• Natural Product Sciences
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• 제20권1호
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• pp.58-64
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• 2014

In this study, edible protopanaxadiol saponin enriched fraction were prepared by ultrafiltration (UF). Ginseng extract was prepared from mixtures of ginseng main root and rootlet (root: rootlet = 4 : 6). UF system was used the four-piston Diaphragm pump equipped with 5 kDa pore size Hydrosart Cassette made by regenerated cellulose acetate (CA) or 3 kDa pore size Hollow Fiber cartridge made by polyethersulfone (PES). Total ginsenoside contents of concentrated fraction by UF system was found to higher, compared to before those of untreated method. Especially, processing of UF showed the increase of PPD-type ginsenoside, while PPT-type ginsenoside was gradually decreased by both 3 kDa and 5 kDa membrane. After removal of 80% water by the 5 kDa Hydrosart Cassette and by 3 kDa Hollow Fiber cartridge, ginsenoside Rb1 content was higher 37.2 mg/g and 25.3 mg/g than 20.8 mg/g in untreated process. The ratio of Rb1 to Rg1 (Rb1/Rg1) and PPD- to PPT- type ginsenoside (PPD/PPT) were higher in inner fluid of ginseng extract after UF by 3 kDa cartridge (47.1 and 23.5, respectively) and 5 kDa Cassette (25.3 and 11.9, respectively) than those of before UF (5.7 and 3.7, respectively). PPD-type ginsenoside enriched fraction by UF system could be developed as a new ginseng material in food and cosmetic industrials.

• 대한본초학회지
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• 제25권1호
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• pp.55-63
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• 2010

Objectives : The object of this study was to verify the inhibitory effect of a decoction of Eucommiae ulmides OLIVER (EU) and Dipsacus asperoides C. Y. Cheng et T.M.Ai (DA) on Collagen II-induced Arthritis Mice (CIA mice). Methods : DBA/1OlaHsd mice were immunized with bovine type II collagen. Boostnig same collagen 21 days later, arthritis was induced and then administrated orally the extract of EU+DA (200 or 50 mg/kg) once a day for 4 weeks and compared with that of methotrexate (MTX, 0.3 mg/kg) as a positive control. Results : Administration of EU+DA suppressed the inflammatory progression of CIA mice and the results were 1. Arthritis index of CIA mice was decreased. 2. EU+DA decreased the production of TNF-$\alpha$, IL-6, IL-$1{\beta}$ in the serum of CIA mice. 3. EU+DA decreased the level of IgM. 4. EU+DAincreasaed $CD3^+$, $CD4^+$, $CD4^+$/CD25 but decreased $CD19^+$, $CD3^+/CD49b^+$(NKT), $CD3^-/CD49b^+$(NK), $B220^+/CD23^+$ in PBMC of CIA mice. 5. EU+DA decreased $CD3^+$, $CD4^+$, $CD3^+/CD69^+$ of paw joint in CIA mice. 6. EU+DA decreased subsynovial inflammation. Conclusions : This results demonstrated that extract of EU+DA suppressed the inflammatory progression of CIA mice and supported further studies are required to clarify a mechanism of therapeutic role.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제1권1호
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• pp.37-44
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• 1998

