Anti-platelet Aggregation Effects Research Articles

Evaluation of Anti-Platelet Aggregation Effect of Some Allium Species.

Epidemiologic studies show that the cardiovascular diseases are associated with multiple factors such as raised serum total cholesterol, increased LDL, increased platelet aggregation, hypertension and smoking. In-vitro studies have confirmed the ability of some plants of Allium species to reduce these parameters. Therefore, we evaluated anti-platelet aggregation effect of some Allium species (Allium ampeloprasum, A. hirtifolium, A. haemanthoides, A. vavillovi, A. atroviolaceum, A. jesdianum, A. shelkovnikovii) using arachidonic acid (AA) and adenosine diphosphate (ADP) as platelet aggregation inducers. The screening results for methanolic extract of Allium species showed that the maximum effect of anti-platelet aggregation was related to A. atroviolaceum. This extract inhibited the in-vitro platelet aggregation induced by AA and ADP with IC50 values of 0.4881 (0.4826-0.4937) mg/ml and 0.4945 (0.4137-0.5911) mg/ml respectively. These results support the hypothesis that the dietary intake of Allium could be beneficial for prevention of cardiovascular diseases.

Comparative Study for Pharmacological Action of Corydalis Rhizoma before and after Processing

ObjectiveTo clarify the rationality and to provide reasonable usage references of processed Corydalis Rhizoma (CR) in clinic by comparing respectively pharmacological actions including analgesic, anti-inflammation, antiplatelet aggregation and spasmolysis of Yuanhu Zhitong Tablet (YZT) and Yanhusuo Decoction (YD) constituted with raw CR (RCR) or processed CR (PCR). MethodsThe hot-board, acetic-acid-induced twisting experiments and mouse auricular swelling model by injecting xylene in the abdomen of mouse were adopted to investigate the analgesic and anti-inflammatory effects of the four formulas on Kunming mice; The experiment of contractile activity on isolated rat intestine smooth muscle on Wistar rats was applied to observing the spasmolysis effect of the four formulas; The experiments of platelet aggregation induced by ADP or collagen on Wistar rats by turbidimetry method were used to observe the anti-platelet aggregation effect of the four formulas. ResultsCompared with RCR in two prescriptions, PCR displayed better analgesic effect (P < 0.05, 0.01), while there was no difference on anti-inflammatory effect; Inhibition of the two prescriptions on smooth muscle spasm was presented well, and the prescription YD with PCR was remarkable (P < 0.05, 0.01); Compared with the blank group, the two prescriptions showed outstanding effects on anti-platelet aggregation (P < 0.01), but no difference between RCR and PCR in two prescriptions. ConclusionPCR can improve the analgesic effect of prescription YZT and intensify the spasmolysis effect of prescription YD, which can be explained by the Chinese medicine processing regulation. Therefore, PCR is suggested to be chosen in YZT and YD used to cure pain symptoms.

Potential therapeutic agents for circulatory diseases from Bauhinia glauca Benth.subsp. pernervosa. (Da Ye Guan Men).

Because of platelets as critical factor in the formation of pathogenic thrombi, anti-platelet activities have been selected as therapeutic target for various circulatory diseases. In order to find potential therapeutic agents, bioassay-directed separation of Bauhinia glauca Benth.subsp. pernervosa. (called Da Ye Guan Men as a traditional Chinese medicine) was performed to get 29 main components (compounds 1-29) from the bioactive part of this herbal. It was the first time to focus on the composition with anti-platelet aggregation activities for this traditional Chinese medicine. The constituents, characterized from the effective extract, were established on the basis of extensive spectral data analysis. Then their anti-platelet aggregation effects were evaluated systematically. On the basis of the chemical profile and biological assay, it was suggested that the flavonoid composition (5 and 18) should be responsible for the anti-platelet aggregation of the herbal because of their significant activities. The primary structure and activity relationship was also discussed briefly.

