• 대한본초학회지
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• 제26권4호
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• pp.39-47
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• 2011

Objective: The roots, leaves, flowers, stems and seeds of Cirsium japonicum var. ussuriense are often used in treatment of human diseases such as hemorrhage, blood congestion and inflammation. Focusing our attention on natural and bioavailable sources of antioxidants and anti-inflammation, we undertook to investigate the antioxidant and anti-inflammatory properties of Cirsium japonicum var. ussuriense used as a folk medicine in Korea. Methods: The extracts of the leaves, stems, flowers, seeds and roots from C. japonicum var. ussuriense were prepared by extracting with water or 80% ethanol. Total flavonoids and polyphenols were measured by a colorimetric assay. The free radical scavenging activity of the extract was analyzed by the DPPH (1,1-diphenyl-2-picryl hydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and Griess reagent assay. An oxidative product of nitric oxide (NO), was measured in the culture medium by the Griess reaction. The level of prostaglandin $E_2$ ($PGE_2$) was measured by enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were measured by Western blot analysis. Results: Total flavonoid and polyphenol amounts of the leaves (CLE) and flowers (CFE) showed higher than those of the seed extract (CSE), stem extract (CSTE) and roots (CRE). CLE and CFE also showed the high antioxidant activities such as DPPH, NO-like and ABTS radical scavenging activity. An antioxidant activities of these water extracts showed higher than those of 80% ethanol extracts. We investigated the anti-inflammatory effects of CLE on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. CLE significantly suppressed the levels of the inflammatory mediators such as NO and prostaglandin $E_2$ ($PGE_2$) in dose dependant. Furthermore, the levels of iNOS and COX-2 protein expressions were markedly suppressed by the treatment with CLE extract in a dose dependent manner. Conclusions: These results suggest that CLE water extract has a higher anoxidant and anti-inflammatory activity, these properties may contribute to the oxidative and inflammatory related disease care.

• 한국미생물·생명공학회지
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• 제38권1호
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• pp.77-83
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• 2010

산사자는 전 세계적으로 이용되는 있는 식용/약용 생물자원 중 하나이다. 본 연구에서는 산사자의 유용 생리활성 검토를 위한 연구의 일환으로, 산사자의 methanol 추출물 및 이의 n-hexane, ethylacetate, butanol 분획물 및 물 잔류물을 조제하여 항생제 다제내성 Pseudomonas aeruginosa 및 Candida sp.를 포함하는 다양한 병원성 및 식중독 미생물에 대한 항균활성을 평가하였다. 산사자의 methan이 추출물은 그람 양성 및 음성의 다양한 세균에 대해 항균활성을 나타내였고, 이의 분획물 중 ethylacetate 및 butanol 분획물은 Listeria monocytogen, Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis, Salmonella typhimurium, Proteus vulgaris, Escherichia coli는 물론 10종의 항생제 내성 병원성 Pseudomonas aeruginosa에 대해서도 우수한 항세균 활성을 나타내었다(최소생육억제농도 1.0~7.5 mg/mL). 또한 ethylacetate 및 butan이 분획물은 일부의 Candida sp.에 대해서도 항균활성을 나타내였다. 한편 n-hexane 분획물을 제외한 산사자 methan이 추출물 및 분획물들은 $500\;{\mu}g/mL$ 농도까지 인간적혈구에 대한 용혈현상을 보이지 않았으며, n-hexane 분획물은 $500\;{\mu}g/mL$ 농도에서 약 9.9%의 미미한 용혈활성을 나타내었다. 이러한 결과는 산사자가 다양한 세균의 제어는 물론 항생제 내성 Pseudomonas aeruginosa 제어를 위한 생물자원으로 개발 기능함을 제시하고 있다.

