• 한국양식학회지
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• 제19권1호
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• pp.33-39
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• 2006

Anticoagulant activities of a fermented edible brown alga, Laminaria ochotensis was investigated. L. ochotensis was fermented with 15% sugar (w/v) at $25^{\circ}C$ for 10 weeks. Anticoagulant activity was measured from the supernatant of algal mixture at biweekly intervals up to $10^{th}$ week by activated partial thromboplastin (APTT), prothrombin time (PT) and thrombin time (TT) assay using citrated human plasma. Sample having high APTT activity $(6^{th}\;week)$ was filtered, ethanol precipitated and freeze-dried. The polysaccharide compound having anticoagulant activity was purified by DEAE ion exchange chromatography followed by Sepharose-4B gel filtration chromatography. Anticoagulant activity, polysaccharide concentration, and heparin like activity were determined for the collected fractions by APTT, $phenol-H_2SO_4$, and glycosaminoglycan assay, respectively. The anticoagulant activity assay showed that the activity was increased up to $6^{th}$ week, and decreased thereafter. The concentration of our purified compound was $31.0{\mu}g/ml$ and showed higher APTT activity than commercial heparin. At the same concentration of $31.0{\mu}g/ml$, the heparin showed 186.5 sec activity while our purified compound showed an activity of 386 sec. Single spot on agarose gel electrophoresis showed that the compound was purified and polyacrylamide gel electrophoresis (PAGE) results revealed that the molecular mass of the purified polysaccharide compound was between 60 and 500 kDa. Therapeutic interest of the algal polysaccharide as an anticoagulant has recently been in highlighted. This purified anticoagulant compound from fermented L. ochotensis can be used as a model for anticoagulant agent or could be developed as an anticoagulant agent. This study can be extended to identify the structure and chemical composition of the purified polysaccharide, and to establish a relationship between structure and the function of the identified anticoagulant compounds.

• Biomolecules & Therapeutics
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• 제8권4호
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• pp.349-353
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• 2000

Mefenamic acid has been widely used as clinical drug for anti-inflammatory and analgesic. This drug was known to non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and indomethacin. Although the drugs which comprise this group are of diverse chemical structures, they all share the antipyretic, analgesic and anti-inflammatory actions which are characteristic of aspirin. Action of this drugs is caused by inhibitory effect of biosynthesis of prostaglandin that are synthesized from arachidonic acid via the endoperoxide biosynthesis pathway, the initial step of which is catalysed by cyclooxygenase. Mefenamic acid has more potent inhibitory action of prostaglandin biosynthesis than aspirin. Therefore, mefenamic acid is expected to have anticoagulant activity as aspirin-like drugs. This study was carried out to investigate the sinthesis of mefenamic acid derivatives from mefenamic acid and aromatic compound of antioxidant and its antioxidative and anticoagulant activities. Synthesis of mefenamic acid derivatives was conformed by conjugation as using esterification method. Biological activities was examined using effect of anticoagulant on bleeding time and effect of antioxidant by TBA method. As a result, SJ-202 showed strong antioxidative activity and anticoagulant activity among tested 4 compounds and exhibited similar activity to aspirin at anticoagulant activity.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.669-674
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• 2002

Glycosaminoglycans (GAGs) were isolated from the porcine testis, and their immuno-modulating and anticoagulant activity was investigated. From anion exchange chromatography (Dowex Macropolous Resin) used for further isolation of porcine testis GAGs (PT-GAGs), two fractions (PT-GAG-1.5 and PT-GAG-16) eluted by different salt concentration were obtained. In immunomodulating activity test, PT-GAG-1.5, but not PT-GAG-16, significantly enhanced the growth of murine peritoneal macrophages. In addition, treatment with PT-GAG-1.5 induced the production of cytokines, interleukin-1$\beta$ (IL-1$\beta$), interferon-${\gamma}$ (IFN-${\gamma}$) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$), from murine microphages. Unexpectedly, both of PT-GAGs had no effect on the growth of murine splenocytes. The anticoagulant activity of PT-GAG-1.5 and PT-GAG-16 was examined by activated partial thromboplastin time (aPTT) assay and thrombin time (TT) assay. Both of PT-kGAGs significantly increased the clotting times of aPTT and TT in a dose-dependent manner. The anticoagulant activity of PT-GAG-16 was found to be higher than that of PT-GAG-1.5. These results suggest that PT-GAGs possess biological activities such as immunomodulating activity and anticoagulant activity.

• KSBB Journal
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• 제13권4호
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• pp.378-382
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• 1998

Agar hydorlysates or agarooligosaccharides from agar prepared by Cytophaga agarase showed eight spots on TLC plate and the degree of polymerization of the spots were in the reange of 2.5 - 6.5. Each component of the hydrolysate as tested the several functionalities such as antimicrobial activity, anticavity activity, and anticoagulant activity. The anticativity activity and anticoagulant acitvity were found in all fractions of hydrolysates and several spot on TLC, whereas the anticoagulant activity was very low.

• 한국식품과학회지
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• 제29권4호
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• pp.817-822
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• 1997

구름버섯 자실체에서 분리된 항응고성 다당류의 혈액응고 저해기작을 검토하였다. 항응고성 다당(CV-40-Va-1)은 vWF의 활성을 감소시킴으로써 혈소판응집을 억제시키는 것으로 나타났으며, 혈액응고인자중 thrombin뿐만이 아니라 내인성경로의 factor VII, IX, XI, XII의 활성 또한 억제 하였다. 그러나 CV-40-Va-1의 항응고 활성은 thromin에 직접 작용하는 것이 아니라 antithrombin III 의존적 활성을 보였다. Sulfation에 의하여 CV-40-Va-1의 항응고활성의 증가와 다당의 desulfation시 상반된 결과에서 CV-40-Va-1의 황산기가 항응고활성의 중요한 인자임을 알 수 있었다. CV-40-Va-1을 TFA로 부분가수분해하여 얻은 획분들(Fr.I, Fr.II)에서는 항응고 활성이 감소하였으나 분자량 1,000정도로 추정되는 획분(Fr.II)은 오히려 혈소판응집을 강력하게 억제하였다.

