Design, synthesis and antiplatelet aggregation activity of 3-acetyl-7-hydroxycoumarin derivatives / 中国药科大学学报

@#Abstract: In order to search for coumarin-based anti-platelet aggregation compounds with high efficacy and good druggability, twenty-five 3-acetyl-7-hydroxy-coumarin oxime derivatives (6a-6y) were synthesized via Vilsmeier-Haack reaction, Knoevenagel reaction, Williamson reaction, electrophilic substitution reaction and oximation reaction from resorcinol. Their structures were confirmed by HRMS and 1H NMR spectra. The anti-platelet aggregation activity of the target compounds was evaluated using Born’s turbidimetric method. The results revealed that most of them could significantly inhibit platelet aggregation induced by adenosine diphosphate (ADP), collagen, arachidonic acid (AA) and thrombin. Among them, the target compounds 6a and 6b not only had strong inhibitory activity on platelet aggregation induced by the four inducers, but also exhibited good water solubility (3.46 mg/mL and 3.85 mg/mL, respectively) and lipid-water partition coefficient (2.56 and 2.85, respectively) and were expected to become a preclinical candidate compound with multi-target action against platelet aggregation.

Valor Prognóstico da Escore PRECİSE DAPT em Resultados de Curto e Longo Prazo em Pacientes MINOCA com Síndrome Coronariana Aguda / Prognostic Value of PRECİSE DAPT Score on Short- and Long-Term Outcomes in MINOCA Patients with Acute Coronary Syndrome

Resumo Fundamento O infarto do miocárdio com artérias coronárias não obstrutivas (MINOCA) constitui um subconjunto significativo de infartos agudos do miocárdio (IAM) com marcadores prognósticos incertos. A avaliação precoce do risco é crucial para identificar pacientes MINOCA em risco de resultados adversos. Objetivos Este estudo teve como objetivo avaliar a capacidade preditiva do escore PRECISE-DAPT na avaliação do prognóstico de curto e longo prazo em pacientes MINOCA que apresentam infarto do miocárdio sem supradesnivelamento do segmento ST (IAMSSST) ou com supradesnivelamento do segmento ST (IAMCSST). Métodos Entre 741 pacientes MINOCA, o escore PRECISE-DAPT foi calculado para analisar sua associação com eventos cardiovasculares adversos maiores (MACE) intra-hospitalares e de acompanhamento. Os parâmetros que apresentaram significância nos grupos MACEM (+) foram submetidos à análise estatística: regressão logística univariada para eventos intra-hospitalares e regressão univariada de Cox para eventos de seguimento. Para significância estatística, foi adotado nível pré-definido de α = 0,05. Os parâmetros que demonstraram significância foram submetidos à regressão logística múltipla para eventos intra-hospitalares e à regressão multivariada de Cox para eventos de seguimento. Resultados Os MACE intra-hospitalares ocorreram em 4,1% dos pacientes, enquanto 58% apresentaram MACE no acompanhamento. Os níveis de hemoglobina e o escore PRECISE-DAPT foram identificados como parâmetros independentes para MACE intra-hospitalar. Além disso, a fração de ejeção (FE%) e o escore PRECISE-DAPT surgiram como preditores independentes de MACE no acompanhamento. Conclusões O estudo revelou que um escore PRECISE-DAPT mais alto foi significativamente associada a riscos aumentados de eventos cardiovasculares adversos maiores tanto intra-hospitalares quanto de longo prazo em pacientes MINOCA que apresentam síndrome coronariana aguda (SCA), ressaltando o potencial do escore na estratificação de risco para esta coorte de pacientes.