• Archives of Pharmacal Research
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• 제28권5호
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• pp.626-635
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• 2005

Liposome as a carrier of topotecan (TPT), a promising anticancer drug, has been reported in attempt to improve the stability and antitumor activity of TPT. However, the biodistr ibution pattern of TPT liposome in vivo and PEG-modified liposome containing TPT have not been studied systemically. In this paper, the in vitro stability and in vivo biodistribution behavior of several liposomes containing TPT with different lipid compositions and PEG-modification were studied. Compared with the 'fluid' liposome (S-Lip) composed of soybean phosphatidylcholine (SPC), the 'solid' liposome (H-Lip) composed of hydrogenated soybean phosphatidylcholine HSPC decreased the leaking efficiency of TPT from liposome and enhanced the stability of liposome in fetal bovine serum (FBS) or human blood plasma (HBP). The results of biodistribution studies in S$_{180}$ tumor-bearing mice showed that liposomal encapsulation increased the concentrations of total TPT and the ratio of lactone form in plasma. Compared with free TPT, S-Lip and H-Lip resulted in 5- and 19- fold increase in the area under the curve (AUC$_{0\rightarrow\propto}$), respectively. PEG- modified H-Lip (H-PEG) showed 3.7-fold increase in AUC$_{0\rightarrow\propto}$ compared with H-Lip, but there was no significant increase in t$_{1/2}$ and AUC$_{0\rightarrow\propto}$ for PEG-modified S-Lip (S-PEG) compared with S-Lip. Moreover, the liposomal encapsulation changed the biodistribution behavior, and H-Lip and H-PEG dramatically increased the accumulation of TPT in tumor, and the relative tumor uptake ratios were 3.4 and 4.3 compared with free drug, respectively. There was also a marked increase in the distribution of TPT in lung when the drug was encapsulated into H-Lip and H-PEG. Moreover, H-PEG decreased the accumulation of TPT in bore marrow compared with unmodified H-Lip. All these results indicated that the membrane fluidity of liposome has an important effect on in vitro stability and in vivo biodistribution pattern of liposomes containing TPT, and PEG-modified 'solid' liposome may be an efficient carrier of TPT.

• 한국식품저장유통학회지
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• 제21권5호
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• pp.727-734
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• 2014

식용 및 약용으로 이용되고 있는 우엉 지하부의 혈전 관련 활성과 항산화 활성을 평가하고자, 우엉의 ethanol 추출물 및 이의 순차적 유기용매 분획물을 조제하여 혈액응고 저해 활성, 혈소판 응집저해 활성, 인간 적혈구 용혈활성 및 in-vitro 항산화 활성을 평가하였다. 먼저 우엉 추출 수율은 10.94%로 다른 식용 및 약용식물보다 높았으며, ethanol 추출물의 경우 total polyphenol 함량은 5.01 mg/g으로 낮았으나, 694.53 mg/g의 높은 총당 함량을 나타내었다. 순차적 유기용매 분획의 경우, n-hexane, ethylacetate(EA), n-butanol 분획 수율은 각각 1.62, 0.42 및 5.98%로 나타났으며, 물 잔류물은 85.38%였다. 우엉 시료들의 혈액응고 저해활성을 TT, PT, aPTT를 측정한 결과, ethanol 추출물에서는 유의적인 활성이 나타나지 않았으나, EA 분획에서 강력한 TT, PT, aPTT 연장효과를 확인하였으며, 농도 의존적 혈액응고 저해활성을 확인하였다. 한편 물 잔류물에서는 내인성 혈액응고인자 활성화에 의한 aPTT 감소효과를 확인하여 혈전생성 촉진효과가 있음을 확인하였다. 혈소판 응집저해 활성평가의 경우, 우엉 ethanol 추출물 및 분획물들은 임상에서 사용하는 항혈소판제인 아스피린보다 강력한 저해효과를 나타내었으며, 특히 EA 분획은 정제되지 않은 상태에서도 아스피린의 2배 이상의 강력한 혈소판 응집저해능을 나타내었다. 또한 항산화 활성 평가 결과, EA 분획물은 DPPH 음이온, ABTS 양이온, nitrite에 대해 우수한 소거능 및 환원력을 나타내었다. 또한 우엉 추출물과 분획물들은 0.5 mg/mL 농도까지 인간 적혈구에 대한 특이한 용혈활성을 나타내지 않았다. 상기 결과들은, 우엉 EA 분획물이 천연물 유래의 안전한 항혈전제로 개발 가능함을 제시하고 있다.

