• 한국수산과학회지
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• 제45권4호
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• pp.303-306
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• 2012

Anti-angiogenesis therapy is one of the most promising strategies for the treatment of cancer. We investigated the anti-angiogenesis activity of an extract from the ark shell Scapharca subcrenata and attempted to purify the active compounds. The crude extract of the ark shell inhibited the proliferation of human vein endothelial cells (HUVEC-1) and tube formation by human dermal microvascular endothelial cells (HMEC-1). The methanol extract of the viscera of the ark shell showed activity. The ark shell extract acts as an angiogenesis inhibitor and could be developed further as a health substance, functional food, and anticancer agent.

• 동의생리병리학회지
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• 제29권6호
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• pp.485-491
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• 2015

This study was aimed to investigate the relaxation effects of Eucomiae Cortex (EC) extract in isolated rabbit corpus cavernosum smooth muscle and its mechanism. To evaluate the relaxation of EC extract in rabbit corpus cavernosum, EC extract was treated in corporal strips which were precontracted with phenylephrine(PE). To study its mechanism, Nω-nitro-L-arginine (L-NNA) was pretreated after infuse of EC extract and compared with non-treated. In calcium chloride (Ca²⁺) -free krebs solution, EC extract and Ca²⁺ 1 mM were infused by turns after Ca²⁺ 1 mM was treated into corporal strips contracted by PE. Cell ability, nitric oxide (NO) and epithelial nitric oxide synthase (eNOS) on human umbilical vein endothelial cell (HUVEC) were measured by MTT assay, Griess reagent system and histochemical, immunohistochemical methods. EC extract showed a significant relaxation effects on the corporal strips, this effects were inhibited by pretreatment of L-NNA. EC extract inhibited the increase of contraction by Ca²⁺ influx in Ca²⁺-free krebs solution, and eNOS positive reaction in corpus cavernosum, NO production in HUVEC increased by treatment of EC extract. These result suggest that the relaxation effects of EC extract in isolated corpus cavernosum smooth muscle are involved in increase of eNOS and NO production, blocking of extracellular Ca²⁺ influx.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.92-92
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• 1995

It has been suggested that oxygen-derived free radicals have an important role in the pathophysiology of acute gastric ulceration induced by NSAIDs and ischemia-reperfusion. Taurine is hypothetized to exert its protective effect on NSAIDS-induced gastric injury by its antioxidant properties, Protect ive effect of taurine on indomethacin-induced gastric mucosal lesion and its protective mechanism were investigated. Intragastric administration of 25 mg/kg of indomethacin induced hemorrhagic lesions on the glandular stomach in rats, Pretreatment with 0.25 g/kg of taurine for 3 days significantly reduced the gastric lesion formation and Inhibited the elevation of lipid peroxide level In gastric mucosa. Both resting and FMLP-induced luminol-dependent chemiluminescence of rat peritoneal neutrophils increased immediately after treatment of indomethacin. 5-20mM of taurine inhibited chemiluminescence of neutrophils activated by indomethacin and/or FMLP. Human neutrophils (polymorphonuclear leukocytes) significantly adhered to confluent monolayer of human umbilical vein endothelial cells(HUVEC) after coincubation with aspirin or indomethacin. Also taurine prevented neutrophil adhesion induced by these drugs to HUVEC in dose-dependent manner. These results indicate that the protective effect of taurine against NSAIDS-induced gastric mucosal Injury is due to its antioxidant effect, which inhibits lipid peroxidation and neutrophil activation.

• Archives of Pharmacal Research
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• 제19권2호
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• pp.85-90
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• 1996

It has been suggested that oxygen-derived free radicals play an important role in the pathophysiology of acute gastric ulceration induced by NSAIDs and ischemia-reperfusion. Taurine is hypothetized to exert its protective effect on NSAIDs-induced gastric injury by its antioxidant properties. Protective effect of taurine on indomethacin-induced gastric mucosal lesion and its protection mechanism were investigated. Intragastric administration of 25 mg/kg of indomethacin induced hemorrhagic lesions on the glandular stomach in rats. Pretreatment with 0.25 or 0.5 g/kg of taurine one day before or for 3 days significantly reduced the gastric lesion formation and inhibited the elevation of lipid peroxide level in gastric mucosa. The luminol-dependent chemiluminescence of rat peritoneal neutrophils increased immediately after treatment of FMLP or indomethacin. Taurine (5-20 mM) inhibited chemiluminescence of neutrophils activated by FMLP. Human neutrophils (polymorphonuclear leukocytes) significantly adhered to the confluent monolayer of human umbilical vein endothelial cells (HUVEC) after coincubation with indomethacin. This neutrophil adhesion induced by indomethacin to HUVEC was prevented by taurine in a dose-dependent manner. These results indicate that the protective effect of taurine against NSAIDs-induced gastric mucosal injury is due to its antioxidant effect, which inhibits lipid peroxidation and neutrophil activation.

