Anti-platelet Aggregation Effects Research Articles

Effects of Acetylsalicylic Acid in Preterm Preeclampsia Prevention

Acetylsalicylic acid, classified under the non-steroidal anti-inflammatory drugs (NSAIDS) has well known anti-inflammatory, anti-pyretic properties, anti-platelet aggregation effect and analgesic properties. Pre-eclampsia (PE) is a pathology of pregnancy characterized by the onset of hypertension and often accompanied by the lost of significant amount of protein in the urine. In pregnant women with risk of preeclampsia, low doses of aspirin have been shown to have a beneficial effect on the incidence of this disorder. Using a retrospective design, we screened for preeclampsia all pregnancies followed in a time interval of 2 years. We have observed that in preeclampsia high risk patients based on the screening done between 11 to 13 weeks and 6 days, the administration of low doses of acetylsalicylic acid reduced the burden of disease. Identifying the pregnancy having high risk for preeclampsia in the first trimester helps us in decision making for initiating prophylactic treatment with Aspirin.

The Multivariate Regression Statistics Strategy to Investigate Content-Effect Correlation of Multiple Components in Traditional Chinese Medicine Based on a Partial Least Squares Method

Amultivariate regression statisticstrategy was developed to clarify multi-components content-effect correlation ofpanaxginseng saponins extract and predict the pharmacological effect by components content. In example 1, firstly, we compared pharmacological effects between panax ginseng saponins extract and individual saponin combinations. Secondly, we examined the anti-platelet aggregation effect in seven different saponin combinations of ginsenoside Rb1, Rg1, Rh, Rd, Ra3 and notoginsenoside R1. Finally, the correlation between anti-platelet aggregation and the content of multiple components was analyzed by a partial least squares algorithm. In example 2, firstly, 18 common peaks were identified in ten different batches of panax ginseng saponins extracts from different origins. Then, we investigated the anti-myocardial ischemia reperfusion injury effects of the ten different panax ginseng saponins extracts. Finally, the correlation between the fingerprints and the cardioprotective effects was analyzed by a partial least squares algorithm. Both in example 1 and 2, the relationship between the components content and pharmacological effect was modeled well by the partial least squares regression equations. Importantly, the predicted effect curve was close to the observed data of dot marked on the partial least squares regression model. This study has given evidences that themulti-component content is a promising information for predicting the pharmacological effects of traditional Chinese medicine.

Cilostazol Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysms but Not Atherosclerosis in Apolipoprotein E-Deficient Mice.

Abdominal aortic aneurysm (AAA) is a permanent dilation of the abdominal aorta associated with rupture, which frequently results in fatal consequences. AAA tissue is commonly characterized by localized structural deterioration accompanied with inflammation and profound accumulation of leukocytes, although the specific function of these cells is unknown. Cilostazol, a phosphodiesterase III inhibitor, is commonly used for patients with peripheral vascular disease or stroke because of its anti-platelet aggregation effect and anti-inflammatory effect, which is vasoprotective effect. In this study, we evaluated the effects of cilostazol on angiotensin II-induced AAA formation. Male apolipoprotein E-deficient mice were fed either normal diet or a diet containing cilostazol (0.1% wt/wt). After 1 week of diet consumption, mice were infused with angiotensin II (1000 ng/kg per minute) for 4 weeks. Angiotensin II infusion increased maximal diameters of abdominal aortas, whereas cilostazol administration significantly attenuated dilatation of abdominal aortas, thereby, reducing AAA incidence. Cilostazol also reduced macrophage accumulation, matrix metalloproteinases activation, and inflammatory gene expression in the aortic media. In cultured vascular endothelial cells, cilostazol reduced expression of inflammatory cytokines and adhesive molecules through activation of the cAMP-PKA (protein kinase A) pathway. Cilostazol attenuated angiotensin II-induced AAA formation by its anti-inflammatory effect through phosphodiesterase III inhibition in the aortic wall. Cilostazol may be a promising new therapeutic option for AAAs.

A systematic review on the cardiovascular pharmacology of Emblica officinalis Gaertn.