New organic nitrate-containing benzyloxy isonipecotanilide derivatives with vasodilatory and anti-platelet activity

A number of new nitric oxide (NO)-precursors were synthesized by grafting nitrate-containing moieties on the structures of the benzyloxy isonipecotanilide derivatives 1 and 2 already reported as moderately potent antiplatelet agents. Various nitrooxy (ONO2)-alkyl side chains were covalently linked to the piperidine nitrogen of the parent compounds through carbamate and amide linkage, and the synthesis of a benzyl nitrate analog (15) of compound 1 was also achieved. The in vitro vasodilatory activities, as well as platelet anti-aggregatory effects, of the newly synthesized organic nitrates were assessed. The (ONO2)methyl carbamate-based derivative 5a and the benzyl nitrate analog 15, which on the other hand retain activity as inhibitors of ADP-induced platelet aggregation, exhibited strong NO-mediated vasodilatory effects on pre-contracted rat aorta strips, with EC50 values in the low nanomolar range (13 and 29nM, respectively). Experiments carried out with the selectively inhibited soluble guanylate cyclase (sGC), which is the key enzyme of the NO-mediated pathway leading to vascular smooth muscle relaxation, confirmed the involvement of NO in the observed vasodilation. The nitrate derivatives proved to be stable in acidic aqueous solution and at pH 7.4. In human serum, unlike 5a, which showed not to undergo enzyme-catalyzed decomposition, the other tested (ONO2)-alkyl carbamate-based compounds (5b and 5e) and benzyl nitrate 15 underwent a faster degradation. However, their decomposition rates in serum were quite slow (t½>2.6h), which suggests that nitrate moiety is poorly metabolized in blood plasma and that much of the in vitro anti-platelet activity has to be attributed to the intact (ONO2)-containing molecules.

Pharmacokinetics, bioavailability, and metabolism of Notoginsenoside Fc in rats by liquid chromatography/electrospray ionization tandem mass spectrometry

Notoginsenoside Fc (NGFc) is a protopanaxadiol-type (PPD-type) saponin from Panax notoginseng, which has perfect anti-platelet aggregatory effect. However, its pharmacokinetics and metabolism in vivo remain unknown. In this study, a simple and sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC–MS/MS) method was first developed for the determination of NGFc in rat plasma. After methanol-mediated protein precipitation, separation was achieved on a C18 column with MS detection operated in negative SRM mode at m/z 604.56→m/z 783.90 and m/z 799.93→m/z 637.64 for NGFc and IS, respectively. The assay was linear over the concentration range (r>0.995) with the LLOQ of 0.002μg/ml. The intra- and inter-day precisions (R.S.D.) were 2.45–12.36% and 3.67–14.22%, respectively; whereas accuracy ranged from (R.R.) 93.90% to 99.41%. The extraction recovery, stability, and matrix effect were within the acceptable limits. The validated LC–MS/MS method was successfully applied to the pre-clinical pharmacokinetic studies of NGFc in rat. After oral and intravenous administration, NGFc showed dose-independent pharmacokinetic behaviors with a t1/2 of >22h and its oral bioavailability was 0.10–0.14%. In addition, a total of 10 metabolites were detected and structurally characterized by UPLC–Q/TOF-MS technique, which suggested that deglycosylation was the major metabolic pathway for NGFc in rats.

Prostaglandin E1 Treatment for Lumbar Spinal Canal Stenosis: Review of the Literature.