• 대한한의학방제학회지
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• 제23권2호
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• pp.189-198
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• 2015

Objectives : Sparganii Rhizoma is frequently used in traditional herbal medicine for treatment of blood stasis, amenorrhea and functional dyspepsia and has been reported to exhibit anti-oxidant, anti-proliferation and anti-angiogenesis peoperties. In this study, we investigated the cytoprotective effect and underlying mechanism of Sparganii Rhizoma water extract (SRE) against oxidative stress-induced mitochondrial dysfunction and apoptosis in hepatocyte. Methods : To determine the effects of SRE on oxidative stress, we induced synergistic cytotoxicity by co-treatment of arachidonic acid (AA) and iron in the HepG2 cell, a human derived hepatocyte cell line. Results : Treatment of SRE increased relative cell viability and altered the expression levels of apoptosis-related proteins such as Bcl-xL, Bcl-2 and procaspase-3. And SRE also inhibited the mitochondrial dysfunction and excessive reactive oxygen species production induced by AA+iron. In addition, SRE activated of AMP-activated protein kinase (AMPK), a potential target for cytoprotection, by increasing the phosphorylation of AMPKα at Thr-172. Morever, SRE increased phosphorylation of acetyl-CoA carboxylase, a direct downstream target of AMPK. Conclusion : These results indicated that SRE has the ability to protect against oxidative stress-induced hepatocyte damage, which may be mediated with AMPK pathway.

• 대한한의학회지
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• 제19권2호
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• pp.373-390
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• 1998

35 theses conducted in Korea on the topic of senescence or anti-oxidant were classified on the basis of research methods, animals used for the experiments, and research items. Evaluating these research works with respect to the Free Radical Theory, the following conclusions were reached. 1. Of the 17 theses written in the Oriental medicine aspect, three theses used a single herb, nine theses used a complex prescription, four theses concentrated on the usage of the medicinal acupuncture, and one research paper focused on using scientific components. Common objection of these papers were on the verification of the efficacy of herbs. 2. Of the 18 these written in the Western medicine aspect, five theses used a single drug, seven theses conducted a research on the changes due to senescence, and 6 papers were on variety of topics. The main focus of these works were on the mechanism and pathology related to the senescence rather than on the suppression of senescence. 3. Among the theses written in the Oriental medicine perspective, a total of 48 herbs were utilized. 26 of these herbs has a tonification function on the Kidney. Six out of nine complex prescription mentioned above has a function of tonifying the Kidney. 4. With respect to the research subjects used on the experiments, 8 theses have used Senescence-Accelerated mice, 13 theses have used Sprague-Dawley mice, and remaining 7 papers have used human or other animals. 5. These are the categorization of the research items used: the weight (11) and weight changes of the visceral organs (9), the measurement of the content of peroxide-disease (9), the measurement of enzyme vitality (21), the blood and urine test (10), the experiment concerning immune system (3), the influence on the hepatic capability of metabolizing foreign substance (3), the effect on hepatic cell protection (3), the measurement of both the suppression of Free Radical and ability to create Free Radical (2), the measurement of effect of suppresing MDA(malondialdehyde) (4), the effect of eliminating DPPH Radical (2), and experiements about the functions (2). 6. The rate of vitalization of well known anti-oxidants such as Superoxide dismutase (SOD), Protein-bound SH, Nonprotein-bound SH, Glutathione(GSH), Catalase, and etc. were tested in 17 theses. Considering the conclusions mentioned above, the theses related to the senescence published in Korea elected different animals used for experiments, research items and the methods of research, the end result seems to be a lack of objectivity. Thus, I would argue that research methods to overcome such a deficiency need to be developed systematically.

