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Objective To develop a pharmacogenomics study of ticagrelor in patients with acute coronary syndrome (ACS), identify the genetic factors that can predict individual differences in antiplatelet aggregation effects of ticagrelor, and provide a reference for the development of individualized regimens for ticagrelor. Methods 75 ACS patients of Chinese Han in a hospital in Fujian province in 2018 who met the entry criteria were recruited. The patient was given the tests for platelet function test, platelet aggregation rate and DNA detection. The whole exon sequencing method (WES) was used to detect the single nucleotide polymorphisms of SLO1B1, UGT2B7, P2Y12, PEAR1, ITGA2B and ITGB3. At the same time, the general clinical data of the patients were collected and recorded. The correlation between antiplatelet aggregation effects of ticagrelor and pharmacogenetic polymorphism was analyzed by one-way analysis of variance, multiple linear regression analysis and binary logistic regression analysis. Results One-way analysis of variance showed that SLCO1B1 rs2306283 mutant allele G could affect the antiplatelet aggregation effect of ticagrelor, the average platelet aggregation rate of patients carrying at least one allele G (AG+GG type) was significantly lower than that of wild homozygotes AA patients (8.07%±6.17% vs 13.88%±6.39%, P≤0.05). However, multivariate regression analysis after adjusting for confounding factors showed that SLCO1B1 rs2306283 mutant allele G was not an independent variable affecting the antiplatelet effects of ticagrelor (P>0.05). Conclusion Single nucleotide polymorphisms of genes related to ticagrelor transport receptors, targets, and platelet membrane receptors (including SLO1B1, UGT2B7, P2Y12, PEAR1, ITGA2B, ITGB3) in ACS patients of Han Chinese in Fujian province will not significantly affect the antiplatelet aggregation effect of ticagrelor, which provides a new treatment option for patients with genetic defects who are not suitable for clopidogrel.
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Ischemic cerebrovascular disease (ICVD) is the most common type of nervous system disease in clinical practice in China at present. It is the important leading cause of death after heart disease and tumors. Ischemic cerebrovascular disease has a high rate of occurrence and mortality. It is easy to cause problems such as limb dysfunction, language disorders, nerve dysfunction, etc. It has a great negative effect on the quality of life of patients, and seriously affects the quality of their lives. Although the current research on the treatment of the disease has achieved certain results, single therapies can only treat some key parts of the disease and cannot completely reverse the whole process. At present, thrombolysis, antiplatelet aggregation, degradation of plasma fibrin, anticoagulation, and hemodilution are mainly used in clinical treatment. It is critical to select appropriate treatment methods based on the pathological characteristics of patients to improve efficacy and prognosis. In this review, the research progress in therapies for ischemic cerebrovascular disease was reviewed, both at home and abroad.
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Aim To study the mechanism of anti-plate- let aggregation of sorghum root active parts. Methods The effects of active fraction (WEAE-M 30%) from sorghum roots on platelet aggregation induced by collagen, thrombin and adenosine diphosphate were investigated in vitro. Western blot, enzyme-linked immunoas-say, flow cytometry and fluorescence techniques were used to explore the mechanism of the antiplatelet aggregation effect of WEAE-M 30% . Results WEAE-M 30% had a significant inhibitory effect on platelet aggregation induced by the three agonists mentioned above. The inhibitory effect on platelet aggregation induced by collagen was the most significant, with an inhibitory rate of (72. 91 ±2. 42)%. It was found that WEAE-M 30% had a significant inhibitory effect on the collagen- mediated platelet (IPVI signaling pathway protein Src, MAPK signaling pathway protein p38 and ERK phosphorylation. It also significantly inhibited the levels of ATP, P-selection and Ca2+ in platelets. Conclusions It is suggested that the mechanism of WE-AE-M 30% antiplatelet aggregation may be related to the inhibition of platelet activation pathway GPV1, MAPK and the release of typical platelet representative particles.