The important pathophysiologic factor of neurogenic intermittent claudication (NIC) in lumbar spinal canal stenosis (LSCS) has been reported to be the reduction in intraneural blood flow and a state of relative ischemia in nerve tissues. Prostaglandin E1 (PGE1) presumably improves symptoms in patients with LSCS by improving the blood flow in the cauda equina and nerve roots through its vasodilation and antiplatelet aggregation effects. The purpose of the study was to summarize the results of previous studies regarding PGE1 treatment for LSCS and to describe the details of PGE1 treatment to all physicians who take care of patients with LSCS. Review of the literature. There are 3 PGE1-related products that have been used clinically for the treatment of LSCS: PGE1, lipo-PGE1, and limaprost (PGE1 derivative). Experimental studies have been performed to verify the efficacy of PGE1 treatment for LSCS. Many studies have reported clinical outcomes of PGE1 treatment in patients with LSCS. Overall, previous studies examining PGE1 treatment for LSCS demonstrate improvement in several clinical outcome measures such as the visual analog scale, Japanese Orthopaedic Association score, and NIC distance, although most of the studies have only short-term follow-up. Based on the results of previous studies, PGE1 treatment may be an option as a conservative treatment for LSCS. However, future studies with high-quality and long-term follow-up are necessary. Future studies also should include refinement of indications, administration period, as well as comparisons between PGE1 treatment and other conservative treatments such as epidural injection.

Antiplatelet Aggregation and Antithrombosis Efficiency of Peptides in the Snake Venom ofDeinagkistrodon acutus: Isolation, Identification, and Evaluation

Two peptides of Pt-A (Glu-Asn-Trp 429 Da) and Pt-B (Glu-Gln-Trp 443 Da) were isolated from venom liquor of Deinagkistrodon acutus. Their antiplatelet aggregation effects were evaluated with platelet-rich human plasma in vitro; the respective IC50 of Pt-A and Pt-B was 66 μM and 203 μM. Both peptides exhibited protection effects on ADP-induced paralysis in mice. After ADP administration, the paralysis time of different concentration of Pt-A and Pt-B lasted as the following: 80 mg/kg Pt-B (152.8 ± 57.8 s) < 40 mg/kg Pt-A (163.5 ± 59.8 s) < 20 mg/kg Pt-A (253.5 ± 74.5 s) < 4 mg/kg clopidogrel (a positive control, 254.5 ± 41.97 s) < 40 mg/kg Pt-B (400.8 ± 35.9 s) < 10 mg/kg Pt-A (422.8 ± 55.4 s), all of which were statistically shorter than the saline treatment (666 ± 28 s). Pulmonary tissue biopsy confirmed that Pt-A and Pt-B prevented the formation of thrombi in the lung. Unlike ADP injection alone, which caused significant reduction of peripheral platelet count, Pt-A treatment prevented the drop of peripheral platelet counts; interestingly, Pt-B could not, even though the same amount of Pt-B also showed protection effects on ADP-induced paralysis and thrombosis. More importantly, intravenous injection of Pt-A and Pt-B did not significantly increase the hemorrhage risks as clopidogrel.

Molecular mechanism of tanshinone IIA and cryptotanshinone in platelet anti-aggregating effects: an integrated study of pharmacology and computational analysis

Tanshinone IIA and cryptotanshinone are two pharmacologically active diterpenoids extracted from the roots of Salvia milthiorriza Bunge, a plant used in Chinese traditional medicine for the treatment of some cardiovascular and cerebrovascular disease. Until now, the molecular mechanisms of action of these two diterpenoids on platelets are partially known. To clarify this aspect, here we utilized an integrated study of pharmacology and computational analysis.Our results demonstrate that cryptotanshinone is able to inhibit in a concentration dependent manner the rat platelet aggregation and also is endowed of Gi-coupled P2Y12 receptor antagonist as demonstrated by docking studies. This computational method was also performed for tanshinone IIA demonstrating even for this diterpenoid an interaction with the same receptor.The findings from our study enable a better understanding of tanshinone IIA and cryptotanshinone biological properties, which could ultimately lead to the development of novel pharmaceutical strategies for the treatment and/or prevention of some cardiovascular disease.

Effects of danshensu on platelet aggregation and thrombosis: in vivo arteriovenous shunt and venous thrombosis models in rats.