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) constitutes a significant subset of acute myocardial infarctions (AMI) with uncertain prognostic markers. Early risk assessment is crucial to identify MINOCA patients at risk of adverse outcomes. Objectives This study aimed to evaluate the predictive capacity of the PRECISE-DAPT score in assessing short- and long-term prognoses in MINOCA patients presenting with ST-segment elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). Methods Among 741 MINOCA patients, the PRECISE-DAPT score was computed to analyze its association with in-hospital and follow-up major adverse cardiovascular events (MACE). Parameters showing significance in MACE (+) groups underwent statistical analysis: univariate logistic regression for in-hospital events and univariate Cox regression for follow-up events. For statistical significance, a predefined level of α = 0.05 was adopted. Parameters demonstrating significance proceeded to multiple logistic regression for in-hospital events and multivariate Cox regression for follow-up events. Results In-hospital MACE occurred in 4.1% of patients, while 58% experienced follow-up MACE. Hemoglobin levels and the PRECISE-DAPT Score were identified as independent parameters for in-hospital MACE. Furthermore, ejection fraction (EF%) and the PRECISE-DAPT Score emerged as independent predictors of follow-up MACE. Conclusions The study revealed that a higher PRECISE-DAPT score was significantly associated with increased risks of both in-hospital and long-term major adverse cardiovascular events in MINOCA patients presenting with acute coronary syndrome (ACS), underscoring the score's potential in risk stratification for this patient cohort.

Real-world clinical experience of ticagrelor in Indian patients with acute coronary syndrome after discharge from a tertiary setting

Background: To understand the usage pattern of ticagrelor in real-life clinical experience in Indian patients with the acute coronary syndrome (ACS) after discharge from a tertiary care setting. Methods: A retrospective multicentric observational study conducted across Indian healthcare centers having medical records of adult patients with ACS. Patients prescribed with ticagrelor post-discharge for at least 1 month were included. The study endpoints were to determine the clinical effectiveness of ticagrelor in post-ACS patients and adverse events reported during the study period. Results: A total of 1910 patients with ACS with a mean (SD) age of 58.2 (11.3) years were enrolled in this study. The median (IQR) duration of treatment was 30.0 (30.0-90.0) days. More than half of the patients (n=1115, 58.4%) were managed with interventional therapy. The most common comorbid conditions were type-2 diabetes mellitus (46.9%), followed by hypertension (36.8%). A total of 9.7% of patients reported complaints after treatment with ticagrelor. Among them, weakness, giddiness, and body pain were the most common (3.2%). Conclusions: This real-world study revealed that ticagrelor had been used widely in patients who underwent different management strategies. History of diabetes and hypertension were the most common risk factors. There were no major adverse events reported during the follow-up, indicating ticagrelor is well-tolerated in Indian patients with ACS.

High on-treatment platelet reactivity in patients with ischemic stroke or transient ischemic attack / 国际脑血管病杂志

Antiplatelet drugs are the cornerstone of long-term treatment and secondary prevention for ischemic stroke/transient ischemic attack (TIA) recommended by guidelines, aimed at reducing the risk of recurrent stroke and other cardiovascular events. However, some patients with ischemic stroke/TIA may still experience ischemic events during antiplatelet therapy, known as high on-treatment platelet reactivity (HTPR), which typically occurs in patients taking aspirin or clopidogrel. This article elaborates the incidence, risk factors, and commonly used evaluation methods of HTPR in patients with ischemic stroke/TIA, and elucidates the clinical significance of HTPR in patients with ischemic stroke/TIA, and investigates the antiplatelet treatment protocol of patients with HTPR.

De-escalação de inibidores dos receptores P2Y12 após intervenção coronária percutânea / P2Y12 inhibitor de-escalation after percutaneous coronary interventions

Em pacientes que apresentam síndromes coronárias agudas e são tratados com intervenção coronária percutânea, a prescrição do esquema antiplaquetário duplo, composto de ácido acetilsalicílico e um inibidor dos receptores P2Y12, é mandatória, contribuindo para a redução de eventos cardíacos maiores. No entanto, ao mesmo tempo em que previne eventos isquêmicos, essa associação pode precipitar complicações hemorrágicas maiores, o que é mais comumente observado quando são prescritos os medicamentos mais potentes, como o prasugrel ou o ticagrelor. Essas constatações levaram à procura de alternativas terapêuticas capazes de manter a proteção contra eventos isquêmicos e, ao mesmo tempo, prevenir a ocorrência de hemorragias. Uma das estratégias que está em estudo é a de-escalação dos inibidores P2Y12, que consiste no uso dos medicamentos mais potentes numa fase precoce após o procedimento, com substituição deles pelo clopidogrel, após um período de, em geral, 30 dias de evolução; outra possibilidade seria a simples redução da dose do fármaco de maior potência, algo que, até o momento, só pode ser cogitado com o prasugrel. A de-escalação pode ser feita de forma guiada, utilizando testes de mensuração objetiva da agregação plaquetária ou exames para avaliar o perfil genético dos pacientes, ou não guiada, na qual o cardiologista simplesmente faz a substituição ou redução da dose ao fim do período estipulado, sem o auxílio de exames complementares. A literatura contempla ensaios clínicos com essas duas opções de estratégia, os quais são discutidos nesta revisão. Até o momento, nenhuma diretriz médica recomenda de forma explícita o uso regular dessa alternativa terapêutica.