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Objective: To establish a biological potency assay for Xiaojin Pills against platelet aggregation in vitro, evaluate the quality consistency of Xiaojin Pills, and screen traditioanal Chinese medicines which play the role of promoting blood circulation in Xiaojin Pills. Methods: Xiaojin Pills and ten Chinese medicines [artificial musk, Momordica cochinchinensis, Aconitum kusnezoffii, Liquidambar formosana, Boswellia carterii, Commiphora myrrha, Faeces Trogopterori, Angelica sinensis, Pheretima aspergillum, Fragrant Ink] in its formula were extracted by ultrasound in 40% methanol. The antiplatelet aggregation rate of the extract was measured by platelet aggregation meter. The platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were prepared from abdominal aorta of rats. The platelet aggregation was induced by adenosine diphosphate (ADP). With sodium ferulate as a standard reference material, the biological potency of antiplatelet aggregation of Xiaojin Pills was calculated by the simplified probit principle. Results: The results showed that the biological potency of Xiaojin Pills was between 0.598 and 1.338 U/mg among different manufacturers and batches. In Xiaojin Pills group, Pheretima, Faeces Trogopterori, and Momordicae Semen had stronger inhibitory effects on platelet aggregation with inhibition rates of 70.87%, 31.83% and 67.52%, respectively. Conclusion: The quality consistency of Xiaojin Pills from different manufacturers and batches is poor, and Pheretima, Faeces Trogopterori, and Momordicae Semen may be the key drugs for Xiaojin Pills to play the role of promoting blood circulation.
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Xiaojin pills, the first choice for clinical treatment of breast hyperplasia, were selected to explore the suitability of a bioactivity assay with chemical fingerprinting for the development of an overall quality evaluation assay. The liposoluble and water-soluble fraction fingerprints of Xiaojin pills were established. The ability to inhibit platelet aggregation and the rate of inhibition of cyclooxygenase-2 (COX-2) for 16 batches of Xiaojin pills from several manufacturers was analyzed; the chemical fingerprints of these samples were correlated with the bioactivity and chemical analysis. The animal protocol was approved by the Committee on the Ethics of Animal Experiments of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Approval, ID: 2018BL-002. Results showed that the antiplatelet aggregation activity of 16 batches was 0.712-1.278 U∙mg-1, with a relative standard deviation (RSD) of 15.4%. COX-2 inhibition was 52.07%-68.95% and the RSD was 8.91%. The results showed that there was little difference in the biological effects of these samples. However, the chemical fingerprint consistency of these 16 batches of Xiaojin pills was poor, and the similarity of nearly half of the samples was less than 0.9. The total peak area of Xiaojin pills was 32.74%-165.37% across samples, showing very poor chemical consistency. In order to explore the reasons for the poor chemical consistency despite good consistency in the biological assays, the fingerprint chromatogram was analyzed by multivariate statistical analysis. The main chromatographic peaks were identified. The results showed that the similarity of Xiaojin pills was mainly determined by the prominent chromatographic peaks 17, 18, 20, 23 and 27 in the liposoluble fingerprints, which were identified from Liquidambaris resina and Angelica sinensis Radix. However, Liquidambaris resina and Angelicae sinensis Radix had almost no anti-platelet aggregation activity or COX-2 inhibitory effect at the normal prescription ratio. As a result, the ability to utilize chemical fingerprints to evaluate the quality consistency of Xiaojin pills is limited. The selection of biological evaluation methods that reflect clinical efficacy could make up for the shortcomings of chemical evaluation methods for quality assessment, and provide new ideas and methods for the overall quality evaluation of complex Chinese patent medicines.