Introduction: The Emblica officinalis (EO) fruit has traditionally been considered as a cardioactive medication and has demonstrated remarkable cardiovascular effects in the pharmacological literature. The present study systematically reviews EO’s potential for prevention and therapy of cardiovascular diseases (CVD). Methods: PubMed, ScienceDirect, Scopus, Proquest, Ebsco, Google, Google Scholar, Ovid, and Cochrane databases were searched from 1966 to 2017 for the English and non-English literature using the terms including the cognates of EO including amla, Emblic myrobalan, Emblica officinalis, Emblica pectinata , Indian gooseberry, and Phyllanthus emblica together with antioxidant, arrhythmia, cardioprotective, cardiotoxicity, heart disease, heart failure, hyperlipidemia, hypertension, myocardial dysfunction, and oxidative stress. The inclusion criteria were in vitro, animal, and clinical cardiovascular pharmacological studies conducted on EO and full-text accessibility. The exclusion criterion was studies in which a combination of EO and at least one other plant was investigated. The reference lists of the retrieved articles were also searched manually for additional eligible articles. The methodological quality of clinical trials was assessed by the Jadad scale, and animal studies were evaluated by the ARRIVE checklist. Results: Nineteen articles concerning the cardiovascular pharmacological effects of EO were included in this review. The plant has shown antiatherogenic, anticoagulant, hypolipidemic, antihypertensive, antioxidant, antiplatelet, and vasodilatory effects as well as lipid deposition inhibitory properties. Moreover, it prevents from doxorubicin and isoproterenol cardiotoxicity and myocardial ischemia/reperfusion injury, and improves vascular endothelial function in animal studies. Some high-quality clinical studies report the vasodilatory and myocardial antioxidant properties as well as anti-platelet aggregation effects of this plant. Conclusion: EO influences various cardiovascular risk-factors. However, there is not sufficient evidence to confirm the plant efficacy in preventing and treating CVD.

Inhibited effects of CAPE-pNO2 on cervical carcinoma in vivo and in vitro and its detected metabolites.

The development of advanced cervical cancer therapies is a particularly urgent need due to the strong side effects and toxicities of current treatments. Caffeic acid phenethyl ester (CAPE) exhibits broad-spectrum antitumor activities and little toxicity or side effects. In our previous study, caffeic acid para-nitro phenethyl ester (CAPE-pNO2) significantly improved the effect of anti-platelet aggregation and attenuated myocardial ischemia. Based on this finding, we aimed to further explore the antitumor activity of CAPE-pNO2 in cervical cancer cells and tumor xenografts. In addition, we assessed the biotransformation of CAPE-pNO2 in cervical cancer cells. Our study demonstrated that both CAPE and CAPE-pNO2 can inhibit cell proliferation via the induction of G2/M cell cycle arrest. More importantly, CAPE-pNO2 dramatically induced cell apoptosis via significant down-regulation of pro-caspase-3, pro-caspase-9, Bcl-2, Cyclin B1 and Cdc2 and up-regulation of cleaved-caspase-3, Bax, CytoC and P21Cip1. Moreover, CAPE and CAPE-pNO2 significantly suppressed the growth and angiogenesis of nude mice xenografts. CAPE and CAPE-pNO2 were found to degrade into four and six metabolites, respectively. The metabolites of CAPE and CAPE-pNO2 were different, and the major metabolic pathway may be phase II reactions. These results suggest that CAPE-pNO2 induced cell apoptosis and cell cycle arrest via a strong regulatory effect on relevant apoptotic proteins. Therefore, CAPE-pNO2 should be further studied as a potent anti-cancer agent.

Antiplatelet activity, molecular docking and QSAR study of novel N′-arylmethylidene-3-methyl-1-phenyl-6-p-chlorophenyl-1H-pyrazolo[3,4-b] pyridine-4-carbohydrazides