In patients who have acute coronary syndromes and are treated with percutaneous coronary intervention, the prescription of a dual antiplatelet regimen, consisting of acetylsalicylic acid and a P2Y12 receptor inhibitor, is mandatory, contributing to the reduction of major cardiac events. However, while preventing ischemic events, this association may precipitate major bleeding complications, which is more commonly seen when more potent drugs, such as prasugrel or ticagrelor, are prescribed. These findings led to the search for therapeutic alternatives that could maintain the protection against ischemic events and, at the same time, prevent the occurrence of hemorrhages. One of the strategies being studied is de-escalation of P2Y12 inhibitors, which consists of the use of more potent drugs in an early phase after the procedure, replacing them with clopidogrel, after a period of, in general, 30 days of clinical course. Another possibility would be to simply reduce the dose of the most potent drug, which so far can only be considered with prasugrel. De-escalation can be done in a guided way, using objective measuring tests of platelet aggregation or exams to assess the genetic profile of patients, or unguided, in which the cardiologist simply replaces or reduces the dose at the end of the stipulated period, with no ancillary tests. The literature includes clinical trials with these two strategy options, which are discussed in this review. So far, no medical guideline explicitly recommends the regular use of this therapeutic alternative.

Effect of Anti?Platelet Therapy on Peri?Operative Blood Loss in Patients Undergoing Off?Pump Coronary Artery Bypass Grafting

Purpose:The purpose of this study was to review the effect of the pre?operative use of clopidogrel and aspirin on peri?operative bleeding, blood product transfusion, and resource utilization after coronary artery bypass grafting (CABG). Materials and Methods: A total of 1200 patients who underwent off?pump CABG (OPCABG) between 2010 and 2012 were retrospectively studied. Patients were divided into three groups: group 1: discontinued aspirin and clopidogrel 6 days prior to surgery (n = 468), group 2: discontinued both drugs 3 to 5 days prior to surgery (n = 621), and group 3: discontinued both drugs 2 days prior to surgery (n = 111). The bleeding pattern and blood product transfusion were studied and compared between the groups. Patients having history of other drugs affecting the coagulation profile, other organ dysfunction, on?pump CABG, and the combined procedure were excluded from the study. Results: Group 2 patients had a higher rate of bleeding and a reduced mean value of hemoglobin (Hb) as compared to other groups. The same results were seen in blood and blood product transfusion. Patients of group 2 and group 3 were associated with higher blood loss in terms of drainage at 12 and 24 hours. Post?operatively, this was statistically significant. Re?exploration was statisitically significant in group 3 patients (9.01%) than in group 2 (2.58%) and group 1 (1.07%) patients. Conclusion: The pre?operative use of clopidogrel and aspirin in patients undergoing OPCABG showed limited clinical benefits; however, its use significantly increased the risk of bleeding and blood transfusion, thus increasing morbidity and resource utilization. Hence, clopidogrel and aspirin should be stopped at least 6 days prior to surgery.

Platelet Aggregation on Glass Surface under Physiological Flow Condition / 医用生物力学

