but showed the lowest increase in $5000{\mu}g/m{\ell}$. AR showed the highest increase in $500{\mu}g/m{\ell}$, but this result was the almost same in $50{\mu}g/m{\ell}$, $5000{\mu}g/m{\ell}$. And AMR, AR, SNH showed higher activity in Lipopolysaccharide than Concanavalin A. 7. In all groups results of PCA were decreased in 2 week. In 4 week AR and SNH showed decrease, but AMR didn't show change. In 6 week AR and SNH showed decrease, but on the contrary AMR showed increase. 8. In experimentation on histamine contents, AMR showed significant increase at first agent contact. And AR, SNH showed decrease at first agent contact, but these results were of no importance. At second agent contact AMR showed decrease, but was of no importance. AR, SNH showed significant decrease. At third agent contact, AMR showed significant increase. AR, SNH showed decrease, but these results were of no importance. From above these results, AR and SNH showed good effects on immunoreaction. And all the herb medicines in this examination showed good effects in promotion on spleen cells transformation and proliferation of spleen cells, especially activated B-cells. AR, SNH showed good effects on anti-allergic reaction, but AMR was almost inefficient. Accordingly I think that AR shall be used in disease bringing about a lowering of immunity, that is, AR shall be used in strengthening the body resistance. And I think that SNH shall be used in eliminating pathogenic factors with strengthening the body resistance. It is necessary to a deep study in future.

• Bulletin of the Korean Chemical Society
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• v.31 no.1
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• pp.52-58
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• 2010

Human histamine H1 receptor (HHR1) is a G protein-coupled receptor and a primary target for antiallergic therapy. Here, the ligand-based three-dimensional pharmacophore models were built from a set of known HHR1 inverse agonists using HypoGen module of CATALYST software. All ten generated pharmacophore models consist of five essential features: hydrogen bond acceptor, ring aromatic, positive ionizable and two hydrophobic functions. Best model had a correlation coefficient of 0.854 for training set compounds and it was validated with an external test set with a high correlation value of 0.925. Using this model Maybridge database containing 60,000 compounds was screened for potential leads. A rigorous screening for drug-like compounds unveiled RH01692 and SPB00834, two novel molecules for HHR1 with good CATALYST fit and estimated activity values. The new lead molecules were docked into the active site of constructed HHR1 homology model based on recently crystallized squid rhodopsin as template. Both the hit compounds were found to have critical interactions with Glu177, Phe432 and other important amino acids. The interpretations of this study may effectively be deployed in designing of novel HHR1 inverse agonists.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.134-143
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• 2017

Background: The prevalence of allergic inflammatory diseases such as atopic dermatitis (AD), asthma, and allergic rhinitis worldwide has increased and complete recovery is difficult. Korean Red Ginseng, which is the heat-processed root of Panax ginseng Meyer, is widely and frequently used as a traditional medicine in East Asia. In this study, we investigated whether Korean Red Ginseng water extract (RGE) regulates the expression of proinflammatory cytokines and chemokines via the mitogen-activated protein kinases (MAPKs)/nuclear factor kappa B ($NF-{\kappa}B$) pathway in allergic inflammation. Methods: Compound 48/80-induced anaphylactic shock and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced AD-like skin lesion mice models were used to investigate the antiallergic effects of RGE. Human keratinocytes (HaCaT cells) and human mast cells (HMC-1) were also used to clarify the effects of RGE on the expression of proinflammatory cytokines and chemokines. Results: Anaphylactic shock and DNFB-induced AD-like skin lesions were attenuated by RGE administration through reduction of serum immunoglobulin E (IgE) and interleukin (IL)-6 levels in mouse models. RGE also reduced the production of proinflammatory cytokines including $IL-1{\beta}$, IL-6, and IL-8, and expression of chemokines such as IL-8, thymus and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC) in HaCaT cells. Additionally, RGE decreased the release of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), $IL-1{\beta}$, IL-6, and IL-8 as well as expressions of chemokines including macro-phage inflammatory protein $(MIP)-1{\alpha}$, $MIP-1{\beta}$, regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, and IL-8 in HMC-1 cells. Furthermore, our data demonstrated that these inhibitory effects occurred through blockage of the MAPK and $NF-{\kappa}B$ pathway. Conclusion: RGE may be a useful therapeutic agent for the treatment of allergic inflammatory diseases such as AD-like dermatitis.

• Journal of Life Science
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• v.27 no.4
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• pp.476-481
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• 2017

Polyphenols are secondary metabolites produced by higher plants and have been used as antiallergic, anticancer, antihypertensive, antiinflammatory, antimicrobial and antioxidant agents. They are generally divided into flavonoids and non-flavonoids. The antimicrobial activity of flavonoids are stronger than that of non-flavonoids. The skeleton structures of flavonoids possessing antimicrobial activity are chalcone, flavan-3-ol (catechin), flavanone, flavone, flavonol and proanthocyanidin. The flavonols are shown antibacterial activity against several gram-positive bacteria (Actinomyces naeslundii, Lactobacillus acidophilus and Staphylococcus aureus) and gram-negative bacteria (Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella melaninogenica and Prevotella oralis). Among of non-flavonoids, caffeic acids, ferulic acids and gallic acids showed antimicrobial activity against gram-positive (Listeria monocytogenes and S. aureus) and gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). These are found to be more efficient against the E. coli, L. monocytogenes, P. aeruginosa and S. aureus than antibiotics such as gentamicin and streptomycin. The kaempferol and quercetin showed synergistic effect with ciprofloxacin and rifampicin against S. aureus and methicillin resistant S. aureus (MRSA). Epigallocatechin gallate (EGCG) acts synergistically with various ${\beta}-lactam$ antibiotics against MRSA. In particular, the epicatechin, epigallocatechin (EGC), EGCG and gallocatechin gallate from Korean green tea has antibacterial activity against MRSA clinical isolates and the combination of tea polyphenols and oxacillin was synergistic for all the clinical MRSA isolates.