• Journal of Pharmaceutical Investigation
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• 제41권3호
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• pp.191-196
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• 2011

In this study simple and sensitive high performance liquid chromatographic method using a commercially available column, was developed and validated for the determination of zolpidem tartrate in human plasma. The developed method with suitable validation was applied to a bioequivalence study of two different kinds of zolpidem tartrate. Two different formulations containing 10 mg of zolpidem tartate (CAS : 99294-93-6) were compared in 24 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, cross-over design in 24 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 12 h. The mean $AUC_{0-12h}$, $C_{max}$, $T_{max}$ and $T_{1/2}$ were $676.6{\pm}223.4$ $ng{\cdot}h{\cdot}mL^{-1}$, $177.4{\pm}34.2$ $ng{\cdot}mL^{-1}$, and $0.8{\pm}0.4$ and $3.5{\pm}2.1$, respectively, for the test formulations, and $640.7{\pm}186.6$ $ng{\cdot}h{\cdot}mL^{-1}$, $193.0{\pm}64.5$ $ng{\cdot}mL^{-1}$, and $0.9{\pm}0.4$ and $2.7{\pm}0.9$, respectively, for the reference formulation. Both primary target parameters $AUC_{0-12h}$ and $C_{max}$ were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of $AUC_{0-12h}$ and $C_{max}$ were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of zolpidem tartate are considered to be bioequivalent.

• 혜화의학회지
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• 제4권2호
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• pp.335-336
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• 1996

Artemisinin, a new antimalarial to treat patients infected with strains of Plasmodium jalciparum, derived from the plant Artemisia annua Linn, has immunopharmacologic actions such as enhence the PHA -induced lymphocyte transformation rate, increased the weight of spleen but reduced the weight of thymus, reduced phagocytic function of peritoneal macrophage, remarkably reduced the level of serum IgG and hemolysin fonning capacity (sentitized with SRBC), inhibited the activity of Ts cells of donor mice by supraoptimal immunuization(SOI), but enhenced activity of Ts cells of recipient mice by SOI. These results suggested that Ts cells may be the target cells of artemisinin. To the serum complement C3 level of plasmodium berghei-infeted mice, artemisinin (i. m,) could remarkly increase it. The artemisinin also obviously reduced the prostaglandin E(PGE) in the mouse hind paw swelling induced by carrageenin. Numerous studies have demonstrated that pharmacologic doses of PGE attenuate the development of immunocomplex nephritis. Some autologous immune mechanisms may be invoolved In the pathogensis of some types of glomurulonephritis. Glomerular abnormalities can be induced in animals by variety of immunological manipulations. The resulting disorder has many clinical and pathogical similarities to the disease in human. Our purpose was therefore to test the ability of the artemisinin to lessen the severity of rabbit IgG accelerated nephrotoxic serum glomerulonephritis in mice model. Mice which had treated with rabbit IgG and NTS, administrated with saline, showed Significant inceases of urinary protein, cholesterol level, and decrease of serum albumin in NS group. On the contrary, By i.g. adminstration of artemisinin at dose of 12.5, 25 and 50 mg/kg for 14 days after NTS injection, shown that artemisinin inhibited the nephritic changes in some parameters by means of urinary protein(p<0.05, p<0.01) and serum choleterol(p<0.05, p<0.01) and albumin (p<0.05, p<0.01), blood urea nitrogen (p<0.05, p<0.01), serum albumin(p<0.05, p<0.01); Cyclophosphamide(i.p. 10mg/kg for 14d) had almost same effect as the artemisinin had. Morphological studies shown that The picture of kidney from the mouse with NTS-nephritis accerated with rabbit IgG, treated with i.g. saline as the control, the mesangiocapillary were enlarged and proliferated; There were inflammatory cells infiltrating around the glomeruli; The ethelial cell were proliferated in the wall of Bowman's capsule. Histopatholological picture of kidney from the NTS-nephritis accerated with rabbit IgG mouse treated with i.p. 10mg/kg cyclophosphamide as the positive control. No siginicant histopathological evidence were found. Treaded with i.p. 12.5mg/kg artemisinine, the picture shown that mesangiocapillary were lightly proliferated; There were inflammatory cells infiltrating around the glomeruli; Treaded with i.p. 25mg/kg artemisinine, The picture shown that the mesangiocapillary were lightly proliferated; Treaded with i.p. 50mg/kg artemisinine, The picture shown that both the mesangiocapillary proliferated and the inflammatory cells infiltrating around the glomeruli are less than treated with saline, 12.5 and 25 mg/kg artemisinine. On the basis of these studies we conclude that the artemisinin can relieve pathological change caused by NTS-nephritis aacerated with rabbit IgG.