Objective To investigate platelet aggregation on glass surface under physiological flow condition. Methods The polydimethylsiloxane (PDMS)-glass microchannel chips were fabricated by soft lithography. Anti-coagulant human peripheral whole blood was flowed through the microchannel chip at flow shear rate of 300 s-1 and 1 500 s-1, respectively. The fluorescence images of platelet aggregates formed on glass surface at the bottom of the microchannel were captured after 150 s using an inverted fluorescence microscope. The number of platelet aggregates, average size, surface coverage and average fluorescence intensity were quantified by image analysis. The glass surface was treated with oxygen plasma, BSA blocking or collagen modification to establish different surfaces for platelet aggregation. The hematocrit (Hct) of blood sample was adjusted, and the whole blood was treated with different anti-platelet agents. The platelet aggregation on glass surface was observed under the above experimental conditions. The platelet aggregations in healthy people and diabetic patients were also analyzed. Results Under the flow condition, platelet aggregation on glass surface was three-dimensional. Platelet aggregation was dependent on wall shear rate, the hydrophilicity of glass surface and Hct, and was mainly regulated by GPIIb/IIIa-fibrinogen and ADP-P2Y12 receptor pathways. The aggregation of platelets on the glass surface could also reflect the high activity of platelets in diabetic patients. Conclusions At the flow conditions of 300 s-1 and 1 500 s-1, platelet aggregation on glass surface is related to flow rate, protein adsorption, platelet related receptors and platelet activation state. In this study, a new model for microfluidic platelet function analysis without additional adhesion protein modification was established, and it could be used for clinical evaluation of platelet function.

Novedades de las guías de la Sociedad Europea de Cardiología 2020 sobre manejo del síndrome coronario agudo sin elevación persistente del segmento ST / News from the European Society of Cardiology 2020 guidelines on the management of acute coronary syndrome without persistent ST-segment elevation / Novidades da Sociedade Europeia de Cardiologia 2020 diretrizes sobre o tratamento da síndrome coronariana aguda sem elevação persistente do segmento ST

Las enfermedades cardiovasculares representan la primera causa de muerte en el mundo. El manejo de los síndromes coronarios ha avanzado formidablemente en los últimos 50 años, reduciendo el riesgo isquémico, a expensas del consiguiente aumento del riesgo hemorrágico. La Sociedad Europea de Cardiología publicó en el año 2020 la guía sobre el manejo de síndrome coronario agudo sin elevación del segmento ST, donde se destacan cambios en los algoritmos de estratificación de riesgo y la terapia antiplaquetaria y anticoagulante como dos de los aspectos principales. En el presente editorial se resumen las principales novedades publicadas en este documento.

Cardiovascular disease is the leading cause of death worldwide. The management of coronary syndromes has advanced dramatically in the last 50 years, reducing ischemic risk, but observing an increase in bleeding risk. The European Society of Cardiology published in 2020 the guideline on the management of acute coronary syndrome without ST-segment elevation, where changes in risk stratification algorithms and antiplatelet and anticoagulant therapy are highlighted as two of the main aspects. This editorial summarizes the main developments published in this document.

A doença cardiovascular é a principal causa de morte em todo o mundo. O manejo das síndromes coronarianas avançou dramaticamente nos últimos 50 anos, reduzindo o risco isquêmico, mas observando um aumento no risco de sangramento. A Sociedade Europeia de Cardiologia publicou em 2020 a diretriz sobre o manejo da síndrome coronariana aguda sem supradesnivelamento do segmento ST, onde as alterações nos algoritmos de estratificação de risco e na terapia antiplaquetária e anticoagulante são destacadas como dois dos principais aspectos. Este editorial resume os principais desenvolvimentos publicados neste documento.

Dual antiplatelet therapy for mild stroke and transient ischemic attack / 国际脑血管病杂志

Patients with mild stroke and transient ischemic attack (TIA) have a high risk of early recurrence or deterioration. Antiplatelet therapy has been recognized to reduce the risk of ischemic vascular events. All guidelines recommend antiplatelet therapy for patients with ischemic stroke. Dual antiplatelet therapy (DAPT) refers to the application of two drugs with different mechanisms to block platelet aggregation and prevent thrombosis. There are many combinations of DAPT, and its safety and effectiveness are still uncertain. This article reviews the efficacy and safety of DAPT in patients with mild stroke and TIA.

