• Title/Summary/Keyword: anti-platelet effect

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Purification and Characterization of a new anti-coagulant protein, PP27, of placenta protein (annexinⅤ-like protein) (새로운 인간(人間) 태반(胎盤)유래의 항응고(抗凝固) 단백질(蛋白質) PP27 (annexin Ⅴ형(型) 단백질(蛋白質))의 정제(精製)와 특성(特性))

  • Kim Jang-Hyun
    • The Journal of Pediatrics of Korean Medicine
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    • v.14 no.2
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    • pp.33-46
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    • 2000
  • It has long been known that Jahage(紫河車) extracts of Placenta hominis are effective for immunological and vascular diseases in human body and thus, was used a major constituent of traditional oriental medicines. From full-term human placenta, we have purified a new type anticoagulant protein, PP27, using different chromatographic techniques of a phenyl TSK gel 650M column, DEAE, HA and Mono-Q columns. PP27 showed single band on SDS-PAGE with a molecular mass (Mr) of 27 kDa under denaturing conditions and a calibrated Sepharose 4B column chromatography indicated a molecular mass of 23 kDa, indicating that the value is similar to those of other PP4 enzyme reported to date. Isoelectric point of PP27 was p15.2. The protein was found to inhibit the coagulation time in a concentration-dependent manner. PP27 was acted as a vascular anticoagulant of annexin type, inhibits the blood clotting process by binding of the essential lipids in a reaction which is dependent on $Ca2^+$ ions. In the presence of $Ca2^+$ ions, PP27 combines with platelet membranes neutralizing their procoagulant effect. Coagulation triggered by the addition of thromboplastin/ lipid- mixtures is extinguished by PP27.

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Inhibitory Effects of YP 12, A Newly Synthesized Obovatol Derivative on Rat Aortic Vascular Smooth Muscle Cell Proliferation

  • Lim, Yong;Lee, Mi-Yea;Jung, Jae-Kyung;Pyo, Myoung-Yun;Yun, Yeo-Pyo
    • Journal of Food Hygiene and Safety
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    • v.26 no.3
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    • pp.187-191
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    • 2011
  • Platelet derived growth factor (PDGF)-BB is one of the most potent vascular smooth muscle cell(VSMC) proliferative factors, and abnormal VSMC proliferation by PDGF-BB plays an important role in the development and progression of atherosclerosis. The aim of this study was to assess the effect of YP 12, a newly synthesized obovatol derivative, on the proliferation of PDGF-BB-stimulated rat aortic VSMCs. The anti-proliferative effects of YP 12 on rat aortic VSMCs were examined by direct cell counting and by using $[^3H]$ thymidine incorporation assays. It was found that YP 12 potently inhibited the growth of VSMCs. The pre-incubation of YP 12 (1-4 ${\mu}M$) significantly inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated rat aortic VSMCs in a concentration-dependent manner. In accordance with these findings, YP 12 revealed blocking of the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Whereas, YP 12 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. These results also show that YP 12 may have potential as an anti-proliferative agent for the treatment of restenosis and atherosclerosis.

Anti-Proliferative Activity of OD78 Is Mediated through Cell Cycle Progression by Upregulation p27kip1 in Rat Aortic Vascular Smooth Muscle Cells

  • Tudev, Munkhtsetseg;Lim, Yong;Park, Eun-Seok;Kim, Won-Sik;Lim, Il-Ho;Kwak, Jae-Hwan;Jung, Jae-Kyung;Hong, Jin-Tae;Yoo, Hwan-Soo;Lee, Mi-Yea;Pyo, Myoung-Yun;Yun, Yeo-Pyo
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.187-194
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    • 2011
  • Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [$^3H$]-thymidine incorporation assays. Treatment with 1-4 ${\mu}M$ OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the $G_0/G_1$ to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) $p27^{kip1}$. However, OD78 did not affect the CKI $p21^{cip1}$ or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BB-induced RASMC proliferation by perturbing cell cycle progression, potentially through $p27^{kip1}$ pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

Experimental Effects of Mahwangkanghwal-tang(Mahuangqianghuo-tang) on the Adjuvant Arthritis in Rats (마황강활탕(麻黃羌活湯)이 Adjuvant 관절염에 미치는 실험적 효과)

