• The Journal of Korean Medicine
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• v.41 no.4
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• pp.1-11
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• 2020

Objectives: Objectives: The object of this study was to elucidate the possible effects on the pharmacokinetics of tamoxifen after single oral co-administration of Gamisoyo-san (GMSYS) with 2.5 hr-intervals combination therapy of tamoxifen with GMSYS. Methods: After 2.5 hr of 50 mg/kg of tamoxifen treatment, GMSYS 100 mg/kg was administered. The plasma was collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMSYS treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen were analysis as compared with tamoxifen single administered rats. Results: Although single co-administration with GMSYS with 2.5 hr-interval induced increased trends of plasma tamoxifen concentrations, there are no significant changes on the plasma concentrations of tamoxifen were demonstrated in tamoxifen and GMSYS 100 mg/kg co-administrated rats with 2.5 hr-intervals as compared to those of tamoxifen single 50 mg/kg treated rats, and also GMSYS co-administrated rats did not showed any significant changes on the all pharmacokinetic parameters as compared to those of tamoxifen single formula treated rats. Conclusions: According to the this study, single co-administration of GMSYS with 2.5 hr-intervals did not critically influenced on the oral bioavailability of tamoxifen, suggesting GMSYS did not critically influenced on the absorption and excretion of tamoxifen, the oral bioavailability, when they were co-administered with 2.5 hr-intervals, at the dose levels of tamoxifen 50 mg/kg and GMSYS 100 mg/kg.

• Journal of Society of Preventive Korean Medicine
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• v.23 no.1
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• pp.83-94
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• 2019

Objective : This study investigated the effects of concentrated and lyophilized blue honeysuckle powders (BH) on the pharmacokinetics (PK) of sorafenib were observed. Method : The blood was collected at 0.5 hr before single oral treatment of sorafenib (40 mg/kg) or sorafenib with BH (400, 200 and 100 mg/kg) mixed formulas administration, and 0.5, 1, 2, 3, 4, 6, 8 and 24 hrs after the end of single or mixed formula administration. Plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$ of sorafenib were analysis as compared with sorafenib single treatment. Results : Single oral administration of mixed formulas induced significant increases of plasma sorafenib concentrations from 0.5 hr after end of administration throughout all blood collected time points, as compared with sorafenib single formula treated rats, and significant decreases of sorafenib Tmax with increases of Cmax, $AUC_{0-t}$ and $AUC_{0-inf}$ were detected in sorafenib and BH 400 mg/kg mixed formulation treated rats as compared with sorafenib single formula treated rats, respectively. Inaddition, sorafenib and BH 200 or 100 mg/kg mixed formula treated rats also showed significant increases of sorafenib Cmax, $AUC_{0-t}$ and $AUC_{0-inf}$, respectively. Conclusions : According to these results, mixed formulation of BH with sorafenib increased the bioavailability of sorafenib through the increment of the absorptions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.4
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• pp.201-208
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• 2020

The effects of Gamisoyo-san (GMSYS) co-administration within 5 min on the pharmacokinetics (PK) of tamoxifen were observed. After 50 mg/kg of tamoxifen oral treatment, GMSYS 100 mg/kg was orally administered within 5 min to 7-wk old male SPF.VAF Outbred Crl:CD [Sprague-Dawley (SD)] rats. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMSYS treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. Tmax, Cmax, AUC, t1/2 and MRTinf of tamoxifen were analysis as compared with tamoxifen single administered rats. Although co-administration with GMSYS did not critically influenced on the pharmacokinetic parameters of oral tamoxifen, they induced increased trends of plasma tamoxifen concentrations, especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5 hr after end of co-administration with GMSYS as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 10 mg/kg and GMSYS 100 mg/kg within 5 min. It is considered that pharmacokinetic studies should be tested like the effects of GMSYS on the pharmacokinetics of tamoxifen, when they were co-administered with prolonger intervals than Tmax of tamoxifen oral administration (about 2.5 hr-intervals), to achieve the optimal dosing regimen of GMSYS and tamoxifen co-administration.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.1
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• pp.77-85
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• 2023

Objectives This study is designed to evaluate the safety of palmul-tang soft extract in healthy male volunteers. Methods Twelve healthy male volunteers were recruited. And this study was conducted in a single center. As a result of the laboratory test, the safety was evaluated by collecting vital signs of volunteers. Twelve subjects were assigned by serial number according to the registration order. For safety evaluation, blood samples were collected and vital signs were checked four times throughout the test period, including screening, pre-administration, post-administration (after 48 hours) and post-administration (after 7 days). The difference in variables was summarized as the mean±standard deviation. The normality was performed using Kolmogorov-Smirnov and Shapiro-Wilk test. If normality is satisfied, a paired t-test is applied. Otherwise, the Wilcoxon sign rank test, which is a nonparametric method, is applied. The significance was p<0.05. The incidence of all side effects is expressed as a percentage. Results In the case of red blood cell, hemoglobin, and hematocrit values, the result of normality test of variables for the difference value before and after administration is significant level p<0.05. However, all laboratory test values before and after administration did not deviate from the normal range. Also the deviations in the normal range could not be seen as significance related to this clinical trial. And no side effects related to clinical trial drugs were observed. Conclusions The soft extract of palmul-tang was considered safe for healthy male volunteers.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.2
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• pp.94-118
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• 2009

