• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.48-55
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• 2010

Neural progenitor cells (NPCs) differentiate into astrocytes, neurons and oligodendrocytes, which is controlled by various factors in brain. Recent evidences suggest that small molecules modulating the proliferation and differentiation of NPCs may have therapeutic value as well as the potential use as chemical probes. Phylligenin is a lignan with anti-inflammatory activity that is isolated from the fruits of Forsythia koreana. We investigated effects of phylligenin on proliferation and differentiation of NPCs. Treatment of phylligenin decreased the number of proliferating NPCs in culture without effects on the differentiation and survival of neural cells such as neurons and astrocytes. To examine the mechanism of the decreased NPCs number, we performed cell cycle analysis. Proliferation of NPCs was decreased via G1-S transition block by phylligenin treatment, and it was mediated by the increase of p21 level. However, phylligenin did not induce apoptosis of NPCs as determined by TUNEL assay and PARP cleavage. We also found that viability of glioma cell lines such as C6 and U87MG glioma cells, but not that of primary neuron and astrocyte, was inhibited by phylligenin. These results suggest that phylligenin selectively inhibits proliferation of rapidly growing cells such as neural stem cells and glioma cells. Given that the possible role of brain tumor stem cells in the pathology of brain cancers, the inhibitory effects of phylligenin might be useful in the development of new therapeutic agents against brain cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2291-2295
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• 2016

Small molecule tyrosine kinase inhibitors targeting HER 2 receptors have emerged as an important therapeutic approach in inhibition of downstream proliferation and survival signals for the treatment of breast cancers. Recent drug discovery efforts have demonstrated that naturally occurring polyphenolic compounds like delphinidin have potential to inhibit proliferation and promote apoptosis of breast cancer cells by targeting HER2 receptors. While delphinidin may thus reduce tumour size, it is associated with serious side effects like dysphonia. Owing to the narrow therapeutic window of delphinidin, the present study aimed to identify high affinity compounds targeting HER2 with safer pharmacological profiles than delphinidin through virtual screening approaches. Delphinidin served as the query parent for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. The compounds retrieved were further subjected to Lipinski and Verber's filters to obtain drug like agents, then further filtered by diversity based screens with a cut off of 0.6. The compound with Pubchem ID: 91596862 was identified to have higher affinity than its parent. In addition it also proved to be non-toxic with a better ADMET profile and higher kinase activity. The compound identified in the study can be put to further in vitro drug testing to complement the present study.

• The Journal of Internal Korean Medicine
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• v.27 no.2
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• pp.444-458
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• 2006

In the Present study, the therapeutic hypolipemic effect of water extract of Saengjinyanghyl-tang (SJYHT), a herbal extract mixture for treatment of diabetes in oriental medicine was tested in Streptozotocin-induced diabetic hyperlipemic SD rats. For detect the therapeutic effects, the test articles were once a day dosed for 28 days by gastric gavage at a dosage 1000, 500 and 250mg/kg from 25 days after STZ-dosing, and the changes on body weight and gains, serum LDL, HDL, Triglyceride and Total Cholesterol levels were observed In addition, the effects of test articles were compared to that of Simvastatin, a well known hypolipemic agents 10mg/kg-dosing group. Base on these results, although no meaningful effects were detected on the serum HDL levels, it is concluded that Saengjinyanghyul-tang water extracts have relatively good favorable effect treatment of STZ-induced diabetic hyperlipemia because they showed clear evidences inhibit the increase of serum LDL, Triglyceride and Total Cholesterol levels. Therefore, it is expected that Saengjinyanghyul-tang extract has favorable potency to development hypolipemic drugs. In addition, about 1000mg/kg of Saengjinyanghyul-tang extracts have similar effect compared to that of Simvastatin 10mg/kg. The effective dosage of Saengjinyanghyul-tang water extracts in the present study was considered as below 250mg/kg.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.392-398
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• 2007

