• Archives of Pharmacal Research
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• v.23 no.5
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• pp.518-524
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• 2000

We examined the modulation of protein kinase C (PKC) subtypes during apoptosis induced by ginsenoside Rh2 (G-Rh2) in human neuroblastoma SK-N-Bl(2) and rat glioma C6Bu-1 cells. Apoptosis induced by C-Rh2 in both cell lines was confirmed, as indicated by DNA fragmentation and in situ strand breaks, and characteristic morphological changes. During apoptosis induced by G-Rh2 in SK-N-BE(2) cells, PKC subtypes $\alpha$, $\beta$ and $\gamma$ were progressively increased with prolonged treatment, whereas PKC $\delta$ increased transiently at 3 and 6 h and PKC $\varepsilon$ was gradually down-regulated after 6 h following the treatment. On the other hand, PKC subtype $\beta$ markedly increased at 24 h when maximal apoptosis was achieved. In C6Bu-l cells, no significant changes in PKC subtypes $\alpha$, $\gamma$, $\delta$, $\varepsilon$ and $\beta$ were observed during apoptosis induced by G-Rh2. These results suggest the evidence for a possible role of PKC subtype in apoptosis induced by G-Rh2 in SK-N-BE(2) cells but not in C6Bu-1 cells, and raise the possibility that G-Rh2 may induce apoptosis via different pathways interacting with or without PKC in different cell types.

• Journal of Ginseng Research
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• v.33 no.4
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• pp.324-329
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• 2009

Cell-cell adhesion managed by various adhesion molecules is known to be one of pathophysiological phenomena found in numerous immunological diseases such as rheumatoid arthritis and allergic diseases. In this study, we examined the regulatory role of ginsenosides (G)- Rh1, reported to display anti-inflammatory and anti-allergic effects, on CD29-mediated cell adhesion. G-Rh1 significantly suppressed U937 cell-cell adhesion mediated by CD29 but not CD43. It also blocked U937 cell-fibronectin adhesion, mediated by activated CD29, up to 30%. In agreement, this compound also significantly decreased the surface level of CD29 but not CD43 as well as other costimulatory molecules such as CD69, CD80, and CD86. Therefore, these results suggest that G-Rh1 may have inhibitory function on CD29-mediated cell adhesion events, probably contributing to its anti-inflammatory and anti-allergic activities.

• Journal of Korean Neurosurgical Society
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• v.61 no.6
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• pp.669-679
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• 2018

Objective : To compare the spinal bone fusion properties of activin A/BMP2 chimera (AB204) with recombinant human bone morphogenetic protein (rhBMP2) using a rat posterolateral spinal fusion model. Methods : The study was designed to compare the effects and property at different dosages of AB204 and rhBMP2 on spinal bone fusion. Sixty-one male Sprague-Dawley rats underwent posterolateral lumbar spinal fusion using one of nine treatments during the study, that is, sham; osteon only; $3.0{\mu}g$, $6.0{\mu}g$, or $10.0{\mu}g$ of rhBMP2 with osteon; and $1.0{\mu}g$, $3.0{\mu}g$, $6.0{\mu}g$, or $10.0{\mu}g$ of AB204 with osteon. The effects and property on spinal bone fusion was calculated at 4 and 8 weeks after treatment using the scores of physical palpation, simple radiograph, micro-computed tomography, and immunohistochemistry. Results : Bone fusion scores were significantly higher for $10.0{\mu}g$ AB204 and $10.0{\mu}g$ rhBMP2 than for osteon only or $1.0{\mu}g$ AB204. AB204 exhibited more prolonged osteoblastic activity than rhBMP2. Bone fusion properties of AB204 were similar with the properties of rhBMP2 at doses of 6.0 and $10.0{\mu}g$, but, the properties of AB204 at doses of $3.0{\mu}g$ exhibited better than the properties of rhBMP2 at doses of $3.0{\mu}g$. Conclusion : AB204 chimeras could to be more potent for treating spinal bone fusion than rhBMP2 substitutes with increased osteoblastic activity for over a longer period.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1105-1109
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• 2015

Chemoresistance is the most common cause of chemotherapy failure during breast cancer (BCA) treatment. It is generally known that the mechanisms of chemoresistance in tumors involve multiple genes and multiple signaling pathways,; if appropriate drugs are used to regulate the mechanisms at the gene level, it should be possible to effectively reverse chemoresistance in BCA cells. It has been confirmed that chemoresistance in BCA cells could be reversed by ginsenoside Rh2 (G-Rh2). Preliminary studies of our group identified some drugresistance specific miRNA. Accordingly, we proposed that G-Rh2 could mediate drug-resistance specific miRNA and corresponding target genes through the gene regulatory network; this could cut off the drug-resistance process in tumors and enhance treatment effects. G-Rh2 and breast cancer cells were used in our study. Through pharmaceutical interventions, we could explore how G-Rh2 could inhibit chemotherapy resistance in BCA, and analyze its impact on related miRNA and target genes. Finally, we will reveal the anti-resistance molecular mechanisms of G-Rh2 from a different angle in miRNA-mediated chemoresistance signals among cells.