A series of novel N′-arylmethylidene-3-methyl-1-phenyl-6-p-chlorophenyl-1H-pyrazolo[3,4-b]pyridine-4-carbohydrazide (2a–2t) has been synthesized from hydrazide (1). The structures of newly synthesized compounds were confirmed by FT-IR, EI-MS, 1H NMR and 13C NMR techniques. The title compounds were evaluated for antioxidant and antiplatelet aggregation effect induced by arachidonic acid (AA) and collagen. All the compounds have exhibited high antioxidant potential and antiplatelet activity but (2c, 2e, 2f, 2g, 2i, 2m, 2o and 2q) have revealed superlative antiplatelet activity. The molecular docking against cyclooxygenase-1 and 2 (COX-1 and COX-2) and quantitative structure-activity relationship (QSAR) were performed in describing their antiplatelet potential against AA and collagen along with antioxidant potential determined by ABTS, DPPH and iron chelating methods. The molecular docking study exhibited that compounds (2c, 2e, 2f, 2g, 2i, 2l, 2m, 2o and 2q) were found to be active against COX-1 while 2o compound also showed activity against COX-2. Compounds 2g and 2l were found to have higher energy stabilization values in comparison to Aspirin. Computational evaluations both molecular docking and QSAR are in good agreement with antiplatelet and antioxidant activities of the compounds (2a–2t). All the compounds especially 2g, 2l, 2m might be promising antiplatelet agents and might be helpful in the synthesis of new drugs for the treatment of cardiovascular and anti-inflammatory diseases.

Anti-platelet aggregation effects of extracts from Arbutus unedo leaves

It is well known that platelet hyperactivity is a risk factor for cardiovascular diseases such as atherosclerosis, stroke and myocardial infarction. This study aimed to examine the effects of extracts enriched in flavonoids obtained from Arbutus unedo leaves on platelet aggregation. Rat platelets were prepared and incubated in vitro with different doses of the tested extracts, and aggregation was trigged by physiological agonists. Platelet treatment with increasing concentrations (0.1 - 1 mg/ml) of diethyl ether extract (genins = free flavonoids) or ethyl acetate extract (hetrosidic flavonoids) inhibited platelet aggregation evoked by thrombin in a concentration-dependant manner. The IC50 values were 0.22 ± 0.03 and 0.36 ± 0.05 mg/ml for genins and heterosidic flavonoids respectively. Treatment with Arbutus unedo extracts also significantly reduced the initial rate of platelet aggregation. At 1 mg/ml, the rate inhibition was 97.8 ± 0.74 and 90.8 ± 1.55 % for genins and heterosidic flavonoids respectively. In addition, flavonoids significantly inhibited platelet aggregation induced by ADP, collagen or epinephrine. We conclude that Arbutus unedo extracts show antiaggregant effects due mainly to flavonoids. These results may partly explain the traditional use of Arbutus unedo leaves for the treatment of cardiovascular disorders such as hypertension.

Antiplatelet aggregation bioactivity of Polygoni Multiflori Radix with chemical fingerprints and spectrum-effect correlation analysis

To explore the active substance of antiplatelet aggregation of Polygoni Multiflori Radix by using chemical fingerprints and antiplatelet aggregation bioactivity test for spectrum-effect correlation analysis. The Polygoni Multiflori Radix was tested by antiplatelet aggregation in vitro, and the results showed that 50% aqueous ethanol extract of Polygoni Multiflori Radix had more potent antiplatelet aggregation effect than 10% or 90% aqueous ethanol extract, and ultrasonic extraction was superior to refluxing extraction in the aspect of antiplatelet aggregation. The antiplatelet aggregation bioactivity of the different Polygoni Multiflori Radix extracts was evaluated and the results showed that the inhibition rate was 32.03%-74.56%. Spectrum-effect correlation analysis indicated that trans-stilbene glucoside, cis-stilbene glucoside and catechinic acid had higher correlation coefficient and they were 0.963 (P<0.01), 0.902 (P<0.01) and 0.656 (P<0.05) respectively; furthermore, all of the above three compounds demonstrated significant antiplatelet aggregation bioactivities. Considering their content difference in Polygoni Multiflori Radix, we calculated the relative active contributions, and the results suggested that trans-stilbene glucoside was the main active substance of Polygoni Multiflori Radix in the aspect of antiplatelet aggregation in vitro.

Effect on platelet aggregation activity: extracts from 31 Traditional Chinese Medicines with the property of activating blood and resolving stasis