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by inflammatory cell infiltration in the skin. This study was performed to assess the therapeutic effects of YHYBT on the DNCB-induced dermatitis in NC/Nga mice, characterized by the onset of AD along with an increase the number of Th2 cells and dysregulation of inflammaroty mediators including cytokines and chemokines. YHYBT administration significantly reduced clinical dermatitis severity including pruritus, edema, eczematous and erythema. Histological findings indicated that the thickening of epidermis/dermis and dermal infiltration of inflammatory cells including mast cells were dramatically reduced. The suppression of dermatitis by YHYBT was accompanied by a decrease in the total number of immune cells in drained lymph node (DLN) and skin. Especially CD3+, CD4+ and CD3+CD69+ T cells in PBMC and DNL were greatly reduced. The level of IL-4 in CD3/CD28 activated splenocyte was downregulated, whereas that of IFN-'처리불가‘ was increased. Furthermore, the expression of eotaxin2 and CCR3 in skin were significanlty decreased. These data suggest that YHTBT may be effective therapeutic agents for the treatment of AD.

• Parasites, Hosts and Diseases
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• v.42 no.1
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• pp.27-34
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• 2004

We investigated the optimal culture conditions for Cryptosporidium muris in a human stomach adenocarcinoma (AGS) cell line by determining the effects of medium pH and of selected supplements on the development of C. muris. The optimum pH of the culture medium required for the development of C. muris was determined to be 6.6. The number of parasites significantly increased during cultivation for 72 hr (p < 0.05) at this level. On the other hand, numbers decreased linearly after 24 hr of incubation at pH 7.5. When cultured in different concentrations of serum, C. muris in media containing 5% FBS induced 4-7 times more parasites than in 1% or 10% serum. Of the six medium supplements examined, only 1 mM pyruvate enhanced the number of C. muris in vitro. Transmission electron microscopic observation showed the developmental stages of C. muris in the cytoplasm of the cells, not in an extracytoplasmic location. The growth of C. muris in AGS cells provides a means of investigating its biological characteristics and of testing its response to therapeutic agents. However, a more optimized culture system is needed for the recovery of oocysts on a large scale in vitro.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.347-353
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• 2019

Stings of jellyfish, which frequently occur in a warm season, cause severe pain, inflammation and sometimes irreversible results such as the death. Harmful venoms from jellyfish, therefore, have been studied for finding the therapeutic agents to relieve pain or to neutralize toxic components. However, it is still unclear if and how jellyfish venom reveal neuronal toxicity even though pain induction seems to result from the activation of nociceptors such as nerve endings. In this study, using HT-22 cell line, we investigated neurotoxic effects of the venom of Chrysaora pacifica (CpV) which appears in South-East ocean of Korea. In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, CpV significantly reduced the viability of HT-22 cells in a dose-dependent manner. Additionally, in 2',7'-Dichlorofluorescin diacetate fluorescence test under the culture condition lacking dominant inflammatory factors, CpV remarkably increased the production of intracellular reactive oxygen species (ROS). Reduced responsive fluorescence to Rhodamine123 and increased expression of intracellular cytochrome c were also observed in HT-22 cells treated with CpV. These indicate that CpV-reduced viability of HT-22 cells may be due to the activation of apoptotic signalings mediated with oxidative stress and mitochondrial dysfunction. Furthermore, removing Ca²⁺ ion or adding N-acetyl-Lcystein remarkably blocked the CpV effect to reduce the viability of HT-22 cells. The findings in this study clearly demonstrate that CpV may activate Ca²⁺-mediated ROS signalings and mitochondrial dysfunction resulting in neuronal damage or death, and suggest that blocking Ca²⁺ pathway is a therapeutic approach to possibly block toxic effects of jellyfish venoms.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.321-325
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• 2009