The clinical profile of patients with intracerebral hemorrhage after receiving acute coronary syndrome regimen in a tertiary hospital: A case series

@#Coronary heart disease, which includes acute coronary syndromes (ACS) is a major cause of death and morbidity. Treatment for this condition includes dual anti-platelet treatment combined with an anti-coagulant and an anti-dyslipidemic. Bleeding complications may occur and one fatal adverse event is intracerebral hemorrhage (ICH). ACS cases in a tertiary hospital for the years 2014-2018 showed that there were 7 patients who presented with symptomatic ICH after treatment administration that accounts for 0.01% of a total of 1,097 patients. These patients were over the age of 50, but with no sex predilection. Common comorbidities were hypertension and malignancy. All patients presented with acute onset neurologic deficits within 1-4 days after administration of ACS regimen, with ICH scores of 3-4 signifying a high mortality rate of 72-90%. 6 out 7 patients had significant volume of ICH with mass effects, and 1 with subarachnoid hemorrhage. This lead to poor outcome in all patients with 6 out of 7 mortalities and 1 left with substantial disability. It was found that given the total number of patients administered with the said treatment, there is a low incidence of ICH.

Effect of anti-platelet antibodies on the efficacy of immunoglobulin therapy and Treg/Th17 ratio in children with immune thrombocytopenia / 中国输血杂志

【Objective】 To investigate the relationship between anti-platelet antibodies, therapeutic effect of intravenous immunoglobulin (IVIG) and Treg/Th17 cells imbalance in children with immune thrombocytopenia (ITP). 【Methods】 The changes and correlation of platelet count and Treg/Th17 ratio before and after IVIG treatment in 60 newly diagnosed ITP children with anti-platelet antibodies and 60 children with primary ITP without anti-platelet antibodies were analyzed. 【Results】 1) Compared with the control group, the efficacy of IVIG treatment was better in children with ITP in the case group(CR+ R cases: 50 vs 32) (P<0.01). 2) After IVIG treatment, platelet count(×109/L)(case: 4.5±2.9 vs 327.4±69.5, control: 4.1±3.2 vs 304.7±75.9), Treg cell level(%)(case: 2.15±1.08 vs 5.09±1.37, control: 2.41±0.92 vs 4.98±1.10), Treg/Th17 ratio(case: 1.10±0.19 vs 7.75±1.11, control: 1.27±0.21 vs 4.69±0.81)significantly increased while Th17 cell level(%) significantly decreased in the 2 groups of children(case: 2.07±1.31 vs 1.37±0.92, control: 2.13±1.18 vs 1.48±1.01); compared with the control group, there was no significant change in Treg, Th17 and Treg/Th17 ratio before and after treatment in the case group (P>0.05), but platelet count increased more significantly (P<0.05). 3) There were 3 positive cases in the control group and 12 negative cases in the case group after IVIG treatment, and IVIG treatment probably had no effect on the positive rate of anti-platelet antibodies in children with ITP (P>0.05). 4) The change in platelet count after IVIG treatment was significantly positively correlated with Treg levels (r=0.49 in the case group and r=0.441 in the control group) and negatively correlated with Th17 cell levels (r=-0.390 in the case group and r=-0.364 in the control group). 【Conclusion】 Anti-platelet antibodies can be used as a predictor of the efficacy of IVIG therapy in children with ITP, but they are not associated with changes in the Treg/Th17 ratio.

Prevalence of CYP2C19 gene mutations in patients with coronary heart disease and its biological activation effect in clopidogrel antiplatelet response / 中华心血管病杂志

Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.

Analysis of the efficacy of tirofiban in the treatment of transient ischemic attack with high risk of recurrence / 中风与神经疾病杂志

@#Objective　To investigate the efficacy of tirofiban on transient ischemic attack with high risk of recurrence.Methods　156 patients with non-cardiogenic transient ischemic attack with ABCD2 score ≥ 4 points were hospitalized at the Department of Neurology,Sinopharm Tongmei General Hospital from Jan 2019 to Mar 2021.Eight patients were excluded due to incomplete data or drop-off from follow-up.The remaining 148 patients were randomly divided into two groups,78 in the observation group and 70 in the control group.The observation group was given tirofiban treatment (loading tirofiban via a micropump,and continuous intravenous pumping for 48 hours) and intensive lipid-lowering therapy.The control group was given intensive anti-platelet aggregation therapy with Aspirin enteric-coated tablets,hydroclopidogre and intensive lipid-lowering therapy.We made a comparative analysis between two groups about efficacy,safety and short-term stroke incidence.Results　In the observation group,57 cases were cured,14 cases were effective,and 7 cases were ineffective;6 cases (7.69%) had a stroke (cerebral infarction) within 7 days,7 cases (8.97%) had a stroke within 30 days,and 7 cases (8.97%) had a stroke within 90 days.In the control group,39 cases were markedly effective,15 cases were effective,and 16 cases were ineffective;in the control group,13 cases (18.57%) had a stroke (cerebral infarction) within 7 days,15 cases (21.43%) had a stroke within 30 days,16 cases (22.86%) had a stroke within 90 days.No intracerebral hemorrhage occurred in either group within 90 days.The two groups had statistical significance in terms of effective treatment rate (P<0.05).However,there was no significant difference in the number of stroke cases between the observation group and the control group in the short-term 7 days,30 days,and 90 days (P>0.05).There was no significant difference in coagulation,platelet,liver and kidney function between the two groups after 48 hours of treatment (P>0.05).Conclusion　For patients with transient ischemic attack at high risk of recurrence,tirofiban treatment can effectively control TIA attacks,but it cannot reduce the risk of stroke.