• Molecules and Cells
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• 제39권4호
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• pp.292-298
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• 2016

Aquaporin 1 (AQP1) is expressed in most microvasculature endothelial cells and forms water channels that play major roles in a variety of physiologic processes. This study aimed to delineate the transcriptional regulation of AQP1 by Mef2c in endothelial cells. Mef2c cooperated with Sp1 to activate human AQP1 transcription by binding to its proximal promoter in human umbilical cord vein endothelial cells (HUVEC). Over-expression of Mef2c, Sp1, or Mef2c/Sp1 increased HUVEC migration and tube-forming ability, which can be abolished AQP1 knockdown. These data indicate that AQP1 is a direct target of Mef2c in regulating angiogenesis and vasculogenesis of endothelial cells.

• Clinical and Experimental Pediatrics
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• 제50권12호
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• pp.1194-1199
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• 2007

목 적 : 본 연구자들은 전자간증, 부당 경량아, 자궁 내 발육지연 등의 질환들이 공통적으로 혈관내피세포의 기능 변화와 어느 정도 관련되어 있을 것으로 추론하였다. 따라서 전자간증 산모의 신생아, 부당 경량아의 제대혈관내피세포를 배양하여 제대의 혈관내피세포에서 발현되는 대표적인 혈관 수축작용 물질인 endothelin-1의 양을 측정한 후 정상 신생아 제대혈관 내피세포의 결과와 비교하여 각 질환에서 태아의 혈관내피세포의 endothelin-1 발현 기능에 어떤 차이가 있는지를 확인하고, 또한 배양된 정상아 제대혈관내피세포에 전자간증 산모의 신생아와 부당 경량아 및 정상아의 제대혈 혈청을 투여하여 발현된 endothelin-1의 양을 비교하여 혈청 내에 endothelin-1의 발현을 촉진시키는 인자가 있는지를 알아보았다. 방 법 : 전자간증으로 진단 받은 산모의 신생아를 전자간증군(n=7), 부당 경량아로 진단받은 신생아를 부당 경량아군(n=8), 정상 신생아를 정상군(n=12)으로 나누었다. 각 그룹에서 태어난 신생아 제대와 제대혈을 모아 제대혈은 그 혈청을 영하 $70^{\circ}C$ 이하에 보관하였다. 전자간증군, 부당 경량아군 및 정상군 신생아의 제대 혈관내피세포를 분리하고 배양하였다. 배양된 각각의 제대 혈관내피세포의 상층액에서 endothelin-1 level을 측정하였다. 다음에는 전자간증군, SGA군 및 정상군의 제대혈 혈장과 정상 신생아 제대 혈관내피세포를 함께 부양하여 그 상층액에서 endothelin-1 level을 측정하였다. 결 과 : 전자간증군, 부당 경량아군 및 정상군의 제대혈관내피세포를 배양하여 발현된 endothelin-1의 양을 측정한 결과 전자간증군과 SGA군의 제대혈관내피세포의 endothelin-1 발현은 정상군과 유의한 차이가 없었다. 그러나 배양된 정상아 제대혈관내피세포에 전자간증군과 SGA군의 제대혈 혈청을 투여하여 발현된 endothelin-1의 양은 정상군에 비하여 유의하게 증가되었다. 결 론 : 전자간증 신생아나 부당 경량아의 혈관내피세포의 기능이상을 유발하는 인자가 전자간증과 부당경량아 제대 혈청내에 존재할 가능성이 있을 것으로 생각된다.

