• 생약학회지
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• 제26권2호
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• pp.139-147
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• 1995

Crinum asiaticum var. japonicum is a wild plant growing only in Jeju-island, Korea, and in Japan. The whole part of this plant has been known to have the pharmacological actions such as analgesic, anti-inflammatory, platelet-aggregation inhibitory, antitussive, and expectorant. With these assumed actions, the leaves (Crinum folium) of this plant has been used in the folk remedies for arthritis and arthralgia. There is, however, no scientific evidences for the pharmacological actions of Crinum asiaticum var. japonicum. In the present study, the analgesic, anti-inflammatory, and platelet-aggregation inhibitory actions of Crinium folium were evaluated using writhing test, tail-flick test, carrageenin antiedema test, in vitro thromboxane $B_2$ quantitation assay and in vitro platelet aggregation test. In order to obtain the partially purified fraction whose pharmacological action is excellent, the methanol extract of Crinium folium was fractionated consecutively into four biological fractions such as ether, ethyl acetate, butanol, and water fractions and their pharmacological actions of the fractions were investigated. Putting our results together, Crinium folium, especially ethyl acetate fraction was proven to have significant analgesic, anti-inflammatory and platelet-aggregation inhibitory actions by inhibition of prostanoids biosynthesis as one of its mechanism of action.

• 대한임상검사과학회지
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• 제51권1호
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• pp.34-41
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• 2019

혈소판 응집은 혈관 손상의 경우 지혈 플러그 형성에 필수적이다. 그러나, 과도한 혈소판 응집은 혈전증, 죽상 동맥 경화증 및 심근 경색과 같은 순환기 장애를 일으킬 수도 있다. Scopoletin은 Scopolia 또는 Artemisia 속 식물의 뿌리에서 발견되는 성분으로, 항응고 및 항말라리아 작용을 가지는 것으로 알려져 있다. 본 연구는 collagen에 의해 유발된 혈소판 응집에 scopoletin이 미치는 영향을 조사하였다. Scopoletin은 활성화된 혈소판에서 생성되는 응집 유도 분자인 thromboxane $A_2$ ($TXA_2$) 및 세포 내 $Ca^{2+}$ 동원 ($[Ca^{2+}]_i$)의 하향 조절을 통해 항 혈소판 효과를 나타내었다. 한편, scopoletin은 세포 내 $Ca^{2+}$-길항제인 것으로 알려져 있는 cyclic adenosine monophosphate(cAMP)와 cyclic guanosine monophosphate (cGMP) 수치를 증가시켰다. 특히, scopoletin은 cGMP보다 cAMP 수준을 강력하게 증가함으로써 콜라겐에 의해 유발된 사람 혈소판 응집에서의 ${\alpha}IIb/{\beta}_3$에 대한 피브리노겐 결합을 억제하였다. 또한, scopoletin은 용량 의존적으로 collagen에 의해 증가된 adenosine trisphosphate (ATP)의 방출을 억제하였다. 이 결과는 혈소판 내 과립 분비를 통한 응집 증폭작용이 scopoletin에 의해 억제되었음을 의미한다. 따라서, 본 연구는 scopoletin이 강력한 항혈소판 효과를 가지며 혈소판-유래의 혈관 질환을 예방할 가능성이 크다는 것을 입증하였다.

• 약학회지
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• 제43권6호
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• pp.809-817
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• 1999