5-HT$_{2C}$ receptors have been considered as therapeutic targets for the treatment of various central nervous system disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. We chemically synthesized KKHQ80114 (K14) and KKHQ80109 (K09), selective 5-HT$_{2C}$ agonists, with the purpose of developing therapeutic agents for the treatment of obesity. The objective of this work is to investigate analytical methods of these compounds in the plasma and urine of rats by gas chromatography/mass spectrometry. In this experiment, K14 was determined in plasma and urine by using K09 as internal standard. Calibration curves give a good linearity in plasma (r$^2$=0.9993) and urine (r$^2$=0.9988). Among hexane, ethyl acetate and diethyl ether, the highest peak was observed in diethyl ether. However, ethyl acetate was used since more interfering peaks were observed with diethyl ether. Inter-day precision and accuracy were determined in the ranges of 50-500 ng/mL for plasma and 10-500 ng/ml for urine. Quantitation limits were 50 ng/mL plasma and 25 ng/ mL urine. These data may be applicable for further studies of these compounds including absorption and metabolism due to no pharmacokinetic or analytical data available.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.327-331
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• 2009

5-HT$_{2C}$ receptors have been considered as therapeutic targets for the treatment of various central nervous system disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. We chemically synthesized KKHQ80109 (K09) and KKHQ80114 (K14), selective 5-HT$_{2C}$ agonists, with the purpose of developing therapeutic agents for the treatment of obesity. The objective of this work is to investigate pharmacokinetic parameters and bioavailability of K09 and K14 in rats given orally or intravenously. Oral administration of 20 mg/kg K09 results in 4.11 hr of the terminal half-life and 89.16 ng/mL of C$_{max}$ at 5.00 hr (T$_{max}$). The terminal half-life of K14 was 3.83 hr with 215.81 ng/mL of C$_{max}$ at 3.33 hr (T$_{max}$) after oral dosing of 20 mg/kg K14, indicating that K14 is more rapidly absorbed than K09. Bioavailability showed 0.17-0.21 for K09 and 0.19-0.23 for K14. Urinary excretion of parent K09 and K14 was less than 1%, indicating that K09 and K14 undergo very extensive hepatic metabolism.

• Journal of Sasang Constitutional Medicine
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• v.20 no.2
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• pp.119-128
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• 2008

1. Objectives This case study describes a successful treatment process of a Soyangin patient with somatoform autonomic dysfunction symptoms using Soyangin therapeutic measures, including administration of Dokhwaljihwang-tang (獨活地黃湯) and Sibyimijihwang-tang (十二味地黃湯). 2. Methods The patient was treated with several constitutionally discriminated medicinal agents (獨活地黃湯, 十二味地黃湯) and acupunctural therapy accompanied by simultaneous western medical management. The visual analogue scale (VAS) was applied to assess the severity of flushing. 3. Results and Conclusions As flushing was one of the chief complaints, the patient was treated with Soyangin therapeutic measures including Dokhwaljihwang-tang and Sibyimijihwang-tang. The patient responded positively to the therapy, but further studies are anticipated for more definitive conclusions.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.159-166
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• 2000

Kunitz-type soybean trypsin inhibitor (SBTI) and chondroitin sulfate (A, and C type) were conjugated using sodium periodate method. And the physicochemical, pharmacokinetic properties and immunogenecity of the conjugates (Chon-A-SBTI or Chon-C-SBTI) were characterized. We expected the conjugation using chondroitin sulfate to reduce the immunogenecity and to improve the pharmacological effect. As the results, the mean molecular weight of the conjugate highly increased. After I.V. injection of the radiolabeled conjugates or native SBTI into mice, it was found that native SBTI showed rapid elimination from plasma, whereas Chon-A-SBTI and Chon-C-SBTI were slowly eliminated. Organ distribution of the two agents at 30 min after I.V. injection was different : Chon-A-SBTI or Chon-C-SBTI accumulated to a large extent in the liver (13% in Chon-A-SBTI and 16% in Chon-C-SBTI), whereas native SBTI was taken up more rapidly by the kidney (107% dose/g of tissue) and excreated into the urine (26%). In addition we evaluated the therapeutic value of the conjugates by using the sublethal septic shock model caused by pseudomonal elastase and tested the immunogenecity by passive cutaneous anaphylaxis shock (PCA). The conjugates were more effective than native SBTI against pseudomonal elastase induced septic shock in guinea pig. In case of the conjugates, the pharmacological and therapeutic effect lasted over 3 hours long. In immunogenecity test, both of the conjugates showed the reduction of their immunogenecity, especially Chon-A-SBTI looked most effective.