OBJECTIVETo evaluate the anti-platelet aggregation effects of extracts from 31 Traditional Chinese Medicines (TCM) with the property of activating blood and resolving stasis in terms of TCM theory. METHODSThe 31 TCMs extracts were prepared using water, 90% ethanol and ethyl acetate., and the effects on anti-platelet aggregation were tested on a platelet aggregation analyzer in vitro with adenosine 5'-diphosphate, bovine thrombin and arachidonic acid (AA) as aggregation inducers, respectively. Aspirin was the positive control. RESULTSLots of the tested TCMs had inhibitory effects with concentration-dependent manner on platelet aggregations induced by various agonists. Especially, some of the TCMs such as Chuanxiong (Rhizoma Chuanxiong), Yanhusuo (Rhizoma Corydalis Yanhusuo) and Danshen (Radix Salviae Miltiorrhizae) showed good anti-platelet aggregation effect similar or higher than that in positive control group. CONCLUSIONThe study provided scientific references that several TCMs such as Chuanxiong (Rhizoma Chuanxiong), Yanhusuo (Rhizoma Corydalis Yanhusuo) and Danshen (Radix Salviae Miltiorrhizae), possess the property of anti-platelet aggregation.

Comparison of the effect of ticagrelor and clopidogrel on platelet functions and inflammation factor in patients with acute coronary syndrome after PCI

Objective To compare the effect of ticagrelor and clopidogrel on platelet functions and inflammation factor in patients with acute coronary syndrome(ACS) after PCI. Methods 180 patients with ACS who taken PCI were chosen and randomly divided into the observation group and the control group(90 cases in each group). All patients of the two groups were given conventional treatment, and the control group received clopidogrel treatment on the basis of routine therapy preoperation and postoperation, while the observation group received clopidogrel treatment on the basis of the control group treatment.Before treatment and 24 h, 7 d, 28 d after treatment, the C-reactive protein(CRP), interleukin 6(IL-6), tumor necrosis factor alpha(TNF-α), myeloperoxidase(MPO), soluble CD40 receptor(sCD40L), platelet maximum aggregation rate(MPAR) and P2Y12 response unit(PRU) in the two groups were recorded and compared, as well as the main cerebrovascular events after six months follow-up. Results In the two groups before treatment, MPAR and PRU had no statistically significant differences(t=0.41, 0.19, all P>0.05).24h, 7d and 28d after operation, MPAR and PRU were significantly decreased compared with before treatment(t≥2.09, all P 0.05).24h after treatment, CRP, sCD40L, IL-6 and TNF-α in the two groups all significantly increased(all P<0.05), and then decreased.24h, 7d, 28d after treatment, DCRP, sCD40L, IL-6 and TNF-α in the observation group were all significantly lower than those in the control group (t=60.79, 50.30, 27.95, 12.98, 40.29, 16.73, 15.03, 7.30, all P<0.05). And, the incidence rate of cardiovascular adverse events of the observation group was 2.22%, which was significantly lower than 10.00% of the control group(χ2=5.714, P<0.05). Conclusion Compared with clopidogrel, using ticagrelor to treat ACS patients after PCI has better antiplatelet aggregation and inflammation effects, which can reduce the incidence of cardiovascular adverse events. Key words: Coronary artery disease; Ticagrelor; Blood platelets; Chemokines

The Inhibitory Effect of Telmisartan on the Metabolism of Arachidonic Acid by CYP2C9 and CYP2C8: An in Vitro Study.

Epoxyeicosatorienoic acids (EETs) are generated from arachidonic acid (AA) by CYPs. EETs comprise four regioisomers (14,15-, 11,12-, 8,9-, and 5,6-EET). EETs show potent physiological effects, including vasodilation, anti-inflammation, myocardial preconditioning, and anti-platelet aggregation effects. We recently demonstrated that telmisartan, one of angiotensin II receptor blockers, inhibits AA metabolism by CYP enzymes, including CYP2C8, CYP2C9, and CYP2J2. We conducted studies of AA metabolism using recombinant CYP enzymes to estimate the inhibition constant and the type of inhibition by telmisartan of CYP2C9 and CYP2C8. The contribution ratio (CR) of each CYP enzyme was investigated using human liver microsomes. Dixon and Lineweaver-Burk plots indicated that telmisartan is a mixed inhibitor of both CYP2C9 and CYP2C8; telmisartan did not show a time-dependent inhibition toward these CYP enzymes. Based on the CRs, both CYP2C9 and CYP2C8 are the key enzymes in the metabolism of AA in the human liver. Uptake of telmisartan in the liver by organic anion transporting polypeptide (OATP) 1B3 and the non-linear metabolism in gastrointestinal tract augment the potential of the drug to inhibit the CYP enzymes in the liver.

High Frequency of Acute Adverse Cardiovascular Events After Lung Transplantation in Patients With Pulmonary Arterial Hypertension Receiving Preoperative Long-Term Intravenous Prostacyclin.