The effect of 2-(4-cyanophenyl)amino-1,4-naphthalenedione-3-pyridinium perchlorate (PQ5) on pla-telet aggregation and its action mechanisms were investigated with rat platelet. PQ5 inhibited the platelet aggregation induced by collagen ($6{\;}{\mu\textrm{g}}/ml$), thrombin (0.4 U/ml) and A23187 ($3{\mu}M$) in concentration-dependent manner with $IC_{50}$ values of 5.50, 25.89 and $37.12{\;}{\mu}M$, respectively. PQ5 also significantly reduced the thromboxane $A_2$ (TXA2) formation in a concentration dependent manner. The collagen-induced arachidonic acid (AA) release in [-3H]-AA incorporated platelet, an indication of the phospholipase $A_2$ activity, was decreased by PQ5 pretreatment PQ5 significantly inhibited the activity of thormboxane synthase only at high concentration ($100{\mu}M$), but did not affect the cyclooxygenase activity at all. Collagen-induced ATP release was significantly reduced by PQ5. Calcium-induced platelet aggregation experiment suggests that the elevation of intracellular free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) by collagen stimulation is decreased by the pretreatment of PQ5, which is due to the inhibition of calcium release from intracellular store and influx from outside of the cell. PQ5 did not showed the effect of anticoagulation as prothrombin time (PT) or activated partial thromboplastin time (APTT). Form these results, it is suggested that PQ5 exerts its antiplatelet activity through the inhibition of the intracellular $Ca^{2+}$ mobilization and the decrease of the $TXA_2$ synthesis.

• Journal of Nutrition and Health
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• 제37권3호
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• pp.182-192
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• 2004

Conjugated linoleic acid (CLA) is the mixture of positional and geometric isomers of linoleic acid (LA), which is found abundantly in dairy products and meats. This study was performed to investigate the anticarcinogenic effect of CLA in HepG2 hepatoma cells. HepG2 cell were treated with LA and CLA at the various concentrations of 10, 20, 40, 80 uM each at different incubation times. After each incubation times, cell proliferation, fatty acids incorporation into cell, peroxidation and postaglandin E$_2$ (PGE$_2$) and thromboxane $A_2$ (TXA$_2$) for the eicosanoid metabolism were measured. LA treated HepG2 cells were increased cell growth 6 - 70％ of control whereas CLA increased cell death the half of those in LA group (p 〈 0.001). LA and CLA were incorporated very well into the cellular membranes four times higher than in control according to concentration and longer incubation times. Moreover, LA synthesized significantly arachidonic acids corresponding with LA concentration compared to CLA supplementation. The supplementation with LA increased intracellular lipid peroxides concentration corresponding with LA concentration and five times higher than those in CLA significantly at any incubation times (p 〈 0.001). PGE$_2$ and TXA$_2$ levels were three to twenty times lower in condition of CLA treatments than LA, respectively. Overall, the dietary CLA might change the HepG2 cell growth by the changes of cell composition, production of lipid peroxide. Since CLA have not changed the levels of arachidonic acid of cell membrane, which was sources of eicosanoids, eicosanoid synthesis was not increased in CLA compared to LA. Our results was suggest CLA has a possibility to protect the progress of atherosclerosis because CLA does not produce lipid production and endothelial contraction factors in liver.

• Journal of Nutrition and Health
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• 제28권2호
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• pp.95-106
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• 1995

The effects of various n-6/n-3 ratios(about 2, 4, 6, 8) of dietary fatty acids on various lipid levels and prostaglandin production were studied at the constant P/S ratio (1.5-1.6) in young (5 weeks old) and adult(8 months old) Sprague-Dawley rats using palm oil, safflower oil and sardine oil. The concentration of serum cholesterol tended to increase with the increasing n-6/n-3 ratio. The tendency of HDL-cholesterol levels was similar to serum cholesterol levels. These were not apparent differences between young and adults rats. Serum triglyceride levels increased according to increasing n-6/n-3 ratio in young rats. These were generally high in the adult rats compared with the young rats. Though liver cholesterol level tended to increase according to the increasing n-6/n-3 ratio in the young rats. The liver triglyceride level did not change according to the n-6/n-3 ratio. However, these levels were apparently higher in the adult than in the young rats. The fatty acid compositions of phosphatidylcholine(PC) were similar in serum and liver. The arachidonate/linoleate ratios in tissue PC were influenced by the n-6/n-3 ratio. They tended to be lower in the adult rats compared with the young rats. It was suggested that the activity of $\Delta$6-desturase was decreased by aging. Production of platelet thromboxane A2(TXA2)and aortic prostacyclin(PGI2) was not apparently influenced with n-6/n-3 ratio. Whereas the ratio of TXA2/PGI2 was the lowest value at 3.8 of n-6/n-3 ratio, expecially in the young rats. Thus this ratio seemed to be a desirable level to protect atherosclerosis. These results indicate that the lipid level and prostaglandin production were influenced not only by n-6/n-3 ratio(under constant P/S ratio) but by aging, particulary triglycerde level and arachidonic/linoleic acid ratio.