Danshensu, a type of dihydroxyphenyl lactic acid, is one of the most abundant active phenolic acids in the dried root of Salvia miltiorrhizae (Lamiaceae)—widely used traditional Chinese medicine. The effects of danshensu on platelet aggregation and thrombus formation in rats were examined using various methods. It was found that danshensu significantly reduced thrombus weight in 2 experimental thrombosis models; dose-dependent inhibition of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation occurred in normal and blood stasis-induced rats; Danshensu also significantly mitigated blood viscosity, plasma viscosity and hematocrit levels. Moreover, danshensu significantly inhibited venous thrombosis-induced expression of cyclooxygenases-2 (COX-2) rather than cyclooxygenases-1(COX-1) in the venous walls, down regulated thromboxane B2 (TXB2) and up regulated 6-keto prostaglandin F1α (6-keto-PGF1α), normalizing the TXB2/6-keto-PGF1α ratio. In addition, danshensu did not induce gastric lesions and even had protective effects on aspirin-induced ulcer formation at doses as high as 60 mg/kg. These findings suggest that the antithrombotic and antiplatelet aggregation effects of danshensu are attributed to its highly selective inhibition of COX-2 and ability to normalize the thromboxane A2(TXA2)/prostacyclin(PGI2) balance. These findings suggest that danshensu have great prospects in antithrombotic and antiplatelet therapy.

The constituents of roots and stems of Illigera luzonensis and their anti-platelet aggregation effects.

Phytochemical investigation of the roots and stems of Illigera luzonensis afforded two new aporphine alkaloids (1) and (2), one new bisdehydroaporphine alkaloid (3), and one new benzenoid (4), along with 28 known structures. The structures of new compounds were elucidated by spectral and MS analysis. Among the isolated compounds, (1) and (4–13) were subjected into the examination for their inhibitory effects on the aggregation of washed rabbit platelets.

English

Ischemia-reperfusion (IR) syndrome is defined as injury caused by the restoration of coronary flow after a period of ischemia. The pathophysiology of ischemia-reperfusion injury involves cellular effect of ischemia, reactive oxygen species and inflammatory cascade. Flavonoids and polyphenols possess unique antioxidant properties and other protective activities which are beneficial for ischemia-reperfusion injury. It is found that flavonoids and polyphenols prevent production of reactive oxygen species and thereby inhibit oxidation of cellular components and also block propagation of oxidative reactions. They also increase the activity of endogenous antioxidant enzymes such as superoxide dismutase and catalase during ischemia-reperfusion injury. Flavonoids also possess anti-inflammatory, anti-platelet aggregation and vasodilatory effects through different mechanism. This review scrutinize to what extent flavonoids and polyphenols play a role in moderating ischemia-reperfusion mediated injury with special emphasis on pathophysiology of heart ischemic-reperfusion injury. &nbsp; Key words: Ischemia, reperfusion, heart, flavonoids, polyphenols, antioxidant.&nbsp

Synthesis of analogues of gingerol and shogaol, the active pungent principles from the rhizomes of Zingiber officinale and evaluation of their anti-platelet aggregation effects.

The present study was aimed at discovering novel biologically active compounds based on the skeletons of gingerol and shogaol, the pungent principles from the rhizomes of Zingiber officinale. Therefore, eight groups of analogues were synthesized and examined for their inhibitory activities of platelet aggregation induced by arachidonic acid, collagen, platelet activating factor, and thrombin. Among the tested compounds, [6]-paradol (5b) exhibited the most significant anti-platelet aggregation activity. It was the most potent candidate, which could be used in further investigation to explore new drug leads.