  • Sul, Jae-Uk;Shin, Mi-Suk;Choi, Jin-Bong
    • Journal of Korean Medicine Rehabilitation
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    • v.15 no.2
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    • pp.55-65
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    • 2005
  • Objectives : Mahwangkanghwal-tang(Mahuangqianghuo-tang;MKT) is a prescription that treat clinically arthritis. The purpose of this study is to investigate effects of MKT extract on the adjuvant arthritis in pathological rats induced by Freund's complete adjvant($0.2m{\ell}/kg$). Methods : Experimental groups were divided into 4 groups ; Normal group were administered DDW $1.0m{\ell}$ to normal rats for 14 days, Control group were administered DDW $1.0m{\ell}$ to arthritic rats for 14 days, Sample A group were administered MKT $300m{\ell}/kg$ $1.0m{\ell}$ to arthritic rats for 14 days, Sample B group were administered MKT $500m{\ell}/kg$ $1.0m{\ell}$ to arthritic rats for 14 days. The present author observed body weight, inhibitory effect of edema, analgesic effects by hot plate, WBC, RBC, hemoglobin, hematocrit, platelet, total serum protein level and total serum cholesterol level. Results : 1. All sample group were increased body weight compared with control group, sample B group were significantly increased body weighty compared with control group. 2. All sample group significantly inhibited the rated of paw edema compared with control group. 3. All sample group significantly prolongated the escaping time compared with control group, sample B group significantly prolongated the paw licking time compared with control group. 4. All sample group were significantly decreased WBC compared with control group, sample B group were significantly decreased RBC compared with control group. 5. All sample group ware decreased hemoglobin and hematocrit compared with control group. 6. All sample group ware increased total serum cholesterol compared with control group, sample B group were significantly decreased platelet compared with control group. 7. All sample group ware significantly decreased total serum protein level compared with control group. 8. All sample group ware increased total serum cholesterol compared with control group, sample B group were significantly increased total serum cholesterol level compared with control group. Conclusions : We thought that Mahwangkanghwal-tang(Mahuangqianghuo-tang) could be used for curing rheumatoid arthritis, anti-inflammatory effect was somewhat better in much than small dosage.

The Effect of Ishige okamurae Extracts on Antioxidant Activity and Serum Lipid Content in Ovariectomized Rats (패 추출물의 항산화 활성 및 난소절제 흰쥐의 혈중 지질 함량 변화에 미치는 영향)

  • Kim, Bokyung;Kim, Mihyang
    • Journal of Life Science
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    • v.23 no.12
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    • pp.1501-1508
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    • 2013
  • This study investigated antioxidant activity and the lipid content of serum for the possible outcome of improving the activity of Ishige okamurae extracts in ovariectomized rats. The antioxidant effects of an Ishige okamurae water extract and an Ishige okamurae ethanol extract were measured by evaluating DPPH free radical scavenging activity and SOD-like activity. Fifty, seven-week old female Sprague Dawley rats were randomly assigned to five groups as follows: sham-operated rats (SHAM), ovariectomized rats (OVX-CON), ovariectomized rats that were treated with 17-beta-estradiol (200 ${\mu}g/kg/day$), and ovariectomized rats that were treated with Ishige okamurae extracts (50 mg/kg/day and 200 mg/kg/day, respectively). The diets were fed to the rats for seven weeks after ovariectomy. The antioxidant activities of the water and ethanol extracts of Ishige okamurae increased in a dose-dependent manner, and the ethanol extract was found to be higher than the water extract. Therefore, we examined the effect of an Ishige okamurae ethanol extract on total serum cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol levels, and anti-platelet aggregation. The total-cholesterol and triglyceride content of the serum increased in the OVX-CON group compared to the SHAM group, but supplementation with the Ishige okamurae ethanol extract caused these factors to decrease. Notably, the serum LDL-cholesterol concentration in the supplemented 200 mg/kg/day Ishige okamurae ethanol extract group was significantly more reduced than it was in the OVX-CON group. In addition, the platelet aggregation ability was lower in the groups treated with Ishige okamurae than it was in the OVX-CON group. According to these results, the effects of Ishige okamurae extract on serum lipid content in ovariectomized rats were illuminated.