Purpose: Gleditsiae spina (GS) has been used to treat patients with several diseases such as carbuncle, swelling and parasites. Recently GS is known to have anticancer activity in abdominal solid tumor, but the effects of GS on breast cancers is not clarified. For these reasons, we investigated effects of Gleditsiae spina (GS) on gene expression of human breast cancer cells. Methods: We investigated the effects of GS on proliferation of breast cancer cell line, MDA-MB-231. In addition, the genetic profile for the effect of GS on breast cancer cells was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 1,434 genes were up-regulated and 2,483 genes down-regulated in the cells treated with GS. Genes induced or suppressed by GS were all mainly concerned with metabolic process, regulation of biological process and protein binding. The network of total protein interactions was measured using cytoscape program, and some key molecules that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer drug for breast cancer, and also suggest that related mechanisms are involved in regulation of intra-cellular metabolism in breast cancer cells.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.3
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• pp.117-134
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• 2009

Purpose: In the theory of traditional medicine, Scutellariae Radix (SR) can clear away heat and remove dampness, purge the sthenic fire and remove toxic materials, cool blood and stop bleeding to prevent miscarriage. Recently, SR is known to have anti-cancer activity. For this reason, the present author designed to investigate the effect of SR on proliferation rates of cervical cancer cell line, then effects on genetic profile by SR. Methods: The genetic profile for the effect of SR on human derived cervical cancer cell line, SNU-703, was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 519 genes were up-regulated and 606 genes down-regulated in cells treated with SR. Genes induced or suppressed by SR were all mainly concerned with metabolic process, regulation of biological process and protein binding. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as TNFRSF1A, AKT1, MAPK3, and STAT3 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of SR as anti-cancer drug and also suggest that related mechanisms are involved in TNFRSF1A, AKT1, MAPK3, and STAT3 related signalling pathways.

• Genomics & Informatics
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• v.21 no.1
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• pp.9.1-9.13
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• 2023

Matrix metalloproteinase-9 (MMP-9) is a zinc and calcium-dependent proteolytic enzyme involved in extracellular matrix degradation. Overexpression of MMP-9 has been confirmed in several disorders, including cancers, Alzheimer's disease, autoimmune diseases, cardiovascular diseases, and dental caries. Therefore, MMP-9 inhibition is recommended as a therapeutic strategy for combating various diseases. Cinnamic acid derivatives have shown therapeutic effects in different cancers, Alzheimer's disease, cardiovascular diseases, and dental caries. A computational drug discovery approach was performed to evaluate the binding affinity of selected cinnamic acid derivatives to the MMP-9 active site. The stability of docked poses for top-ranked compounds was also examined. Twelve herbal cinnamic acid derivatives were tested for possible MMP-9 inhibition using the AutoDock 4.0 tool. The stability of the docked poses for the most potent MMP-9 inhibitors was assessed by molecular dynamics (MD) in 10 nanosecond simulations. Interactions between the best MMP-9 inhibitors in this study and residues incorporated in the MMP-9 active site were studied before and after MD simulations. Cynarin, chlorogenic acid, and rosmarinic acid revealed a considerable binding affinity to the MMP-9 catalytic domain (ΔG_binding < -10 kcal/ mol). The inhibition constant value for cynarin and chlorogenic acid were calculated at the picomolar scale and assigned as the most potent MMP-9 inhibitor from the cinnamic acid derivatives. The root-mean-square deviations for cynarin and chlorogenic acid were below 2 Å in the 10 ns simulation. Cynarin, chlorogenic acid, and rosmarinic acid might be considered drug candidates for MMP-9 inhibition.

• Journal of Veterinary Science
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• v.25 no.2
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• pp.30.1-30.16
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• 2024

Background: Biofilms, such as those from Staphylococcus epidermidis, are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection. Objectives: Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,O-carboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation. Methods: The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied. Results: Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis. In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production. Conclusions: This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation.

• Korean Journal of Biological Psychiatry
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• v.22 no.2
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• pp.29-33
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• 2015

The brain maintains homeostasis and normal microenvironment through dynamic interactions of neurons and neuroglial cells to perform the proper information processing and normal cognitive functions. Recent post-mortem investigations and animal model studies demonstrated that the various brain areas such as cerebral cortex, hippocampus and amygdala have abnormalities in neuroglial numbers and functions in subjects with mental illnesses including schizophrenia, dementia and mood disorders like major depression and bipolar disorder. These findings highlight the putative role and involvement of neuroglial cells in mental disorders. Herein I discuss the physiological roles of neuroglial cells such as astrocytes, oligodendrocytes, and microglia in maintaining normal brain functions and their abnormalities in relation to mental disorders. Finally, all these findings could serve as a useful starting point for potential therapeutic concept and drug development to cure unnatural behaviors and abnormal cognitive functions observed in mental disorders.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.113-117
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• 2003

The recent development of methods for culturing hair follicles in vitro has proved an important tool to investigate many aspects of drug screening. Hair follicles develop as a result of epithelial-mesenchymal interactions between epidermal keratinocytes and dermal cells. We isolated some follicle cells using explantation and enzymatic digestion method from human scalp hair follicles. So we could culture some follicular cells, such as outer root sheath (ORS) cells, dermal papilla (DP) cells, dermal sheath (DS) cells, matrix cells and melanocytes. To induce hair morphogenesis in vitro the cells were 3-D cultured as skin structures. Moreover, to develop hair follicel organ culture model, we applied dermal equivalent (DE) to culturing hair follicles to expand hair growth period.