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Objective: To clarify the active constituents of the heartwoods of Caesalpinia sappan, a traditional Chinese medicine with the functions of promoting blood circulation (Huoxue in Chinese) and removing blood stasis (Quyu in Chinese). Methods: The chemical constituents were isolated and purified by combination of silica gel and Sephadex LH-20 column chromatography, along with semipreparative HPLC. Their chemical structures were established by multiple spectroscopic methods and comparison with literature data. The in vitro antiplatelet aggregation activities were evaluated using mouse platelet induced by AYPGKF-NH2, a gold agonist of protease-activated receptor 4 (PAR4). Results: Two new phenols, methyl 2-(4,4′,5′-trihydroxy-2′-(methoxymethyl) biphenyl-2-yloxy) acetate (1) and 1′-methylcaesalpin J (2), together with 24 known compounds (3–26), were isolated from the heartwoods of C. sappan. Among them, sappanchalcone (16) and brazilin (20) showed inhibitory activities against mouse platelet aggregation with IC50 values of 114.8 µmol/L and 100.8 µmol/L, respectively. Conclusion: Antiplatelet compounds from C. sappan targeting at PAR4 are reported for the first time.
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<p><b>OBJECTIVE</b>To detect the anticoagulation and antiplatelet effects of different concentrations of puerarin, heparin sodium and tirofiban hydrochloride on the blood samples of healthy volunteers by Sonoclot coagulation and platelet function analyzer.</p><p><b>METHODS</b>Peripheral blood samples were extracted from 20 healthy volunteers, followed by adding different concentrations of puerarin, heparin sodium and tirofiban hydrochloride. Samples were detected for activated clotting time (ACT), clot rate (CR) and platelet function (PF) by Sonoclot coagulation and platelet function analyzer instrument.</p><p><b>RESULTS</b>For puerarin and heparin sodium, the values of ACT gradually increased, and the values of CR and PF gradually decreased with increasing in drug concentration. There was a linear (or log linear) relationship between ACT, CR, PF value and drug concentration (P<0.01). Corresponding to each value, a regression equation was obtained. For tirofiban hydrochloride, the values of ACT and CR had no significant changes, while PF values gradually decreased with concentration increasing. There was also a linear relationship between PF values and concentrations of tirofiban hydrochloride (P<0.01). Under the same ACT values, the puerarin corresponding CR values (CR = e, P<2.2e-16) were always higher than the corresponding values (CR = e, P-value<2.2e-16) of heparin sodium. For high concentrations of puerarin (e.g. 3.8 mg/600 μL) and tirofiban hydrochloride (e.g. 0.8 μg/600 μL), PF values had no significant difference. However, PF values for high puerarin concentration had a larger variance.</p><p><b>CONCLUSIONS</b>Puerarin has similar anticoagulant and antiplatelet effects with the heparin sodium, and may have a lower hemorrhage risk than heparin sodium when obtained the same anticoagulation effect in the concentration range of this experiment. In addition, for high concentration, puerarin had the same antiplatelet function as tirofiban hydrochloride but with a larger individual variability.</p>
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Objective: To develop a bioassay method to quantify the antiplatelet aggregation bioactivity (AAB) of crude Chuanxiong Rhizoma, decotion pieces, and its Chinese patent medicine for quality assessment. Methods: Chuanxiong Rhizoma sample was extracted in water by reflux. The level of AAB in extract was quantified in vitro. The blood was taken from the heart of rabbit. The platelet aggregating in platelet-rich plasma was induced by adenosine-5'-diphosphate disodium salt. The ratio of platelet inhibition was chosen as AAB marker. Sodium ferulate was a reference. The amount of AAB in aqueous extract was quantified by the Amount reaction of parallel line analysis (2.2) method. The AAB data of herbal sample was calculated by combining the AAB of extract with its extraction rate. Moreover, AAB amounts were quantified in the eight samples including crude Chuanxiong Rhizoma, decoction pieces, and Chinese patent medicines to verify this developed method. Results: Both sodium ferulate and Chuanxiong extract showed significant AAB (P < 0.01). The reliability test for quantifying AAB in solidum ferulate and Chuanxiong Rhizoma extract was passed through, and the measured value was valid. The correlation coefficient was 0.993 4 (n = 4) between the amounts of solidum ferulate in the concentration range of 15-60 mg/mL and their ratios of platelet inhibition. The RSD for the amounts of AAB was 3.43% (n = 6) by six replicated tests with the confidence limit rate of 23.90% (n = 6). The AAB amounts were significantly different among tested samples, i.e. 3.183, 2.068, 1.957, and 1.931 U/g for four Chuanxiong Rhizoma crude samples, 1.304 and 1.021 U/g for Chuanxiong Rhizoma decotion pieces and processed slice with yellow wine, 0.506 and 0.919 U/g for Suxiao Jiuxin Pills and Lemai Granule. Conclusion: The developed method can accurately quantify the level of AAB in Chuanxiong Rhizoma crude, decoction pieces, and Chinese patent medicines, which can be used to assess the product quality of Chuanxiong Rhizoma.