목 적: H. pylori 감염증에 대한 치료요법은 성인의 경우 여러가지 방법이 알려져 있으나 국내에서 소아를 대상으로 한 H. pylori 치료결과에 대한 연구보고는 미미하다. 이에 저자들은 소아에서의 H. pylori 감염증에 대한 치료결과 및 재발률을 조사하고, 아울러 효과적이고 경제적인 치료방법을 찾아보고자 하였다. 대상 및 방법: 1993년 11월부터 1997년 8월까지 복통 또는 상부위장관 출혈을 주소로 연세의대 세브란스병원 소아과에 내원하여 상부위장관 내시경검사와 Warthin-Starry 은염색, CLO검사 결과 H. pylori 감염증으로 진단된 환아 120례 중 치료 후 추적관찰이 가능하였던 75례를 대상으로 하였다. 대상환아는 남아가 39례, 여아가 36례였으며, 평균연령은 $11.4{\pm}2.5$세였다. 대상환아들은 초기약제로 DA($Denol^{(R)}$과 amoxycillin), OA(omeprazole과 amoxycillin) 또는 DC($Denol^{(R)}$과 clarithromycin) 등 세가지 요법중 한가지를 투여하였고, 제균에 실패한 환아에 대해서는 DAM($Denol^{(R)}$과 amoxycillin, metronidazole), DC, OA, OC(omeprazole과 clarithromycin) 중 한가지를 2~4주간 투여하였으며, 치료종결 4주 후 H. pylori 제균 여부를 진단시와 동일한 방법으로 판정하였다. 결 과: 대상환아의 상부위장관질환은 만성 결절성위염 46례, 위궤양 9례, 십이지장궤양 6례, 표재성위염 6례 및 정상 8례 등이었다. DA는 69례에서 투여되어 이중 63례(91%)에서 H. pylori가 제균되었고, DAM은 DA에 실패한 2례중 1례, DC는 초기 치료한 4례중 3례(75%)와 DA에 실패한 2례중 1례(50%)에서, OA는 초기치료한 2례에서, OC는 DA에 실패한 1례에서 모두 제균되였다. 치료 후 H. pylori 제균에 실패한 환아는 7례(DA 6례, DC 1례) 였으며, 이중 3례는 2차 치료(DAM, DA 및 DC 각 각 1례)로 제균되었고, 나머지 4례(DAM 2차요법 1례, 추적 불능 3례)에서는 제균되지 않았다. 치료 후 H. pylori가 제균되었으나 수 개월이 지나 재발된 환아는 4례(5.3%)로 치료 종결 후 3개월에서 3년 사이에 재발되었다. 재발된 4례중 2례는 2차 요법(OC, DA 각각 1례)으로 제균되었고, 나머지 2례(DC 2차요법 1례, 추적불능 1례)에서는 제균되지 않았다. 결 론: bismuth subcitrate와 amoxycillin의 두약제 요법은 H. pylori의 제균율이 91%로 높고 재발률도 5.3%로 낮으며, 또한 경제적이기 때문에 소아의 H. pylori 감염증에 대한 초기 치료제로 선택되어 질 수 있는 유용한 치료방법중의 하나로 생각된다.

• Biomolecules & Therapeutics
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• 제5권2호
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• pp.202-210
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• 1997

Protective effect of DA-9601, an extract of Artemisia Herb, against ethanol-induced gastric mucosal injury was evaluated in rats. In the prophylactic study, DA-9601 exhibited total protection (99.4%) against absolute ethanol-induced gastropathy, And the protective effect of DA-9601 lasted up to 2 hours, which was longer than those of other contemporary mucoprotectants. In the treatment study, DA-9601 significantly facilitated the healing of 70% ethanol-induced mucosal damage, which was superior to cetraxate, a commonly used anti-ulcer drug. The mechanisms of mucoprotection of DA-9601 were also assessed. DA-9601 increased the release of prostaglandin E$_2$ from murine neutrophils in a dose-dependent manner in vitro. The cytoprotective effect of DA-9601 against ethanol-induced mucosal damage was significantly diminished by the concommitant injection of N$\omega$-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, i.v.), a non-specific nitric oxide (NO) synthase inhibitor, while it was not affected by preinjection of indomethacin (5 mg/kg, s.c.), a prostaglandins-depletor. And it was found that DA-9601 significantly enhanced adaptive cytoprotective action of 10% ethanol against absolute ethanol (56.9$\pm$6.5 vs 23.0$\pm$3.3 mm$^2$, p<0.05, mean$\pm$SEM), though its exact underlying mechanism remains to be clarified. The present fin[lings demonstrate that DA-9601 exerts gastroprotecticv actions for the stomach against ethanol through several different underlying mechanisms, in which prostanglandins and NO are involved. In conclusion, the results obtained suggest that DA-9601 can be useful both in prevention and treatment of ethanol-induced gastric damage.

• Biomolecules & Therapeutics
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• 제11권1호
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• pp.41-50
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• 2003

General pharmacological properties of DA-8159, a new pyrazolopyrimidinone derivative were examined in laboratory animals to investigate its safety profile. The oral administration of DA-8159 (1, 5 or 30 mg/kg) in mice and rats had no effect on general behaviors and central nervous system of the animals in test systems, such as hexobarbital-induced sleeping time, motor coordination, normal body temperature, writhing syndromes induced by 0.75% acetic acid solution, chemo-shock produced by pentetrazole solution and rotar rod test. Anesthetized cats treated intravenously with DA-8159 (0.1, 0.3, 1, 3 or 10 mg/kg) showed transient and mild decrease in blood pressure. However, heart rate, respiration rate and tidal volume were not changed by intravenous DA-8159. In the isolated organs including ileum, heart (sinus rate of atria and contractility of papillary muscle), trachea of guinea pigs and phrenic nerve of rats, DA-8159 ($10^{-8}$ ∼$10^{-5}$ mg/L) did not elicit any effect or inhibitory action on the chemically or electrically stimulated contraction. DA-8159 did not influence gastric secretion, pH and total acid output in rats and intestinal propulsion in mice. The administration of DA-8159 in rats had no effect on the platelet aggregation induced by ADP in rabbit plasma, urinary volume and electrolyte ion ($Na^{+}$, $K^{+}$, $Cl^{-}$) excretion in rats. Prothrombin time (PT) of the rats showed a mild but significant increase after administration of DA-8159. Activated partial thromboplastin time (APTT), however, was not affected by DA-8159. These results indicate that DA-8159 does not exert any of serious pharmacological effects.