MC-002 exhibits positive effects against platelets aggregation and endothelial dysfunction through thromboxane A 2 inhibition

Thromboxane A2 (TXA2) induces platelet aggregation and vasoconstriction, and agents that inhibit TXA2 production or interaction with receptors may exert potential application in stroke therapy. To illustrate the platelet aggregation antagonistic and endothelial protective effect of (E) - 3 - (3 - methoxy - 4 - ((3, 5, 6 - trimethylpyrazin - 2 - yl) methoxy) phenyl) sodium acrylate (MC-002) through TXA2 inhibition and underline mechanisms. Platelets aggregation and thoracic aorta ring contraction of rabbits were induced by U46619. Human umbilical vein endothelial cells (HUVECs) were further applied to explore the protective effect of MC-002 on endothelium when exposed to tumor necrosis factor - α (TNF-α). MTT method was used to assess cell damage, and ELISA analysis was exerted to estimate nitrogen monoxide (NO), endothelin-1 (ET-1), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) releasing. Fluorescence spectrophotometry was conducted to determine intracellular calcium concentration ([Ca(2+)]i), and western blotting method was applied to evaluate the protein expressions of intracellular adhesion molecule-1 (ICAM-1), P-selectin and nuclear factor-kappa B (NF-κB). TXA2 analog U46619 mediated obvious platelet aggregation and vasoconstriction. MC-002 inhibited platelet aggregation through administration in vivo and incubation with platelet in vitro, and relaxed aorta ring in endothelium dependent manner. MC-002 alleviated cell damage, [Ca(2+)]i overload, ET-1 overexcretion and TXB2 activation, but improved NO availability reduction in HUVECs treated with TNF-α. Furthermore, MC-002 downregulated ICAM-1, P-selectin and NF-κB overexpression induced by TNF-α. In conclusion, MC-002 exerted antiplatelet aggregation effect through TXA2 inhibition and relieved inflammatory injury of endothelial cells through NF-κB signal pathway.

A Comparative Study on Chemical Composition and Pharmacological Effects of &amp;lt;i&amp;gt;Paecilomyces hepiali&amp;lt;/i&amp;gt; and Wild &amp;lt;i&amp;gt;Ophiocordyceps sinensis&amp;lt;/i&amp;gt;

This study looked at comparison of chemical components and pharmacological activity between wild Ophiocordyceps sinensis and Paecilomyces hepiali. The chemical components investigated included amino acids, vitamins, dietary elements, protein, lipid, ash, carbohydrates, crude fibre, ergosterol and mannitol. Studies on pharmacological activity included anti-platelet aggregation, inhibitory effect on IL-8 gene expression, anti-mutagenic activity, skin whitening effect and impro- vement activity on human skin texture. The results show that P. hepiali has a larger total content of seven essential amino acids (leucine, lysine, methionine, phenylalanine, tryptophan, tyrosine and valine) than O. sinensis, 8580 mg/100g and 6180 mg/100g respectively. The total content of dietary elements analysed (potassium, magnesium, zinc, copper, manganese and selenium) was also higher in P. hepiali (3135 mg/100g) than that in O. sinensis (2445 mg/100g). The total content of four vitamins (B1, B2, B6 and E) was almost equal for both fungi. Paecilomyces hepiali had more content of protein, lipid, ash, carbohydrate, ergosterol and mannitol than O. sinensis. However, the contents of lipid and ash were not significantly different between the two fungi. The hot water extract of P. hepiali has been shown to have a number of pharmacological effects which include 1) inhibition of aggregation on human platelet, 2) inhibition of IL-8 gene expression, 3) anti-mutage- nic activity, 4) inhibition effect on production of melanin, and 5) improvement on human skin texture. Anti-platelet aggregation effects on human platelet, inhibition of IL-8 gene expression, anti-mutagenic activity and improvement effect on human skin texture were greater in P. hepiali treatments than that in wild O. sinensis.