• Journal of the Korean Ceramic Society
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• v.54 no.5
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• pp.388-394
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• 2017

Here, utilizing rhodamine B (RhB) as standard color dye, we examined the photo degradation proficiency of $Ag_2Se-Graphene-TiO_2$ nanocomposites under visible light irradiation; samples were prepared by ultrasonication techniques and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopic investigation and UV-Vis absorbance spectra examination. Our outcomes demonstrate that the $Ag_2Se-G-TiO_2$ nanocomposite showed significant photodegradation efficiency as compared with those of $TiO_2-G$ and $Ag_2Se-G$, with around 85.2% of Rhodamine B (RhB) degraded after 180 min. It is concluded that the $Ag_2Se-G-TiO_2$ nanocomposite is a competent candidate for dye pollutants.

• Proceedings of the Ginseng society Conference
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• 2006.05a
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• pp.3-12
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• 2006

1 The present work was performed to investigate the effects of ginsenoside Rh2 on proliferation, cell cycle-regulation and differentiation of human leukemia HL-60 cells as well as the underlying mechanisms for these effects. 2 Ginsenoside Rh2 potently inhibited the proliferation of HL-60 cells in both a dose- and time-dependent manner with an $IC_{50}$, $20{\mu}M$. 3 DNA flow-cytometry indicated that ginsenoside Rh2 markedly induced a $G_1$ phase arrest of HL-60 cells. 4 Among the $G_1$ phase cell cycle-related proteins, the levels of cyclin-dependent kinase(CDK)4, 6 and cyclin D1, cyclin D2, cyclin D3 were reduced by ginsenoside Rh2, whereas the steadystate levels of CDK2 and cyclin E were unaffected. 5 The protein levels of a CDK inhibitor p16, $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ were markedly increased by ginsenoside Rh2. 6 Ginsenoside Rh2 markedly enhanced the binding of $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ with CDK2 and CDK6, resulting in the reduced activity of both kinases and the hypophosphorylation of Rb protein. 7 We furthermore suggest that ginsenoside Rh2 is a potent inducer of the differentiation of HL-60 cells, based on observations such as a reduction of the nitroblue tetrazolium level, an increase in the esterase activities and phagocytic activity, morphology changes, and the expression of CD11b, CD14, CD64 and CD66b surface antigens. 8 In conclusion, the onset of ginsenoside Rh2-induced the $G_0/G_1$ arrest of HL-60 cells prior to the differentiation is linked to a sharp up-regulation of the $p21^{CIP1/WAF1}$ level and a decrease in the CDK2, CDK4 and CDK6 activities. This is the first report demonstrating that ginsenoside Rh2 potently inhibits the proliferation of human promyelocytic HL-60 cells via the $G_1$ phase cell cycle arrest and differentiation induction.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.89-94
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• 2001

The pharmacokinetics of recombinant human granulocyte colony stimulating factor (rhG-CSF) following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of HM1041l-lyo and HM10411-liq (lyophilized and liquid formulations of rhG-CSF, recently under development by Hanmi Pharmaceutical Company) were studied in rats, and compared with that of Filgrastim (conventional formulation of rhG-CSF on market). The plasma concentration of rhG-CSF was quantified using a specific ELISA. The pharmacokinetic parameters of rhG-CSF, after i.v., i.m. and s.c. administration of Filgrastim, HM1041l-lyo and HM1041l-liq to rats at a rhG-CSF dose of $10\;{\mu}g/kg$, were almost identical among the three formulations. No dose-dependency was observed in the pharmacokinetic parameters of rhG-CSF following i.v. administration in the dose range of $5{\sim}100\;{\mu}g/kg$. rhG-CSF, after i.v. administration of the three preparations at a dose of $10\;{\mu}g/kg$ to rats, was detected at low levels in all of the body tissues with highest tissue/plasma ratio of $0.46{\sim}0.51$ for the kidney at 30 min after the administration. The pharmacokinetics of rhG-CSF, after i.v. administration to mice at a dose of $10\;{\mu}g/kg$, were comparable among the three formulations. In conclusion, HM10411-lyo and HM10411-liq exhibited similar pharmacokinetics for rhG-CSF with Filgrastim regandless of animal species. Considering the fact that HM10411 series, contrary to Filgrastim, are proteins lacking a methionine residue, the methionine moiety in rhG-CSF molecule does not appear to influence the pharmacokinetics of the protein significantly.