• Journal of Nutrition and Health
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• 제26권7호
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• pp.829-838
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• 1993

This study was designed to compare the effect of different dietary fats on the incidence of colorectal tumor, the level of plasma thromboxane B2(TXB2) and fatty acid profiles of platelet and colonic mucosal lipids in N - methyl - N - nitro - N - nitrosoguanidine(MNNG) - treated rats. Male Sprague Dawley rats, at 8 weeks old, were divided into 2 groups and infused intrarectally with saline(control group) or with 2mg MNNG(carcinogen-treated group) twice a week for 3 weeks. Each group was again divided into 4 groups and fed one of four diets(BT, CO, PO, FO) containing dietary fat at 9%(w/w) level for 37 weeks, Dietary fats were beef tallow(7.2%)+corn oil(1.8%) for BT, corn oil(9.0%) for CO, perilla oil(9.0%) for PO, fish oil (6.5%)+corn oil (2.5%) for FO diets. MNNG-treated rats had colonic tumor, while no tumors(adenocarcinoma and adenoma) than others. Tumor sizes in BT-MNNG rats ranged from 2mm papillary form to 15mm of polypoid. However, the size of tumors in PO-MNNG or FO-MNNG rats could not be measured by gross examination. BT-MNNG and CO-MNNG groups were higher in the level of plasma TXB2 and the ratio of c20 : 4/c20 :5 platelet. PO-MNNG groups were lower in the ratio of c20 : 4/c20 : 5(p<0.05) in fatty acid of colonic mucosal lipids suggesting that perilla oil and fish oil could reduce the level of PGE2 and TXB2 by modifying its precursor content and restrain tumor promotion in colon. Effect of perilla oil rich in $\alpha$-linolenic acid on colon carcinogenesis was similar to that of fish oil and thus perilla oil could have a protective effect against colon cancer possibly by inhibiting the production of arachidonic acid metabolite.

• Korean Chemical Engineering Research
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• 제47권5호
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• pp.615-619
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• 2009

$Tr{\ddot{o}}ger$'s base 중 (+)-$Tr{\ddot{o}}ger$'s base는 항혈전제로 Thromboxane A2($T{\times}A2$) Synthase의 효소 활성을 저해하여 동맥경화의 치료제로 널리 사용되고 있다. 따라서 (+)-$Tr{\ddot{o}}ger$'s base를 라세미 혼합물로부터 순수하게 분리하는 것은 중요한 연구대상이다. 하지만 실험을 통한 (+)-$Tr{\ddot{o}}ger$'s base의 순수한 분리에는 많은 시간과 비용이 필요하게 되므로 분리 효율의 향상에 많은 어려움이 있다. 이러한 단점을 보완하고자 Aspen Chromatography 전산 모사는 여러 조건하에서 직접 실험을 하지 않는 효율적인 시뮬레이션 방법으로서 분리 효율 등을 예측할 수 있으므로 생산성 향상에 드는 시간과 비용을 절약할 수 있다. Aspen Chromatography simulator로 $Tr{\ddot{o}}ger$'s base의 주입량과 이동상 속도를 변화시켜 TB(-)와 TB(+)의 분리도, 수율 그리고 다양한 흡착식을 비교하였다. TB(-)와 TB(+)의 분리도와 순수한 수율은 이동상 속도 0.25 mL/min일 때 가장 높았다. 고정상과 이동상 농도사이의 관계식을 표시하는 등온흡착식을 변화하여 전산모사한 결과 Ideal Adsorbed Solution(IAS) Statistical Langmuir 등온흡착식이 분리 효율에 좋은 결과를 가져왔다.