• Archives of Pharmacal Research
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• 제26권6호
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• pp.441-445
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• 2003

New sulfonated amino ribofuranans were synthesized to elucidate the relationship between structure and specific biological activities such as anti-HIV and blood anticoagulant activities. The synthesis was performed by sulfonation of copolymers having various proportion of (1$\rightarrow5)-\alpha$-D-ribofuranosidic unit. The sulfonation with piperidine N-sulfonic acid produced the sulfonated amino ribofuranans in high yield. The anti-HIV activity of sulfonated 3-amino-3-deoxy-(1$\rightarrow5)-\alpha$-D-ribofuranan showed more potent by increasing the degree of sulfonation and the average molecular weights. This activity was almost equal to the activities of sulfonated ribofuranans and ribopyranans reported before in spite of low molecular weight. The blood anticoagulant activities was observed at 36-48 mg/units, more potent than standard dextran sulfonate, 22.7 mg/units. In addition, the blood anticoagulant activities of sulfamide-copolysaccharide consisting various proportion of (1$\rightarrow5)-\alpha$-D-ribofuranan units were potentiated by increasing sulfonated amino-ribofuranan units from 13 to 21 mg/units.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.216.2-216.2
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• 2003

We previously reported that acharan sulfate from the African giant snail Achatina futica showed the anticoagulant activity in vitro, but it was much less than that of heparin. In present study, the anticoagulant activity of acharan sulfate was investigated in vivo. Intravenous administration of acharan sulfate prolonged the clotting time (APTT) in mice and rats in a dose-dependent manner. (omitted)

• 한국식품영양과학회지
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• 제29권2호
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• pp.335-341
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• 2000

허브를 비롯한 식용되는 채소류로부터 항응고 활성을 검색하기 위하여 93종을 대상으로 냉수(Fr. I), 메탄올(Fr. ll), 열수(Fr. lll)추출물을 각각 조제하였다. 내인성 경로에 작용하는 항응고 활성은 수용성 획분인 Fr. I과 Fr.lll를 대상으로 activated partial thromboplastin time(APTT)으로 검색한 결과 양파, 마늘, 정향, 쑥, 울금 등이 높은 활성을 보였으며, 외인성 경로와 공통경로에 작용하는 항응고 활성은 저분자임을 감안하여 Fr. I과 Fr. II를 대상으로 각각 prothrombin time(PT) 과 thrombin time(TT)으로 검색한 결과 민트, 이탈리안 시즈닝, 로즈메리, 타라곤, 울금, 백리향, 와사비는 공통경로에 항응고 활성을 나타내였으나 외인성 경로에 단독으로 항응고 활성을 나타내는 시료는 없었다. 1, 2차 검색 결과 가장 높은 항응고 활성을 보인 정향(Eugenia caryophyllate, clove)을 대상으로 산지를 달리하여 항응고 활성을 검색한 결과 홀랜드산 정향의 활성이 가장 높았다.

• 한국식품영양과학회지
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• 제31권5호
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• pp.917-923
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• 2002

청각에서 분리된 항응고 다당류의 혈액응고 저해기작을 검토하였다. 항응고성 다당 획분(CF-30 IV-ii, CF-30-IV)은 내인성 경로와 공통 경로에서 농도 의존적으로 작용한다. 항응고획분(CF -30-IV-ii)은 내인성 경로의 factor asaay시 lupus an ticoagulant 항체의 활성 에 영 향을 주지 않았으나 응고과정 중 factor Ⅷ, Ⅸ, \ulcorner, \ulcorner의 활성을 저해하였다. CF-30-IV-4-ii는 농도의 존적으로 fibrine을 생성시키지 않음으로써 thrombin에 직접 작용하지 않는 antithrombin m의존적 항응고 활성 기작을 보였다. 청각의 항응고 활성은factor assay와thrum bin의 저해 양식을 고려해볼 때 antithrombin III의 활성을 증대시켜 혈액응고 인자 중 serine proteinase의 활성을 저해함으로써 항응고 활성을 나타내는 물질로 판명되었다. CF-30-IV획분의 in vivo 활성을 측정한 결과 꼬리정 맥주사에 의해 150 mg/kg의 농도로 마우스에 투여시 thrombin에 대한 100%의 항치사성 효과를 나타내었다 또한 CF-30-IV를 마우스의 꼬리 정맥에 주입하고 혈액을 채취 ex vivo상에서 항응고 활성을 측정한 결과, 생체내에서 100mg1kg의 농도까지도 시료량에 의존하는 항응고 활성을 보였다

• Archives of Pharmacal Research
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• 제24권2호
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• pp.109-113
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• 2001

Curdlan is a natural $\beta$-1,3-glucan produced by Agrobacterium biovar 1. In this study, the anticoagulant activity of sulfoalkyl derivatives of curdlan was investigated by carrying out activated partial thromboplastin time (APTT) assay and compared with that of o-sulfonated curdlan. Approximately 100-fold higher concentration of o-sulfonated curdlan than heparin was required to obtain the same level of the clotting time. Anticoagulant activity of curdlan derivatives was dependent on the degree of sulfation in prolonging the clotting time. However, the chain length of the substituent did not play a role in prolonging the clotting time. The curdlan derivatives enhanced thrombin inhibition by mediating through antithrombin III. The inhibition of thrombin by o-sulfonated curdlan was found to be approximately 10-fold weaker than that by heparin.