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Objective: To explore the active components of antiplatelet aggregation of Erigeron breviscapus, chemical fingerprints and bioactivity detection were used to carry out spectrum-effect correlation analysis. Methods: A fingerprinting method was established by ultra-high performance liquid chromatography with ultraviolet detection (UPLC-UV) and then used for fingerprinting of different batches of E. breviscapus. The antiplatelet aggregation biopotency of different batches of E. breviscapus was tested, and the possible active substances were deduced based on spectrum-effect correlation analysis. Furthermore, all five compounds were verified by antiplatelet aggregation in vitro, and the contribution value of relative activity of the five compounds was calculated according to the difference of the contents of five kinds of monomer compounds in E. breviscapus. Results: Through the spectrum-effect correlation analysis of chemical fingerprints and antiplatelet aggregation biopotency of E. breviscapus, five chromatographic peaks with higher bioactivity correlation coefficient were screened and identified, including chlorogenic acid, caffeic acid, scutellarin, isochromic acid A, and ischlorogenic acid C. Further in vitro experiments showed that the five compounds had different levels of antiplatelet aggregation at same concentration (inhibition rate: 16.5%-85.5%). The sequence of the relative activity contribution is scutellarin > ischlorogenic acid C > caffeic acid > ischlorogenic acid A > chlorogenic acid. In terms of activity contribution of five compounds, chlorogenic acid C and scutellarin was larger than other compounds. Conclusion: A method for the determination of antiplatelet aggregation biopotency of E. breviscapus in vitro was established. Moreover, scutellarin and ischlorogenic acid C are the main active substances of E. breviscapus in the aspect of antiplatelet aggregation in vitro.
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Objective The double antiplatelet therapy with aspirin and clopidogrel is widely used in the progressive stroke patients.However, this therapeutic regimen is still lack of guideline confirmation .In this study, we aimed to observe the effects of cere-bral hemodynamics and platelet parameters of combined antiplatelet treatment with aspirin and clopidogrel on progressive stroke patients . Methods This retrospective study enrolled 82 patients with progres-sive stroke within 24 hours in the Nanjing Brain Hospital Affiliated to Nanjing Medical University from January 2014 to January 2016.All the patients were divided into two groups ( single antiplatelet group and combined antiplatelet group ) according to the antiplatelet therapy .Forty patients were included in the single antiplatelet group oral-ly took aspirin 0.1g once a day while in the combined antiplatelet group forty-two patients were included to take clopidogrel 75 mg once a day besides aspirin for 21 days and then kept aspirin only .All the patients were observed for 3 months.On the 1st and 7th day of ad-mission and 3 months after admission , the patients were examined for the terms of the grades of National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI), as well as the platelet parameters including plaletet count (PLT), thrombocytocrit (PCT), mean platelet volume ( MPV) and platelet distribution width ( PDW) .The thrombelastogram was done to test the plate inhibition rate . Meanwhile , the transcranial doppler examination was done to realize the cerebral hemodynamics . Results After 7 days'and 3 months'treatment, the grades of NIHSS of combined antiplatelet group were significantly decreased versus single antiplatelet group , while BI of the combined antiplatelet group was significantly increased ( P<0.05 ) .The inhibition rate induced through adenosine diphosphate pathway was higher in the combined antiplatelet group versus the single antiplatelet group (P=0.003) on the 7th day.PLT ( P=0.006) level in the combined antiplatelet group was higher than that in the single antiplatelet group , while MPV ( P=0.023) and PDW (P=0.017) were actually lower in the combined antiplatelet group than the single antiplatelet group after 7 days'treatment.After 3 months, PDW in the combined antiplatelet group was still lower than the single antiplatelet group (P=0.041).On the 7th day, Vs (P=0.046), Vm (P=0.039) in bilateral middle cerebral artery in the combined antiplatelet group were lower than the single anti -platelet group.After 3 months, the Vs (P=0.030), PI (P=0.041) in the combined antiplatelet group was further improved versus the single antiplatelet group . Conclusion The improved effects of combined antiplatelet treatment with aspirin and clopidogrel on the clinical symptoms, cerebral hemodynamics and platelet parameters were better than single antiplatelet treatment with aspirin .