Adverse cardiovascular events after lung transplantation (LT) increase the mortality in patients with pulmonary arterial hypertension (PAH). Long-term intravenous prostacyclin is the usual treatment in severe patients with PAH, but it may increase the risk of hemorrhage due to its antiplatelet aggregation effect or thrombocytopenia. We investigated the impact of length of intravenous prostacyclin therapy on acute adverse cardiovascular events including hemorrhagic complication after LT. We retrospectively compared the incidence of adverse events (death, intrathoracic hematoma and bleeding, cardiac congestion or shock, cerebral infarction and pulmonary embolism) within 30 days after LT between no/short-term (median 0.6 years, n = 13) and long-term (median 3.7 years, n = 15) intravenous prostacyclin groups. There were no differences in the dose of intravenous prostacyclin and pulmonary artery pressure between the two groups. Among 22 adverse events (0.8 ± 1.1 events/patient), 4 events occurred in the no/short-term intravenous prostacyclin group and 18 occurred in the long-term intravenous prostacyclin group. The event rate per patient in the long-term intravenous prostacyclin group (1.2 ± 1.3 events/patient) was significantly higher than that in the no/short-term intravenous prostacyclin group (0.3 ± 0.5 events/patient) (P < 0.05). Intrathoracic hematoma and bleeding was the most frequent adverse event (9 events, 41%). Preoperative long-term intravenous prostacyclin therapy increases acute adverse cardiovascular events after LT in patients with PAH.

Antioxidative and Inhibitory Effects of the Fruiting Body of Black Lingzhi Mushroom, Amauroderma rugosum (Agaricomycetes), on LDL Oxidation and HMG-CoA Reductase Activity.

Amauroderma rugosum fruiting bodies possess excellent cardiovascular benefits, including antioxidative, antihyperlipidemic, antihypertensive, antiinflammatory, anti-platelet aggregation, and antithrombotic effects. In this article, we describe our investigations of the in vitro antioxidant activity and in vitro antiatherosclerotic potential through inhibitory effects on low-density lipoprotein (LDL), LDL peroxidation, and 3-hydroxy3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalytic activity using various fruiting body extracts partitioned with an organic solvent. Among 5 extracts/fractions tested, the semipolar ethyl acetate (EA) fraction demonstrated good antioxidant capacity based on total phenolic content, 2,2-diphenyl-1-picrylhydrazyl free radical scavenging, ferrous ion-chelating ability, cupric ion-reducing antioxidant capacity, and lipid peroxidation assays. The EA fraction also showed the strongest inhibitory effect on Cu2+-induced LDL oxidation via thiobarbituric acid reactive substances formation and HMG-CoA reductase activity. Chemical analysis conjointly identified 10 phenolic compounds (4 benzoic acid derivatives, 3 flavonoids, 1 cinnamic acid, 1 hexahydroxydiphenic acid dilactone, and 1 xanthone derivative), some of which play pivotal roles in arresting the physiopathogenesis of atherosclerosis, thereby attenuating the risk of cardiovascular events occurring.

Real world analysis to explore clinical features of Shenxiong glucose injection combined with other medications

To explore the real world clinical medication and combination characteristics of Shenxiong glucose injection. The basic information of patients with Shenxiong glucose injection, traditional Chinese and western medicine diagnosis information, doctor advice information and laboratory test information from the hospital information system(HIS) of 19 tertiary hospitals in China. Apriori algorithm was adopted to establish the models, and Clementine 12.0 was used for correlation analysis to analyze the real world clinical medication and combination characteristics of Shenxiong glucose injection. Among 8 316 patients in the study, 523 kinds of western medicine and 148 kinds of traditional Chinese medicine(TCM) were used. In combined application, the single western medicine with highest use frequency was aspirin(1 908 cases, 22.94%), and single Chinese medicine with highest use frequency was Shuxuetong injection (771 cases, 9.27%); the most common TCM pair was Xianling Gubao capsule+Lugua Duotai injection(rules support degree was 2.55%), and the most common western medicine pair was aspirin+atorvastatin(degree of association rules was 10.15%). They were often used in combination with antibiotics, blood-activating and stasis-dissolving prescription, and adrenal cortical hormone drugs. Shenxiong glucose injection was often used in combination with antiplatelet drugs and blood-activating and stasis-dissolving prescription in clinical application to enhance the effects of anti-platelet aggregation and blood-activating and stasis-dissolving; it was often used in combination with antibiotics to treat cor pulmonale, and incompatibility shall be noticed to ensure efficacy enhancement under the premise of clinical medication safety.