• 한국식품위생안전성학회지
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• 제19권3호
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• pp.167-170
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• 2004

The present study was undertaken to investigate the effects of Moutan Cortex Radicis extracts and paeonol, a major component, on rabbit platelet aggregation and thromboxane (TX) $A_2$ formation. Moutan Cortex Radicis methanol and butanol layers (100 ${\mu}g/mL$) showed the weak inhibitions, and water layer (100 ${\mu}g/mL$) had no effect on the collagen-induced platelet aggregation. Whereas, hexane and EtOAc layers potently inhibited the collagen (3 ${\mu}g/mL$)-induced platelet aggregation with the $IC_{50}$ values of 10.9${\pm}$1.0 and 31.5${\pm}$0.8 ${\mu}g/mL$, respectively. Paeonol isolated from the hexane-acetone layer specifically inhibited the collagen-induced platelet aggregation with the $IC_{50}$ value of 113.1 ${\pm}$ 0.9 ${\mu}M$, whereas it had little effects on the other agonists such as AA-, thrombin-, A23187- and thapsigargin-induced platelet aggregations. Paeonol also potently inhibited the collagen-induced TXB formation in rabbit platelet in a concentration-dependent manner. These results suggest that paeonol may inhibit rabbit platelet aggregation by interfering with an essential step in collagen-induced platelet activation and $TXA_2$ formation. Paeonol may be a promising candidate for an antiplatelet agent.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.257-262
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• 2015

It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations ($10^{-5}{\sim}10^{-4}M$) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with $10^{-5}M$ hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with $10^{-5}M$ indomethacin (nonspecific cyclooxygenase inhibitor) and with $10^{-6}M$ NS-398 (selective cyclooxygenase inhibitor), but also with $10^{-6}M$ Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane $A_2$ synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane $A_2$, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

• Journal of Nutrition and Health
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• 제24권2호
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• pp.97-103
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• 1991

에탄올이 면역계의 항원전달세포이며, 동시에 감마인터페론 등의 림포카인에 의해 활성화되면 작동세포의 역활을 하는 단핵구-대식세포의 arachildonic acid 대사의 cyclooxygenasc 경로의 프로스타글라딘 생산에 미치는 영향을 연구하기 위하여 감마 인터페론으로 전처치하여 활성화시킨 단핵구와 대조군 단핵구를 사용하여 방사면역측정법으로 프로스타글라딘들을 측정하였다. 건강한 성인의 말초혈액으로 Ficoll-Hypaque용액을 이용한 농도구배법과 젤라틴 피복 플라스크를 이용하여 단핵구를 순수하게 분리한 다음 800단위의 감마 인터페론을 사용하여 3일동안 단핵구를 활성화시켰다. 감마인터페론으로 활성화 시키지 않은 $10^6$개의 단핵구에 100mM,300mM,600mM의 에탄올을 30분간 반응시킨 후 6시간후에 thromboxane B$_2$, PGEB$_2$ 와 6-keto-PGF1$\alpha$ 와 PGE$_2$ 모두 대조군에 비하여 생산이 증가하였다. 감마인터페론으로 전처치한 경우에는 알코올 처치에 관계없이 세가지 프로스타글란딘들 모두 6시간과 24시간에서 대조군보다 감소되었다. 이와같은 성적들로 미루어 볼 때 감마인터페론 처치가 에탄올로 유발한 단핵구 arachidonic acid 대사의 변화를 억제한다고 사료된다.