The preliminary study on the antithrombotic mechanism of glycosaminoglycan from mactra veneriformis

The effect of glycosaminoglycan from Mactra veneriformis on deep venous thrombosis of rats was observed, and the preliminary antithrombotic mechanism of glycosaminoglycan was explained. The results showed that when the glycosaminoglycan was injected intravenously into rats within the dose range of 0.0313-1 mg/kg, the antithrombotic effect increased as the dose increased. When the dose was increased to and exceeded 0.125 mg/kg, deep venous thrombosis caused by blood stagnation was inhibited significantly or extremely remarkably (P < 0.05, P < 0.01), while the intensity was similar to that of the tool drug heparin sodium at the same dose and weaker than that of heparin calcium of low molecular weight at three times' dose in clinics. Three doses (0.1, 0.4 and 1.6 mg/kg) of glycosaminoglycan were intravenously injected via mice tail, resulting in an extremely significant increase of activated partial thromboplastin time (APTT) and thrombin time (TT) (P < 0.01), no significant change of prothrombin time (PT) (P > 0.05), and a weaker anticoagulant effect than that of heparin sodium. In-vitro experiments demonstrated that except for the 2 μg/ml of glycosaminoglycan (P > 0.05), other final concentration groups significantly or extremely significantly prolonged the APPT, TT and PT of rabbits (P < 0.05, P < 0.01), but with a slightly weaker anticoagulant effect than that of heparin sodium; The antiplatelet aggregation experiments using big-eared rabbits manifested that glycosaminoglycan markedly decreased the maximum aggregation percentage of rabbits blood platelet (P < 0.01), which indicated that it had good antiplatelet aggregation effect, but the intensity was weaker than the positive control drug, Ozagrel sodium.

Early anti-platelet aggregation effect and mechanism of endothelial nitric oxide synthase gene-modified CD34 + cells

Objective Objective To evaluate the anti-platelet aggregation effect of nitric oxide synthase gene modified-CD34 + bone marrow stem cells in vitro,and to explore its mechanism.Methods Extracted bone marrow from canine,isolated CD34 + cells by immunomagnetic,transfected endothelial nitric oxide synthase (eNOS) gene to CD34 + cells with liposomes,endothelial cell growth factor induced and amplified.Detected the expression of tissue factor (TF) stimulated by lipopolysaccharide (LPS),and performed platelet adhesion assay to detect the anti-platelet aggregation effect of eNOS-CD34 + cells in vitro.Results Platelet adhesion assay in vitro showed that the inhibition of platelet aggregation in eNOS-CD34 + cells was significantly higher than that in non-transfected group.After LPS stimulation,TF immunofluorescence of eNOS-CD34 + cells was significantly weaker than non-transfected group.Western blot detected that the expression of TF protein in eNOS-CD34 + cells was significantly weaker than that in non-transfected group.Conclusion eNOS gene transfection significantly increases anti-platelet aggregation effect of CD34 + bone marrow stem cells in vitro,its mechanism may be related to the inhibition of TF expression. Key words: Nitric oxide synthase ; Endothelialization ; Antithrombotic ; Tissue factor

Anti-platelet Aggregation and Anti-thrombotic Effects of Marine Natural Products Sargahydroquinoic Acid and Sargaquinoic Acid

E-mail: sjlee@kwandong.ac.krReceived June 18, 2013, Accepted July 16, 2013Key Words : Marine natural products, Anti-platelet aggregation, Anti-thrombotic effects, Sargahydroquinoicacid, Sargaquinoic acidPlatelets circulate in blood and their activity is regulatedby nitric oxide (NO) and prostaglandin I

Iridoid glycosides extracted from Zhizi (Fructus Gardeniae) decrease collagen-induced platelet aggregation and reduce carotid artery thrombosis in an in vivo rat model