Effects of extracts and isolated compounds from safflower on some index of promoting blood circulation and regulating menstruation

Ethnopharmacological relevanceCarthamus tinctorius is used as one of the Traditional Chinese Medicine (TCM) materials in prescriptions and composite to promote blood circulation to remove blood stasis, regulate menstruation and alleviate pain for over 2500 years. Modern pharmacological experiments have demonstrated that safflower has wide-reaching biological activities, including dilating coronary artery, modulating immune system, improving myocardial ischemia, anticoagulation and thromboprophylaxis, antioxidation, antihypoxic, antiaging, antifatigue, antiinflammation, anti-hepatic fibrosis, antitumor, analgesia, etc. Materials and methodsPlatelet aggregation of safflower extract and main constituents in safflower were determined by PAF-induced or ADP-induced platelet aggregation in vitro. Anticoagulation activity was measured by clotting assay of thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) according to the methods provided by the biological reagents provider (Sun Biochemical). Antioxidant effects of safflower were assessed using DPPH radical-scavenging activity test, ABTS radical-scavenging activity test and ferric reducing antioxidant power test. In addition, rats ovary granulosa cell proliferation activity was used for the bio-activity index on regulate menstruation of safflower. ResultsSafflower extract at the concentration of 0.7g/mL (P<0.001) and 0.5g/mL (P<0.01) had significantly antagonistic effect on PAF-induced platelet aggregation, compared with negative control. And the anti-platelet aggregation of 0.7g/mL safflower extract was significantly stronger than that of positive control (P<0.001). 0.7g/mL of hydroxysafflor yellow A (P<0.01), anhydrosafflor yellow B (P<0.05), 6-hydroxykaempferol-3-O-rutinoside (P<0.05), keampferol-3-O-β-rutinoside (P<0.01) had significant effect on platelet aggregation compared with negative control. Safflower extract at the concentration of 0.5g/mL (P<0.001) and 0.125g/mL (P<0.01) could significantly inhibit ADP-induced platelet aggregation, compared with negative control. And antagonistic effect of safflower extract was significantly stronger than the effect of positive control (P<0.001). Adenosine (P<0.001), anhydrosafflor yellow B (P<0.01) and 6-hydroxykaempferol-3-O-rutinoside (P<0.01) at the concentration of 0.5g/mL had significant effect on ADP-induced platelet aggregation compared with negative control. 0.125g/mL of adenosine (P<0.05) had significant effect on ADP-induced platelet aggregation compared with negative control. The effect of 0.5g/mL adenosine (P<0.01) and 6-hydroxykaempferol-3-O-rutinoside (P<0.05) was significantly stronger than that of positive control. Safflower extract at the concentration of 0.7mg/mL (P<0.001) and 0.5mg/mL (P<0.001) had significantly anticoagulation activity in PT, TT and APTT, compared with negative control. However, the respective compound didn’t have significant effect on PT and TT at experiment concentration. At the concentration of 0.7mg/mL, hydroxysafflor yellow A (P<0.01), 6-hydroxykaempferol-3,6,7-tri-O-β-d-glucoside (P<0.05), 6-hydroxyapigenin-6-O-glucoside-7-O-glucuronide (P<0.01), anhydrosafflor yellow B (P<0.001), 6-hydroxykaempferol-3-O-rutinoside (P<0.05) and keampferol-3-O-β-rutinoside (P<0.05) significantly prolonged APTT, compared with negative control. At the concentration of 0.5mg/mL, hydroxysafflor yellow A (P<0.05), 6-hydroxyapigenin-6-O-glucoside-7-O-glucuronide (P<0.05), anhydrosafflor yellow B (P<0.001), 6-hydroxykaempferol-3-O-rutinoside (P<0.05) and keampferol-3-O-β-rutinoside (P<0.05) could significantly prolong APTT, compared with negative control. From the results of DPPH, ABTS radical scavenging activity test and Fe3+ reduction power test, 5mg/mL, 2.5mg/mL and 1.25mg/mL safflower extract had antioxidant effects. Every compound with each concentration (5mg/mL, 2.5mg/mL and 1.25mg/mL) had significant effect on Fe3+ reduction power (P<0.001 vs. negative control). Safflower extract, cytidine, 6-hydroxy-kaempferol-3,6-di-O-β-d-glucoside-7-O-β-d-glucuronide, 6-hydroxykaemp-ferol-3,6,7-tri-O-β-D-glucoside and keampferol-3-O-β-rutinoside significantly promoted ovarian granulosa cell proliferation. ConclusionBased on previous researches, the activities of safflower extract and pure compounds isolated from safflower were studied in this paper. This study found some compounds with the effects of anti-platelet aggregation, anticoagulation, antioxidation and ovarian granulosa cell proliferation, and further revealed the possible pharmacological mechanism of safflower.