Review of studies on Bulbine natalensis Baker (Asphodelaceae): Ethnobotanical uses, biological and chemical properties

Bulbine natalensis Baker is a native succulent herb that belongs to the family Asphodelaceae, and is regarded asprecious, highly valued, and extensively used throughout the continent for medicinal purposes and in treating maleimpotency due to the aphrodisiac and invigorating effect. This study reviews the status of B. natalensis ethnobotanicaluses, biological and chemical properties. This review was conducted from April 2019 to February 2020 by applyingthe mixed-method review approach, and in the framework of a complete description of B. natalensis species, dataon morphology, distribution, and economic importance were discussed. Pharmacological screening reported thatB. natalensis possesses anti-inflammatory and broad-spectrum antimicrobial properties. The bulbous plant vapourcontains substances such as tannins, anthraquinones, cardiac glycosides, saponins, and alkaloids. Scientific evaluationsfrom various researchers have substantiated the use of B. natalensis in the enhancement of male sexual disorders, cureof wounds, rashes, itches, ringworm, diabetes, rheumatism, cracked lips and herpes, diarrhea, and paroxysms amongother diseases.

Advances in pharmacological effects of higenamine on cardiovascular system / 药学学报

Higenamine (HG) is an active cardiotonic component isolated from Aconite. Chinese and foreign scholars have done a lot of research on the metabolism and pharmacological effects of HG, which confirmed that it has cardiovascular pharmacological effects of cardiactonic action and vasodilation for the treatment of heart failure and bradycardia, anti-oxidative and anti-apoptotic effects which can be used to protect the heart and reduce heart ischemia and reperfusion injury. In addition, HG inhibits the expression of iNOS mRNA by inhibiting the activity of the transcription factor NF-κB, inhibits the lipopolysaccharide (LPS)-induced NO product, and inhibits platelet aggregation and thrombus formation, thereby improving the experimental septic shock in animals. This article reviews the recent progress in cardiovasular pharmacology of HG, which will contribute to the further development and clinical application of it in the future.

Design, synthesis, and neuroprotective and anti-platelet aggregation research of 3-n-butylphthalide derivatives / 药学学报

Butylphthalide and ferulic acid exhibit excellent therapeutic effects in ischemic stroke. In this research, twelve 3-n-butylphthalide derivatives were designed by molecular hybridization strategy. The target compounds were obtained by nucleophilic substitution, reduction reaction, esterification reaction and elimination reaction, and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The compounds with the best neuroprotective activity were biologically evaluated for their ability to inhibit platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) via the Bron method．The results indicate that 7b exhibited potent neurocyte protective activity as well as prominent anti-platelet aggregation activity. Compound 7b has potential to be developed as a drug for ischemic stroke.