ObjectiveTo investigate the anti-platelet aggregation and antithrombotic effects in rats of iridoid glycosides extracted from Zhizi (Fructus Gardeniae). MethodsThe present study evaluated the antithrombotic activity of iridoid glycosides (IGs) in a rat model of carotid artery thrombosis. The effects on coagulation, such as thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT), and the effect on collagen-induced platelet aggregation in vivo were investigated. Rats were intragastrically administered IGs (50, 100 or 200 mg/kg) twice daily for 3 days. ResultsIGs were shown for the first time to have an antithrombotic action through the inhibition of platelet aggregation, with little effect on the coagulation time of peripheral blood. Our results also showed that IGs may significantly and dose-dependently reduce arterial thrombus load in a model of carotid artery thrombosis and inhibit collagen-induced platelet aggregation in rats. IGs (100 or 200 mg/kg) had no significant effect on APTT and PT, but did lengthen TT at a higher dose. ConclusionThese data, together with the previously reported neuroprotective effects of IGs in rats with cerebral ischemia, suggest that the antithrombotic action of IGs may potentially contribute to the treatment of cerebral ischemic diseases, including cerebral apoplexy.

Abstract 514: Cilostazol Attenuated Angiotensin II-induced Abdominal Aortic Aneurysms Thorough Anti-inflammatory Effect in Apolipoprotein E-deficient Mice

Objective Chronic angiotensin II (AngII) infusion promotes development of abdominal aortic aneurysms (AAAs) in mice. Previous studies have shown that local inflammation plays an important role on formation of AAAs. Cilostazol, a phosphodiesterase-3 inhibitor with antiplatelet aggregation and vasodilatory effects, exerts vasoprotective effect by inhibiting inflammation and superoxide generation in several experimental studies. The purpose of this study was to evaluate whether cilostazol influenced AngII-induced AAAs. Methods and Results Male apolipoprotein E deficient mice (8-12 weeks old) were fed with either normal diet or cilostazol-containing (0.1% wt/v) diet. After 1 week of cilostazol administration, mice were infused subcutaneously with either AngII (1,000 ng/kg/min, n = 16 -19) or saline (n = 5 - 6) by osmotic minipumps for 4 weeks. AngII equivalently increased systolic blood pressure, irrespective of cilostazol administration. Cilostazol had no effect on serum cholesterol concentrations, triglycerides, high-density lipoprotein-cholesterol, body weights, heart rates, and systolic blood pressures. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas that were attenuated by cilostazol administration (1.94 ± 0.16 mm vs 1.53 ± 0.17 mm, P &lt; 0.05). Cilostazol diminished AngII-induced increase of aortic MMP-2 activity and ICAM-1 protein expression as determined by gelatin zymography and Western blot, respectively (P &lt; 0.05, each). Aortic mRNA expression of inflammatory cytokines such as MCP-1, IL-1β, osteopontin, and COX-2 was reduced by cilostazol administration (P &lt; 0.05). In vitro, TNF-α increased MCP-1, ICAM-1 and VCAM-1 mRNA expression in mouse aortic endothelial cells. These enhancements were decreased by incubation with cilostazol (P &lt; 0.05). Conclusion Cilostazol attenuated AngII-induced AAAs thorough its anti-inflammatory effect in male apolipoprotein E deficient mice.

Effects of Shiitake Mushroom on Anti-platelet Aggregation and Anti-thrombotic

In in vitro study, the anti-platelet aggregation effect of Shiitake mushroom extract was examined by measuring the collagen induced platelet aggregation and the DPPH radical scavenging. In in vitro study, anti-thrombotic effect of Shiitake mushroom extract was examined using the carotid artery thrombosis rat model. Carotid artery thrombosis rat model was made by 35% FeCl₃ treatment. After that, we investigate thrombus weight and blood flow. In platelet aggregation test, the extract significantly inhibited platelet aggregation in a concentration dependent manner(p<.001). Also, extract increased DPPH radical scavenging activity in a concentration dependent manner. Extract significantly inhibited thrombus weight to compare with control group. And blood passage time were shorter in the Shiitake mushroom extract supplemented groups than in control group. These results provide experimental evidence that Shiitake mushroom can be used to prevent platelet aggregation and thrombosis, then could apply the clinical diseases such as cardiovascular disease, and so on.