Evaluation of Changes in Bleeding Time in Hypertensive Patients on Amlodipine - A Prospective Observational Study

International Journal of Pharmacology and Clinical Sciences,2016,5,2,45-48.DOI:10.5530/ijpcs.5.2.2Published:June 2016Type:Research ArticlesAuthors:Pallavi Mahadeva Kamath, Suresh Surappla Rudrappa, Arun Suresh, Narendranath Sanji, Shashikala Gowdara Hanumanthareddy, and Imran Maniyar Author(s) affiliations:Pallavi Mahadeva Kamath1, Suresh Surappla Rudrappa2, Arun Suresh1, Narendranath Sanji3, Shashikala Gowdara Hanumanthareddy4, Imran Maniyar1 1Postgraduate, Department of Pharmacology, JJM Medical College, Davanagere, Karnataka, INDIA. 2Assistant Professor, Department of Medicine, JJM Medical College, Davanagere, Karnataka, INDIA. 3Associate Professor, 4Professor and Head, Department of Pharmacology, JJM Medical College, Davanagere, Karnataka, INDIA. Abstract:Background: Platelet hyperactivity is a risk factor in hypertensive patients that paves the way to atherothrombosis causing cardiovascular and cerebrovascular events. Counteracting platelet aggregation is an established step in preventing thrombotic events. Calcium channel blockers are one among the recommended antihypertensive agents according to 2013 ESH/ESC (European Society of Hypertension and European Society of Cardiology) guidelines. In addition to lowering blood pressure they are known to have antiplatelet activity. Dihydropyridine class of L-type calcium channel blockers are the most potent group and shares this activity. Anti-platelet aggregatory effect of these agents could supplement its anti-hypertensive property and could prove to be desirable in the treatment of hypertensives with high risk of atherosclerotic and thromboembolic risk. So the present study aims to explore the anti-platelet activity of Amlodipine. Objectives: To evaluate the anti-platelet activity of Amlodipine in hypertensive patients. Methods and Materials: Sixty subjects were enrolled in the study. Test group comprised of thirty patients with essential hypertension, who were prescribed Tab Amlodipine at doses 5 mg or 10 mg once daily orally. Patients included in study group were regularly on Amlodipine for at least one month. 30 normotensive subjects, who are not on any drug affecting platelet function like Aspirin, dipyridamole, statins etc. acted as control group.Duke method of Bleeding time estimation was used to assess changes in Bleeding time. Statistical analysis: Student’s unpaired t-test was used to compare Amlodipine test group with the normotensive control group. Results were expressed as Mean bleeding time ± SEM. SPSS software version 20 was used for statistical calculations. Results: The mean bleeding time of Amlodipine group was 2.214 minutes ± 0.028 SEM. The control group had a mean bleeding time of 1.998 minutes ± 0.036 SEM. The result gave a statistically significant p value of <0.001. Average duration of treatment was 3.683 years. Conclusion: The statistically significant bleeding time observed in Amlodipine group suggest that it has anti-platelet activity. Keywords:Amlodipine, Antiplatelet activity, Bleeding time, HypertensionView:PDF (404.2 KB) PDFClick here to download the PDF file. Images Bar diagram representing Mean BT ± SEM of Amlodipine and Control

New urushiols with platelet aggregation inhibitory activities from resin of Toxicodendron vernicifluum