• 생명과학회지
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• 제19권9호
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• pp.1232-1238
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• 2009

신경전달물질의 분비는 시냅스전 신경말단의 active zone에 있는 다양한 단백질들에 의해 조절된다. 도파민은 정신분열병, 약물중독과 같은 여러 가지 행동, 정신질환의 병태생리와 연관된 필수적인 신경전달물질이다. 저자들은 본 연구에서 신경 전달물질 분비와 관련된 주요 유전자가 결여 된 knockout (KO) 생쥐의 시냅토좀(synaptosome) 도파민 분비를 측정하였다. 시냅토좀 도파민 흡수와 분비는 [$^3H$]-도파민과 관류실험을 이용하여 시행, 측정하였다. 17 KO 생쥐 가운데 3 종류의 생쥐에서 그들의 littermate 대조군과 비교하였을 때 변화된 도파민 분비를 보였다. $Rim1{\alpha}$ KO에서 세포막 탈분극에 의한 [$^3H$]-도파민은 유의하게 감소되었으며, 또한 $Rim1{\alpha}$의 도파민 신경에서의 조건 KO에서는 생리적 완충용액에 의한 기본적인 도파민 분비 및 세포막 탈분극에 의한 도파민 분비 모두가 유의하게 감소되어 있었다. neurexin3의 도파민 신경에서의 조건 KO에서는 세포막 탈분극에 의한 도파민 분비의 증가를 보였다. 이 데이터들은 도파민 분비와 글루타메이트, GABA와 같은 전통적 신경전달물질 분비의 유사성과 차별성을 설명한다. 결론적으로, $Rim1{\alpha}$와 neurexin3는 시냅스전 도파민 분비의 중요한 조절자이며 신경계 질환과 연관될 가능성이 있다.

• 한국응용과학기술학회지
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• 제34권3호
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• pp.673-682
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• 2017

식물 및 동물성 단백질 유래 펩타이드 형태의 단백질 가수 분해물들은 항산화, 고혈압 완화, 면역조절, 진통완화 및 항균작용 등 생리활성이 있는 것으로 알려져 왔다. 본 연구는 연산오계란 단백질 가수 분해물을 Ultrafiltration를 이용하여 HDS(분획되지 않은 가수 분해물), 1 kDa, 5 kDa, 10 kDa, 50 kDa로 분획된 기능성 펩타이드의 DPPH radical scavenging activity, superoxide anion radical scavenging activity, hydroxyl radical scavenging activity 및 $Fe^{2+}$ chelation ability을 평가하였다. 그 결과 DPPH radical scavenging activity 최대값은 1 kDa(70.83 %), hydroxyl radical scavenging activity 최대값은 5 kDa (47.01 %), superoxide anion radical scavenging activity 최대값은 5 kDa(40.57 %), $Fe^{2+}$ chelation ability 최대값은 5 kDa(29.87 %)로 나타났다. Ultrafiltration를 이용하여 fractionation된 단백질 가수 분해물의 항산화 저해 능력 $IC_{50}$ 평가하였다. 그 결과 HDS의 최대값은 superoxide anion radical scavenging activity($IC_{50}$, 5.42 mg/ml)이고, 1 kDa의 최대값은 $Fe^{2+}$ chelation ability($IC_{50}$, 1.67 mg/ml)이고, 5 kDa의 최대값은 $Fe^{2+}$ chelation ability($IC_{50}$, 2.09 mg/ml)이고, 10 kDa의 최대값은 $Fe^{2+}$ chelation ability($IC_{50}$, 2.61 mg/ml)이고, 50 kDa의 최대값은 $Fe^{2+}$ chelation ability($IC_{50}$, 4.53 mg/ml)이다. 그러므로 본 연구 결과를 바탕으로 5 kDa를 이용하여 오계란 단백질에서 분획한 펩타이드는 항산화 기능성 식품소재로서 활용할 가치가 높을 것으로 기대한다.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.236-243
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• 1993