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Objective The double antiplatelet therapy with aspirin and clopidogrel is widely used in the progressive stroke patients.However, this therapeutic regimen is still lack of guideline confirmation .In this study, we aimed to observe the effects of cere-bral hemodynamics and platelet parameters of combined antiplatelet treatment with aspirin and clopidogrel on progressive stroke patients . Methods This retrospective study enrolled 82 patients with progres-sive stroke within 24 hours in the Nanjing Brain Hospital Affiliated to Nanjing Medical University from January 2014 to January 2016.All the patients were divided into two groups ( single antiplatelet group and combined antiplatelet group ) according to the antiplatelet therapy .Forty patients were included in the single antiplatelet group oral-ly took aspirin 0.1g once a day while in the combined antiplatelet group forty-two patients were included to take clopidogrel 75 mg once a day besides aspirin for 21 days and then kept aspirin only .All the patients were observed for 3 months.On the 1st and 7th day of ad-mission and 3 months after admission , the patients were examined for the terms of the grades of National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI), as well as the platelet parameters including plaletet count (PLT), thrombocytocrit (PCT), mean platelet volume ( MPV) and platelet distribution width ( PDW) .The thrombelastogram was done to test the plate inhibition rate . Meanwhile , the transcranial doppler examination was done to realize the cerebral hemodynamics . Results After 7 days'and 3 months'treatment, the grades of NIHSS of combined antiplatelet group were significantly decreased versus single antiplatelet group , while BI of the combined antiplatelet group was significantly increased ( P<0.05 ) .The inhibition rate induced through adenosine diphosphate pathway was higher in the combined antiplatelet group versus the single antiplatelet group (P=0.003) on the 7th day.PLT ( P=0.006) level in the combined antiplatelet group was higher than that in the single antiplatelet group , while MPV ( P=0.023) and PDW (P=0.017) were actually lower in the combined antiplatelet group than the single antiplatelet group after 7 days'treatment.After 3 months, PDW in the combined antiplatelet group was still lower than the single antiplatelet group (P=0.041).On the 7th day, Vs (P=0.046), Vm (P=0.039) in bilateral middle cerebral artery in the combined antiplatelet group were lower than the single anti -platelet group.After 3 months, the Vs (P=0.030), PI (P=0.041) in the combined antiplatelet group was further improved versus the single antiplatelet group . Conclusion The improved effects of combined antiplatelet treatment with aspirin and clopidogrel on the clinical symptoms, cerebral hemodynamics and platelet parameters were better than single antiplatelet treatment with aspirin .
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@#A series of hydrogen sulfide-releasing derivatives of open ring 3-n-butylphthalide(5a-5f)were designed, synthesized, and their structures were confirmed by MS and 1H NMR. The inhibitory activity of the target compounds against adenosine diphosphate(ADP)and arachidonic acid(AA)-induced platelet aggregation was evaluated in vitro by Born′s turbidimetric assay. In comparison with 3-n-butylphthalide(NBP), compound 5e possessed better antiplatelet aggregation activity. Therefore, it may be utilized as a lead compound for further investigation.