• 한국식품과학회지
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• 제42권2호
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• pp.210-216
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• 2010

혈당강하 효과가 있다고 알려진 해당근 추출물을 이용하여 AGEs 생성 저해에 따른 초기 동맥경화증에 대한 효과에 대하여 검토하였다. 먼저 해당근 추출물이 AGEs에 의하여 생성이 촉진된 ROS를 제거하는 효과가 있는지를 확인하기 위하여 항산화 활성을 측정하였다. 총 플라보노이드 함량을 측정한 결과 해당근의 메탄올 추출물은 $128.1{\pm}2.0\;{\mu}g$ quercetin equivalents(QE)/mg DM,총 폴리페놀 함량은 $345.2{\pm}5.7\;{\mu}g$ gallic acid equivalents(GAE)/mg DM으로 나타났다. 환원력 측정을 위한 FRAP assay는 $2.19{\pm}0.1\;mM$ $FeSO_4{\cdot}7H_2O$/mg DM으로 $25.5{\pm}0.3$ $FeSO_4{\cdot}7H_2O$/mg DM 인 ascorbic acid에 비해 약 9% 정도의 환원력을 가지고 있었으며, 전자공여능의 경우 $DPPHSC_{50}$값이 $34.2{\pm}0.1\;{\mu}g$ DM/mL로 대조군인 ascorbic acid의 $6.8{\pm}0.1\;{\mu}g$ DM/mL과 비교하여 약 20% 정도의 높은 항산화력을 갖고 있었다. 또한, HPLC 분석을 통해 해당근 생물 100 g을 기준으로 240 mg의 EGCG와 50 mg의 kaempferol을 함유하는 것으로 나타났다. AGEs에 의해 유도된 HUVEC의 ROS 생성 저해 효과는 해당근 추출물 100, $500\;{\mu}g/mL$ 처리 시 각각 63, 77%로 나타났다. 또한, monocyte adherent assay에서 해당근 추출물은 $100\;{\mu}g/mL$ 처리시 정상을 0%로 하였을 때 AGEs에 의해 유도된 단핵구 부착을 33%, $500\;{\mu}g/mL$ 처리시 약 75% 정도로 농도 의존적으로 부착을 저해하는 것을 관찰할 수 있었으며, 유도되지 않은 HUVEC의 저항은 $113{\Omega}{\cdot}cm^2$ 에서 glycer-AGEs 처리 시 $88{\Omega}{\cdot}cm^2$로 낮아진 것을 해당근 추출물을 $100\;{\mu}g/mL$ 처리 시 약 $102{\Omega}{\cdot}cm^2$, $500\;{\mu}g/mL$ 처리시 약 $106{\Omega}{\cdot}cm^2$로 저항의 감소를 억제하는 것을 관찰할 수 있었다.

• 동의생리병리학회지
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• 제27권4호
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• pp.400-408
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• 2013

This study aimed to investigate the relaxation effects and its underlying mechanisms of Rubus coreanus(RC) extract in contracted rabbit corpus cavernous tissues by phenylephrine(PE) $1{\mu}M$. In order to define the relaxation effects of RC, rabbit corpus cavernous tissues were prepared in $2{\times}2{\times}6mm$ sized strip. The dose-dependent relaxation responses of RC at 0.01-3.0 $mg/m{\ell}$ in contracted strips induced by PE were measured and also observed after endothelial denudation. To analyze the underlying mechanisms of RC-induced relaxation, indomethacin(IM), tetraethylammonium chloride(TEA), $N{\omega}$-nitro-L-arginine (L-NNA), methylene blue(MB) were treated before RC extract infused into precontracted strips induced by PE. To study the effect of RC extract on influx of extracellular $Ca^{2+}$ in corpus cavernous strips, calcium chloride(Ca) 1 mM infused into precontracted strips induced by PE after pretreatment of RC extract in $Ca^{2+}$-free krebs-ringer solution. To investigate cytotoxic activity and nitric oxide(NO) concentration of RC extract on human umbilical vein endothelial cell(HUVEC), cell viability on HUVEC was measured by MTT assay, and NO concentration was measured by Griess reagent system. The cavernous strips were significantly relaxed by RC extract at 1.0 $mg/m{\ell}$, 3.0 $mg/m{\ell}$ and the relaxation responses to RC were inhibited significantly by endothelial disruption. The pretreatment of IM, TEA didn't affect RC extract-induced endothelium-dependent relaxation, but the pretreatment of L-NNA, MB reduced RC extract-induced endothelium-dependent relaxation. When $Ca^{2+}$ was supplied the cavernous strips which were precontracted by PE in a $Ca^{2+}$-free krebs-ringer solution, contraction of strips was increased, but pretreatment of RC inhibited contractile response to $Ca^{2+}$. When RC extract was applicated on HUVEC, NO concentration was increased. Our findings show that RC extract exerts a relaxing effect on corpus cavernosum in part by suppressing influx of extracellular $Ca^{2+}$ through activating the NO-cGMP system.