Design, synthesis, and biological evaluation of ligustrazine/resveratrol hybrids as potential anti-ischemic stroke agents / 中国天然药物

To search for potent anti-ischemic stroke agents, a series of tetramethylpyrazine (TMP)/resveratrol (RES) hybrids 6a-t were designed and synthesized. These hybrids inhibited adenosine diphosphate (ADP)- or arachidonic acid (AA)-induced platelet aggregation, among them, 6d, 6g-i, 6o and 6q were more active than TMP. The most active compound 6h exhibited more potent anti-platelet aggregation activity than TMP, RES, as well as positive control ticlopidine (Ticlid) and aspirin (ASP). Furthermore, 6h exerted strong antioxidative activity in a dose-dependent manner in rat pheochromocytoma PC12 cells which were treated with hydrogen peroxide (HO) or hydroxyl radical (·OH). Importantly, 6h significantly protected primary neuronal cells suffered from oxygen-glucose deprivation/reoxygenation (OGD/R) injury, comparable to an anti-ischemic drug edaravone (Eda). Together, our findings suggest that 6h may be a promising candidate warranting further investigation for the intervention of ischemic stroke.

Anti-platelet aggregation mechanism of Xixian Tongshuan Preparation based on molecular simulation methods / 中国中药杂志

The thrombus is a deposit that is formed on the surface of the endovascular or at the site of repair,and known as the main complication of cardiovascular disease and the cause of death. At the same time,thrombus is mainly treated by the following three ways: anticoagulation,anti-platelet aggregation and thrombolysis. In this study,the chemical constituents of seven traditional Chinese medicines in the Xixian Tongshuan Preparation were collected to construct a component database. Subsequently,the pharmacophore were used to screen out the component database,and molecular docking was used to screen out the results of pharmacophore for explaining the material basis and mechanism that Xixian Tongshuan Preparation exerts anti-thrombotic activity by inhibiting platelet aggregation. First of all,P2 Y12,GPⅡb/Ⅲa and PAR1 were selected as study vectors,the optimal models of inhibitors were obtained respectively through verification and evaluation of the pharmacophore models. Afterwards,the component database was screened out by the optimal pharmacophore models of PAR1,P2 Y12 and GP Ⅱ b/Ⅲ a,and the molecular docking method was used to further refine the screening results. The screening results indicated that the anti-platelet aggregation effect of Xixian Tongshuan Preparation was correlated with the inhibition of P2 Y12,PAR1 and GPⅡb/Ⅲa expressions with saffower yellower,hirudin and candidin and notoginseng triterpenes,folinic acid,respectively. The material basis and mechanism of anti-platelet aggregation of Xixian Tongshuan Preparation provided a theoretical basis for the clinical use of the preparation and the lead compounds for the development of anti-platelet aggregation drugs.

Measurement of antiplatelet aggregation and potency of hirudo / 药学学报

The objective of this work was to develop a bioassay to quantify the antiplatelet aggregation activity of hirudo for quality evaluation and control. Antithrombin activity of hirudo extracted by high temperature decoction was determined by thrombin titration. Antiplatelet aggregation activity of hirudo was determined through pharmacodynamic experiments in vitro and in vivo using a bioassay we developed for quantifying inhibition of platelet aggregation. Methodological investigation was carried out and the titers of 12 batches of hirudo samples were determined. During the experiment, the disposal of animals is in accordance with the ethical standards of animal experiments. The results showed that the antithrombin activity of hirudo decocted at high temperature decreased significantly and almost lost its activity. Hirudo inhibited platelet aggregation and results in vivo and in vitro were consistent. These assays were employed to test 12 batches of hirudo. The results demonstrated that the biopotency of 12 batches was 113.49, 96.13, 121.22, 127.33, 83.48, 108.72, 131.41, 127.95, 76.90, 126.27, 132.89 and 573.53 U·mg-1. The method was reliable and reproducible and can be used to assess the quality of hirudo.

Research Progress in Clopidogrel Resistance / 医药导报

Clopidogrel is one of the anti-platelet drugs, which is widely used in the world.It plays an important role in the treatment of patients with acute coronary syndrome and those undergoing percutaneous coronary intervention.Clopidogrel is effective in inhibiting the activity of platelets, decreasing the incidence of thrombosis in the stent, and then reducing the risk of adverse cardiovascular events in affected individuals. However, some patients still have coronary thrombosis after taking clopidogrel.This phenomenon is known as clopidogrel resistance or clopidogrel non-response or low response. Identification of clopidogrel resistance is of great significance in preventing the occurrence of adverse cardiovascular events.This paper provides guidance for the clinical treatment of clopidogrel resistance by discussing the definition, mechanisms and laboratory evaluation of clopidogrel resistance.