• Journal of Radiation Protection and Research
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• 제27권3호
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• pp.181-188
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• 2002

방사선 생체 손상에 대한 방호 효과를 나타내는 천연물을 검색하기 위한 일환으로 한의학에서 보혈양혈 탕제에 널리 사용되는 백작약 (Paeonia japonica)을 열수총추출물, 에탄올분획, 조다당분획으로 나누어 방사선에 의한 산화적 손상 경감 효과를 검정하였다. 사람 림프구에서 단세포전기영동 (single cell gel electrophoresis; comet assay)을 수행하여 DNA 손상 경감정도를 관찰하였으며, 마우스에 백작약 추출물을 투여한 다음 8 Gy의 감마선을 조사한 후 간에서 지질과산화 정도를 살펴보았다. 에탄올분획 처리군에서 높은 DNA 손상 경감효과를 확인할 수 있었으며, 지질과산화 억제작용 및 라디칼 소거효과 또한 에탄올분획이 높은 효과를 나타내어 에탄올분획이 방사선 방호에 주된 역할을 하는 것으로 사료된다. 이상의 결과로 보아 백작약은 방사선의 산화절 손상에 대하여 효과적으로 세포 DNA를 방호하고, 생체막의 주성분인 지질의 과산화를 억제하는 것으로 관찰되어 특히, 독성이 거의 없는 천연물이라는 관점에서 방사선 방호제로 적용이 가능할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제43권3호
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• pp.359-366
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• 1996

연구배경 : 기관지천식 등의 알레르기 질환의 병인에 호산구는 중요한 역할을 하며 화학주성의 연구는 새로운 변조성분에 대한 호산구의 반응을 평가하는데 in vivo 실험에 앞서 유용한 방법론으로 쓰이고 있다. 탈과립화된 비만세포와 활성화된 T 림프구가 기관지 천식의 병태생리에 관계하며 tryptase는 비만세포의 활성화후 분비되는 단백분해효소 중 하나로써 호산구의 화학주성과 활성화에 영향을 미칠 것으로 생각된다. 본 연구의 목적은 단백분해효소의 대표격인 trypsin과 chymotrypsin이 호산구의 화학주성과 활성화에 어떤 역할을 하는지 알고자 함에 있다. 방법 : 호산구의 분리는 혼합된 과립구로부터 호중구를 제거하는 면역자기방법으로 하였고 화학주성은 multi-well micro-Boyden chamber로 정량하였으며 ECP 유리정량은 fluoroimmunoassay를 이용하였다. 결과 : 호산구는 trypsin에 화학주성을 보였고 최대의 반응이 $1000{\mu}g/ml$에서 $56.52{\pm}14.50$/HPF로 양성대조군인 PAF에 필적하였다. 반면 chymotrypsin에 대해서는 화학주성을 보이지 않았다. Trypsin으로 처리한 호산구의 ECP 분비능은 trypsin 10, 100, $1000{\mu}g/ml$ 농도에서 음성대조군에 비하여 각각 2.7, 3.7, 6배 높았다. Soybean trypsin inhibitor로 전처치하였을 때 ECP의 분비능은 감소되었으며 $1000{\mu}g/ml$ 농도에서 음성대조군과 유의차이가 없었다. 결론 : trypsin은 호산구에 화학주성을 일으킬 수 있으며 호산구를 활성화하여 호산구 과립단백의 하나인 ECP를 분비하게 한다고 사료된다. 반면 chymotrypsin은 호산구에 대한 직접적인 작용은 없는 것으로 보인다.