• 동아시아식생활학회지
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• 제24권3호
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• pp.351-358
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• 2014

본 연구에서는 호박씨유의 성분 특성과 기능성의 기초 자료 확보를 위해 수행되었다 그 결과, 호박씨유는 알려진 바와 같이 linoleic acid(44.7%), oleic acid(25.3%), palmitic acid(17.4%), stearic acid(7.9%)가 분석되었으며, 미량의 arachidonic acid(0.4%) 또한 함유하고 있었다. 세포 독성 실험을 통해 0.2 mg/mL 농도까지 독성이 관찰되지 않았고, 그 이상의 농도에서도 호박씨유보다는 용매에 의한 독성이 관찰되었다. 지방 성분 분석을 통해 구성 성분 및 함유량이 확인된 호박씨유를 이용하여 혈관 보호 및 질병 예방에 대한 잠재적 기능성을 연구하기 위해 nitric oxide 분비량 측정, 대표적인 세포 부착 단백질인 ICAM-1 및 VCAM-1의 발현과 cell proliferation 측정한 결과, 호박씨유는 TNF-${\alpha}$에 의해 감소된 nitric oxide를 유의하게 증가시켰다. 또한 ICAM-1과 VCAM-1의 발현을 확인한 결과, ICAM-1은 유의한 수준으로 감소되었고, 반면 VCAM-1은 감소하는 경향은 보였으나, 통계적인 유의성은 관찰되지 않았다. 호박씨유의 HUVEC proliferation 억제 효과는 TNF-${\alpha}$ 100 ng/mL 처리군(113%)과 비교하여 PSO 0.01 mg/mL, 0.05 mg/mL 및 0.1 mg/mL를 처리 군에서 100.7%, 100.8%, 90.3%의 억제 효과가 관찰되어 무처리 control군과 유사한 수준을 유지하는 것으로 관찰되었다. 위의 연구 결과를 종합해 보면, 호박씨유는 불포화지방산이 다량 함유된 우수한 식물성 유지이며, 기능적으로 혈관 보호 및 질병 예방에 잠재적으로 우수한 활성이 있음을 확인할 수 있었다. 따라서 본 연구 결과를 기초 자료로 하여 효과적인 기능성 식품 및 소재의 개발이 가능할 것으로 판단된다.

• 동의생리병리학회지
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• 제20권4호
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• pp.825-829
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• 2006

Rhus verniciflua Stokes has been used for treatment of blood stasis and abdominal mass in Oriental medicine. Rhus verniciflua Stokes has been experimentally reported to exert antioxidant, antiproliferative, antithrombotic and apoptotic activities. In the present study, the antiangiogenic and in vivo antitumor activities of aqueous extract of processed Rhus verniciflua Stokes (Nexia) by heat were examined to elucidate its anticancer mechanism. Nexia showed weak cytotoxiicty against human umbilical vein endothelial cells (HUVEC) and Lewis lung carcinoma cells (LLC) with IC50 of${\sim}200\;{\mu}g/ml\;and\;>200\;{\mu}g/ml$, respectively. Nexia significantly inhibited the proliferation and migratory activity in vascular endothelial growth factor(VEGF) treated HUVEC. Furthermore, Nexia effectively suppressed the tumor volume in A549 nonsmall lung cancer bearing athymic nude mice, CanN. Cg-Foxn 1nu/CrljBgi up to 40.7% as well as tumor weight incised from LLC cells innoculated into the flank of C57BL/6 mice up to -50% compared with untreated control at a dose of 300 mg/kg. Taken together, these results suggest that processed Rhus verniciflua Stokes may inhibit the growth of Lewis lung carcinoma cells partly via inhibition of angiogenesis and can be potently applied to angiogenesis dependent cancers. However, it still needs a further research on molecular mechanism, angiogenesis animal study and clinical trial in future.