Anti-Myelosuppression Effects of Korean Red Ginseng in SD Rat Injected with 5-fluorouracil

  • Park, Hye-Jung;Han, Jong-Min;Kim, Hyeong-Geug;Choi, Min-Kyung;Lee, Jin-Seok;Son, Chang-Gue
    • The Journal of Korean Medicine
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    • v.33 no.2
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    • pp.47-55
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    • 2012
  • Objectives: This study aimed to investigate the preventive effect of red ginseng (RG) on 5-fluorouracil (5-FU)-induced side effects focusing on myelosuppression. Methods: Rats (n = 50) were divided into five groups, nave, control (ip, 5-FU injection of 150 mg/kg), and RG pre-treatment (po, 25, 50 and 100 mg/kg for 5 days before 5-FU injection). On the $7^{th}$ day after 5-FU injection, we evaluated the effects using peripheral hematological parameters, colony-forming assay, cytokine levels and histopathological finding. Results: The peripheral white blood cell and the differential count were dramatically suppressed by 5-FU, while RG (50 and 100 mg/kg) treatment significantly improved total white blood cell, neutrophil, lymphocyte and platelet counts. Also, RG (100 mg/kg) pre-treatment significantly increased the number of CFU-GM colony compared with the control group. RG pre-treatment also ameliorated the histopathological damage in bone marrow, spleen, stomach and small intestine tissue. Conclusions: These results demonstrate that Korean RG has preventive effects against 5-FU-induced myelotoxicity and gastrointestinal damage.

Preventive Effects of Aspirin on Cardiovascular Complications in Prostate Cancer Cases after Endocrinotherapy

  • Li, Xiao-Xia;Zhang, Yong-Gang;Wang, Dong;Chen, Yun-Fang;Shan, Yan-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4909-4913
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    • 2015
  • Objective: To explore the preventive effect of aspirin on the cardiovascular complications in prostate cancer after endocrinotherapy. Materials and Methods: A total of 92 patients with prostate cancer were divided into observation group (n=44) and control group (n=48). The control group was treated with medical castration plus anti-androgenic drugs. Based on the above treatment, the observation group was added aspirin. The follow-up duration was 2 years. The changes of partial prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation rate (PAG), prostate-specific antigen (PSA) and serum testosterone (T) before and after treatment as well as incidence of cardiovascular disease were observed. Results: The 2-year survival rates of patients without cardiovascular disease in observation group and control group were 95.45% (42/44) and 72.92% (35/48), respectively, and significant difference was presented between two groups by comparison to the survival rates ($x^2=8.5453$, p=0.0035). There was no statistical significance between two groups as well as before and after treatment regarding PT (p>0.05). After treatment, APTT went down and PAG was gradually on the rise in control group, while PAG down and APTT on the rise increasingly in observation group. Significant differences were presented between two groups as well as before and after treatment (p<0.01). Both PSA and T levels were decreased significantly in two groups after treatment (p<0.01), but there was no statistical significant between two groups (p>0.05). Conclusions: Application of endocrinotherapy in prostate cancer can easily lead to occurrence of cardiovascular disease, but cardiovascular complications can be prevented by aspirin, without affecting the effect of endocrinotherapy.

Bibliographic Study on the Moschus used to Acute Stage of Stroke (중풍급성기(中風急性期)에 활용(活用)되는 사향(麝香)에 관(關)한 문헌적(文獻的) 고찰(考察))

  • Huh, Jae-Hyeok;Kim, Sae-Gil;An, Ill-Hoe;Shin, Sun-Ho;Moon, Byung-Soon;Sung, Gang-Kyung
    • The Journal of Korean Medicine
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    • v.16 no.2 s.30
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    • pp.100-114
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    • 1995
  • This bibliographic study was designed to research indications of the Moschus which was representatively used for resuscitation in acute stage of stroke throughout successive books of oriental medicine. Especially, in this study, severe cases with disturbance of consciousness and acute stage of stroke were investigated. The results were summarized as the followings: 1. The Moschus was dried material which secreted from aromatic vescicle of Moschus moschiferus L.. which was pungent in flavor, warm in nature, nontoxic and strongly aromatic. The Moschus removed the obstruction in the channels and used to early stage of stroke. 2. The Moschus was aromatic resuscitatable medicine, which recovered disturbance of consciousness due to stroke. 3. The Moschus had excitatory actions of respirtory center and vascular motor center, heart stimulating action, inhibitatory action of the platelet aggregation and anti thrombin action and recovered cerebral ischemic change. According to these actions, the Moschus could be used cerebral infarction. 4. Prescriptions included the Moschus was used to symptoms of unconsciousness, secretion, stuporous mental state, dysarthria, facial palsy and hemiplegia. That was Angungwoohwangh wan(安宮牛黃丸), Woohwangchungshimwon(牛黃淸心元), Sahyangsohaphangwon(麝香蘇合香元), etc. According to the above mentioned results, the Moschus was aromatic resuscitatable medicine which was used for symptoms of conscius disturbance, convulsion, sudden fainting etc., promoted cerebral blood flow and had good effect on acute stage of stroke and severe cases with conscious disturbance. Therefore, it is considered that the Moschus must be studied for effect of cerebral infarction and hemorrhage in clinic with animal's and pharmacological experimental results.