Immunologic potential of DA-125, a new anthracycline antitumor antibiotic, was investigated using guinea pigs and mice. In antigenicity experiments, guinea pigs were sensitized subcutaneously with DA-125 or DA-125 incorporated in complete Freund's adjuvant (CFA) once a week for three weeks. No systemic anaphylaxis was induced by intravenous injection of DA-125 or DA-125 incubated with guinea pig serum after 3 weeks from the last sensitization. None of sera of these animals showed any passive cutaneous anaphylactic reaction (PCA) when DA-125 or DA-125 incubated with guinea pig serum was used as a challenging antigen in homologous PCA experiment. On the other hand the treatment of guinea pigs with ovalbumin Incorporated in CFA induced systemic anaphylactic reaction when challenged by intravenous injection of 5 mg/body of ovalbumin. Immunodiffusion test revealed no precipitating antibodies as detected in guinea pigs sensitized with DA-125. In 24-hour heterologous PCA reaction with sera of C57BL/6 mice immunized with DA-125 or DA-125 mixed with aluminum hydroxide gel (Alum), None of sera showed positive reaction when DA-125 or DA-125 incubated with rat serum was used as a challenging antigen. Sera of animals immunized with a mixture of ovalbumin and alum showed positive PCA reaction when 5 mg/body of ovalbumin was injected as a challenging antigen. In lymphocyte proliferation tests, spleen lymphocyte proliferation to PHA and LPS was similarly impaired by 12 mg/kg of DXR or 36 mg/kg of DA-125, and the immunodepressive activity of DA-125 showed a dose-dependent manner. From these results, it could be concluded that immunosupression of DA-125 would be comparable to that of DXR and that DA-125 would not induce systemic allergic reaction in its clinical use.

• BMB Reports
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• 제52권5호
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• pp.336-341
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• 2019

The cGAS-STING pathway plays an important role in pathogen-induced activation of the innate immune response. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) found predominantly in the synovial fluid of osteoarthritis (OA) patients increases the expression of catabolic factors via the toll-like receptor-2 (TLR-2) signaling pathway. In this study, we investigated whether 29-kDa FN-f induces inflammatory responses via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway in human primary chondrocytes. The levels of cGAS and STING were elevated in OA cartilage compared with normal cartilage. Long-term treatment of chondrocytes with 29-kDa FN-f activated the cGAS/STING pathway together with the increased level of gamma-H2AX, a marker of DNA breaks. In addition, the expression of pro-inflammatory cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF-2), granulocyte colony-stimulating factor (G-CSF/CSF-3), and type I interferon ($IFN-{\alpha}$), was increased more than 100-fold in 29-kDa FN-f-treated chondrocytes. However, knockdown of cGAS and STING suppressed 29-kDa FN-f-induced expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ together with the decreased activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and inhibitor protein ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$). Furthermore, NOD2 or TLR-2 knockdown suppressed the expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ as well as decreased the activation of the cGAS/STING pathway in 29-kDa FN-f-treated chondrocytes. These data demonstrate that the cGAS/STING/TBK1/IRF3 pathway plays a critical role in 29-kDa FN-f-induced expression of pro-inflammatory cytokines.

• 대한화장품학회지
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• 제42권3호
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• pp.235-245
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• 2016

본 연구에서는 히알루론산나트륨(sodium hyaluronate, HA)을 효소 분해하여 분자량 크기(1, 10, 50, 100, 660, 및 1500 kDa) 별로 제조한 뒤 콜라겐 합성 및 항염증 활성에 미치는 영향과 피부투과도를 조사하였다. 이들 HA는 인간피부세포인 Hs68 세포에 세포독성을 나타내지 않았다. 콜라겐 생합성능은 1500 kDa, 50, kDa HA가 각각 59, 50%로 콜라겐 생합성 촉진능이 우수한 것으로 나타났다. 분자량 크기에 따른 HA의 피부투과도를 측정한 결과 660 또는 1500 kDa의 HA은 2% 미만의 미미한 투과율을 보였으나, 저분자 HA (1, 10, 또는 50 kDa)은 시간이 지남에 따라 투과율이 증가하는 것을 확인하였다. 마우스 대식세포인 RAW 264.7 세포에서 HA 분자량 크기에 따른 항염증 효과를 확인한 결과, 50 kDa HA가 농도 의존적으로 nitric oxide 및 tumor necrosis factor-${alpha}$ 합성을 저해하여 다른 분자량의 HA (1, 10, 및 100 kDa)에 비해 가장 큰 항염증 효능을 나타냈다. 현재까지 효소(hyaluronidase) 처리하여 제조된 다양한 크기의 분자량(1, 10, 50, 100, 660, 1500 kDa)의 HA 중 50 kDa HA가 collagen의 합성, 항염증 및 피부 흡수도에 대한 종합적인 평가를 한 사례는 없었다. 따라서 이러한 연구결과는 50 kDa의 HA가 인간피부세포에서 콜라겐 합성을 증진시키고, 피부 투과율을 높으며 피부 주름을 유발하는 염증반응을 억제함으로써 피부노화 및 주름 개선용 화장품소재로 개발될 수 있는 가능성을 보여준다.