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Objective To evaluate the feasibility of application of single and dual antiplatelet aggregation therapy in high sensitive C-reactive protein (hs-CRP) level in patients with angina pectoris. Methods Ninety-six hospitalized patients with angina 6~48 h (hs-CRP0.05). There were no significant differences in events of composite end points in patients after treatment between two groups (P > 0.05). Conclusion For angina pectoris patients with hs-CRP<2 mg/L, the risk of cardiovascular events is relatively little. There is no obvious difference in curative effect between single and dual antiplatelet aggreration therapies.
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This study was aimed to investigate the dose-response relations and synergy effects of bioactive components in Ginkgo bilobaon antiplatelet aggregation and DPPH free radical scavenging.The antiplatelet aggregation experiment and DPPH free radical scavenging experiment were conducted respectively to investigate the dose-response relations and synergy effects.Firstly,the effect of inhibiting platelet aggregation induced by PAF of ginkgolides in rabbits was investigated.And then,the effect of DPPH free radical scavenging by ginkgo flavonoids was also investigated.Finally,the synergy effects among effective components were studied.The results showed that ginkgolide A,ginkgolide B,ginkgolide C and bilobalide had dose-response relations on antiplatelet aggregation.Quercetin,kaempferol and isorhamnetin had DPPH free radical scavenging effects with dose-response relation.It was concluded that ginkgolide had the dose-response relation on antiplatelet aggregation.Ginkgolide A and ginkgolide B had synergy effect.Ginkgo flavonoids had DPPH free radical scavenging effect.Quercetin and isorhamnetin had synergy effect.
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OBJECTIVE: To construct a library of the multi-components of Radix Paeoniae Sinjiangensis and explore the methods for its separation and characterization.
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We compared antiobese, hypocholesterolemic, antiplatelet and antioxidant effect of 10% green tea powder and 3% green tea extract in rats pair fed 5% cholesterol diets. The final body weight was decreased significantly compared with the control (p < 0.05). Plasma and liver total cholesterol were lower in group of green tea powder or extract, but not statistically different. HDL cholesterol was increased significantly in group of green tea powder compared with the control or green tea extract (p < 0.05). Plasma triglyceride was significantly decreased in group of green tea extract compared with green tea powder, and green tea powder compared with the control respectively (p < 0.05). Liver triglyceride was significantly decreased in group of green tea powder or green tea extract compared with the control (p < 0.01). Platelet aggregations in the maximum and initial slope were not different among groups. Hemolysis was significantly lower in group of green tea powder compared with the control (p < 0.05). Plasma TBARS production was decreased in group of green tea extract compared with the control (p < 0.05). Na passive leak in intact cells was not different, but Na leak in AAPH treated cell was significantly decreased in group of green tea powder than the control (p < 0.05). The leak increase (delta Na Leak) after AAPH treatment was significantly decreased in groups of green tea powder and extract compared with the control (p < 0.05). Isotope excretion after 14C-cholesterol ingestion was significantly increased in group of green tea extract compared with the control or the green tea powder (p < 0.05). Consumption of green tea in powder or extract may give beneficial effects in weight control and plasma lipid profiles, impeding metabolic syndrome. More studies are needed to clarify what component of green tea and what mechanism are involved in antiobese and hypolipedemic actions of green tea.
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Animals , Rats , Amidines , Antioxidants , Blood Platelets , Body Weight , Cholesterol , Cholesterol, HDL , Diet , Eating , Hemolysis , Lipid Peroxidation , Liver , Plasma , Tea , Thiobarbituric Acid Reactive Substances , Weight GainABSTRACT
AIM: To study the blood quickening and stasis dispelling effect of the different processed products of Rhizoma Curcumae by rat's platelet aggregation in vivo and its hemorrheological properties and blood coagulation. METHODS: The platelet aggregation determination, hemorrheological properties determination and mice blood coagulation method were used to observe the blood quickening and stasis dispelling effect of the different processed products of Rhizoma Curcumae. RESULTS: The different processed products of Rhizoma Curcumae all had some inhibition on platelet aggregation, anticoagulation and improvement on the hemorrheological parameters. Among all of them, the processed product with vinegar was the most strong. CONCLUSION: In traditional processes, pharmacological test shows that Rhizoma Curcumae processed with vinegar has the best effects.