Eight new urushiol-type compounds (1–7b), along with seven known compounds were isolated from the resin of Toxicodendron vernicifluum Stokes. Their structures were determined by extensive spectroscopic methods, included 1H NMR, 13C NMR, HMQC, HMBC, HRESIMS, EI-MS in combination with CD methods. All the compounds except 7a and 7b were evaluated for their anti-platelet aggregation activities in vitro. Among them, compound 5 (IC50=5.12±0.85μmol/L), with a vic-diol moiety in the long alkyl chain showed the most potent inhibitory of platelet aggregation activity induced by ADP. In addition, compound 6 showed the effect of anti-platelet aggregation induced by AA with the IC50 value of 3.09±0.70μmol/L. Thus, these compounds might be the active components to the traditional use of Resina Toxicodendri for breaking up blood stasis, which could be related to the anti-platelet aggregation.

A novel selective inhibitor to thrombin-induced platelet aggregation purified from the leech Whitmania pigra

Background/aimThe dried whole body of the leech Whitmania pigra, a well-known traditional Chinese medicine, has been widely used to treat thrombus diseases for thousands of years. However, its bioactive constituents were reported rarely. The aim of our study was to investigate antithrombotic components of it. MethodsThe antithrombotic peptide was purified using a combination of anion-exchange chromatography, ultrafiltration and reverse-phase HPLC. the sequence of the peptide was determined using MALDI-TOF-MS-MS. Anti-platelet aggregation activity in vitro was evaluated using a turbidimetric method, and antithrombotic effect in vivo was assessed in an arterio-venous shunt thrombosis model in rats. ResultsA novel antithrombotic peptide named WP-30, with the sequence VISRTQSNVQAAWGQVGGHAADYSAVAIER, was isolated from the dried whole body of the leech W. pigra. WP-30 selectively inhibited thrombin-induced anti-platelet aggregation in vitro, and potently attenuated thrombus formation in rats in vivo. ConclusionsTaken together, we found a novel peptide from leech bodies, and this peptide showed antiplatelet aggregation and antithrombotic effects.

Preparation and Physicochemical and Pharmacokinetic Characterization of Ginkgo Lactone Nanosuspensions for Antiplatelet Aggregation

The aim of this study was to investigate the potential of nanosuspensions (NSs) in improving the dissolution and absorption of poorly water-soluble ginkgo lactones (GLs), including ginkgolide A, ginkgolide B, and ginkgolide C. Liquid GL-NSs were prepared by a combined bottom-up and top-down approach with response surface methodology design, followed by freeze-drying solidification. Physicochemical characterization of the prepared freeze-dried GL-NSs was performed by photon correlation spectroscopy, scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. In vitro dissolution and in vivo bioavailability of ginkgolide A, ginkgolide B, and ginkgolide C in freeze-dried GL-NSs were evaluated with GLs coarse powder as control. Their inhibitory effects on platelet aggregation were also comparatively analyzed. GLs existed in an amorphous state in the prepared freeze-dried GL-NSs. The particle size, polydispersity index, zeta potential, and redispersibility index of freeze-dried GL-NSs were around 286 nm, 0.26, −25.19 mV, and 112%, respectively. The particle size reduction resulted in much more rapid and complete dissolution of ginkgolides from GL-NSs than coarse powder. Comparison with GLs coarse powder, freeze-dried GL-NSs showed a significant decreased Tmax, 2-fold higher peak concentration, and 2-fold higher area under plasma concentrations curve for 3 ginkgolides and exhibited significantly higher antiplatelet aggregation effect.

Anti-platelet aggregation bioassay based quality control for XST capsules

A in vitro platelet aggregation bioassay was developed for the quality control of XST capsules. The in vitro anti-platelet aggregation effect in rats was observed to detect the bioactivity of XST capsules. Panax notoginseng saponins and Xuesaitong lyophilizedpowder for injection were taken as standard control substances to determine the potency. According to the results, XST capsules showeda significant inhibitory effect on thrombin-induced platelet aggregation in a dose-dependent manner. The in vitro anti-platelet activity oflyophilized powder for injection was stabler than that of Panax notoginseng saponins, and so suitable to serve as a standard control substance. The biological potency of XST capsules compared with standard control substance was detected by using parallel line assay. According to the results, the established bioassay method had a good repeatability (RSD 2.92%). The sample test results could pass thereliability test(linear deviation P > 0.05, parallel deviation P > 0.05). This bioassay method could be used as one of the complementary quality control methods for XST capsules.