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Acute Toxicity Study of Modified Je-Ho-Tang in ICR Mice

  • Lee, In-Sun;Lee, Jeong-Hwa;Han, Jae-ll;Song, Woon-Heung;Kim, Mi-Yeon;Jeon, Won-Kyung
    • Korean Journal of Clinical Laboratory Science
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    • v.44 no.2
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    • pp.59-65
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    • 2012
  • Previous studies have shown that modified Je-Ho-Tang (MJHT) has anti-platelet effects. Je-Ho-Tang (JHT), a Korean court beverage, is a traditional Korean herbal medicine that has been used for the treatment of a disease attended by great thirst, and for prevention of illness in hot summers. We made MJHT from JHT by excluding honey. The present study was performed to determine the acute oral toxicity of crude extract of MJHT in male and female ICR mice. We investigated the in vivo single dose acute toxicity of MJHT hot-water extraction. This test was orally administered once by gavage to 20 mice of each sex received doses of 0 (control group), 1250, 2500 and 5000 mg/kg body weight. Mortalities, clinical findings, autopsy findings and body weight changes were monitored daily for 14 days following the administration. We observed survival rates, general toxicities, changes of body weight, and autopsy. No significant lethality was observed after single oral administration of MJHT at the different dosages. Autopsies on the animals revealed no gross abnormalities. Therefore, the LD50 value of MJHT for ICR mice was estimated more than 5000 mg/kg by the oral route. These results suggest that no toxic dose level of MJHT in mice is considered to be more than 5000 mg/kg. Consequently, it was concluded that MJHT have no effect on acute toxicity and side effect in ICR mice.

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Inhibitory Effect of the Ethanolic Seed Extract of Trichosanthes kirilowii on Angiogenesis in Human Umbilical Vein Endothelial Cells (과루인 에탄올 추출물의 혈관신생 억제효과)

  • Shin-Hyung, Park;Hyun-Ji, Park
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.36 no.5
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    • pp.175-180
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    • 2022
  • The seeds of Trichosanthes kirilowii (STK) used in traditional Oriental medicine for the treatment of dry cough and constipation have diverse pharmacological activities, including hypolipidemic, antioxidant, immunosuppressive, and anticancer effects. However, the effect of STK on angiogenesis has not been studied yet. In this study, we investigated whether the ethanolic extract of STK (ESTK) can regulate the migration and tube formation of human umbilical vein endothelial cells (HUVECs) and explored the underlying mechanism. Results of transwell assay showed that ESTK treatment dose-dependently suppressed the migration of HUVECs. The conditioned medium collected from H1299 human lung cancer cells was used as a chemoattractant. Our observation suggests that ESTK would inhibit the recruitment of endothelial cells into tumors. In addition, ESTK treatment significantly reduced the tube formation of HUVECs. As a molecular mechanism, we found that vascular endothelial growth factor (VEGF)-induced phosphorylation of VEGF receptor 2 (VEGFR2) was completely blocked by ESTK treatment. The expression of angiogenic factors, including VEGFA, fibroblast growth factor 2 (FGF2), angiopoietin, placental growth factor (PGF), platelet derived growth factor (PDGF), angiogenin, and tumor necrosis factor (TNF)-α, was commonly decreased by ESTK treatment in H1299 cells, indicating that ESTK would reduce the production of angiogenic factors from cancer cells. Taken together, our results clearly demonstrated that ESTK exhibited anti-angiogenic effects in HUVECs, which provides another possible mechanism underlying the anticancer activities of STK.