• Microbiology and Biotechnology Letters
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• v.32 no.2
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• pp.135-141
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• 2004

Human granulocyte colony-stimulating factor (hG-CSF) is a hematopoiesis agent that principally affects the differentiation of neutrophils in the bone marrow. At present, recombinant hG-CSF is used successfully in the treatment of chemotheraphy-induced neutropenia and its indication has been expanded to bone marrow transplantation and aplastic anemia. In this study, we have constructed rhG-CSF secretion plasmid pYRC1 in which OmpA signal sequence/hG-CSF gene was expressed under the control of the T7 promoter. rhG-CSF produced in E. coli BL21 (pYRC1) grown at $37{\circ}C$ was found in aggregates. However, 15% of the periplasmic protein was soluble rhG-CSF when the E. coli BL21 (pYRC1) was cultured at $25^{\circ}C$ for 7 h in the modified MBL medium containing 10 g/$\ell$ glucose with 10 $\mu$M IPTG induction. The production of soluble rhG-CSF in E. coli BL21 (pYRC1) using fed batch culture was also studied. In the fed batch culture system, the final yield of rhG-CSF produced from E. coli BL21 (pYRC1) was increased from 4.4 mg/$\ell$to 24 mg/$\ell$by controlling the specific growth rate from $0.43 h^{-1}$ to $0.14 h^{-1}$, and optimizing the time of induction.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.313-313
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• 1994

대상환자는 40예중 37예에서 평가가 가능하였고 남녀비는 11:26. 중앙연령 42세 이었으며 대상질환은 위선암 12에, 유방암 10예. 골옥종 5예등 이었다. rhGM-CSF에 의한 부작용은 150.250 $\mu\textrm{g}$/$m^2$/d 용량군에서는 Grade I-II의 전신쇠약감, 근육통.심계항진등이 관찰되었으나 특별한 조치없이 회복되었다. 350$\mu\textrm{g}$/$m^2$/d 용량군에서는 8예에서 WHO grade II-III의 전신쇠약, 전신열감, 흉부압박감, 호흡곤란 등을 호소하였고 1예에서 투여 1일러 WHO gradeIII의 피부반응이 나타났으며, 이 중 2예에서는 rhGM-CSF를 250 $\mu\textrm{g}$/$m^2$/d로 감량투여후 상시 증상이 소실되었다. rhGM-CSF 투여전의 대조기와 투여기의 혈액학적 소견 비교시. 평균 중성구 최저치는 세 용량군에서 모두 관찰기에 비해 시험기어서 증가하였고. 평균 총 백혈군 최저치는 150.350 $\mu\textrm{g}$/$m^2$/d 용량군은 차이가 있었고 250 $\mu\textrm{g}$/$m^2$/d 용량군은 차이가 있었으나 통계적 유의성은 없었다. 비혈구치가 최저치에서 4.000/㎣ 이상으로 회복되는 평균일수와 호중구치가 최저치에서 2.000/㎣ 이상으로 회복되는 평균일수는 세 용량군 모두에서 관찰기어 비해 시험기에서 증가하였다. 고용량 항암약물요법후 중성구 감소에 의한 발열은 rhGM-CSF 비투여기에서 18예. rhGM-CSF 투여기에서 8예 관찰되었다고 발열기간은 각각 5-7일. 2-3일 이었다. 임상 양상은 세 용량군 간 차이가 없었으나, 시험기에서 발열의 발현율이 낮았으며, 발열일 수와 항생제 사용일 수가 짧았다. 결론: 골수억제 조절 효과는 용량에 따른 혈액소견에 미치는 영향, 부작용, 감염의 빈도, 감염발생에 따른 항생제 사용기간 등을 고려하여 그 임상 유효성 평가시, 제 3상 시험에 사용할 권장량 (recommended dose) 은 250 ug/$m^2$/d $\times$ 10d 으로 관찰되었다.

• Journal of Embryo Transfer
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• v.12 no.1
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• pp.117-122
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• 1997

The objective of this study was to enhance the pregnancy rate of repeat-breeder Hanwoo with gonadotropin-releasing hormone(Gn-RH) at the time, dose and site of administration.The results obtained were summaried as fallows:1.Ovulation time and pregnancy rate following GnRH administration time was 46.0, 27.4, 42.0 and 43.2hr and 33.3, 57.1, 37.5 and 40.0% at non-treatment, estus, 1st A' and 2nd Al treatment, respectively.2. Ovulation in repeat-breeder was induced 100% within 24hr with GnRH administration at the time of estrus.3. Ovulation time and pregnancy rate following GnRH adminstration dose and site was 25.2, 32.6, 17.6 and 27.6hr, and 28.6, 42.9, 75.0 and 66.7% at 50$\mu$g+IU, 50$\mu$g+IM, 100$\mu$g+IU and 100$\mu$g+IM treatments, respectively. It is concluded that GnRH administration for repeat-breeder was enhanced the pregnancy rate when treated with 100$\mu$g intrauterine at the time of estrus.