Qilong capsule prevents myocardial ischemia/reperfusion injury by inhibiting platelet activation via the platelet CD36 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Qilong capsule (QC) is developed from the traditional Chinese medicine formula Buyang Huanwu Decoction, which has been clinically used to invigorate Qi and promote blood circulation to eliminate blood stasis. Myocardial ischemia‒reperfusion injury (MIRI) can be attributed to Qi deficiency and blood stasis. However, the effects of QC on MIRI remain unclear. AIM OF THE STUDY: This study aimed to investigate the protective effect and possible mechanism of QC on platelet function in MIRI rats. MATERIALS AND METHODS: The left anterior descending artery of adult Sprague‒Dawley rats was ligated for 30 min and then reperfused for 120 min with or without QC treatment. Then, the whole blood viscosity, plasma viscosity, coagulation, platelet adhesion rate, platelet aggregation, and platelet release factors were evaluated. Platelet CD36 and its downstream signaling pathway-related proteins were detected by western blotting. Furthermore, the active components of QC and the molecular mechanism by which QC regulates platelet function were assessed via molecular docking, platelet aggregation tests in vitro and BLI analysis. RESULTS: We found that QC significantly reduced the whole blood viscosity, plasma viscosity, platelet adhesion rate, and platelet aggregation induced by ADP or AA in rats with MIRI. The inhibition of platelet activation by QC was associated with reduced levels of ß-TG, PF-4, P-selectin and PAF. Mechanistically, QC effectively attenuated the expression of platelet CD36 and thus inhibited the activation of Src, ERK5, and p38. The active components of QC apparently suppressed platelet aggregation in vitro and regulated the CD36 signaling pathway. CONCLUSIONS: QC improves MIRI-induced hemorheological disorders, which might be partly attributed to the inhibition of platelet activation via CD36-mediated platelet signaling pathways.

Tea polyphenol-derived nanomedicine for targeted photothermal thrombolysis and inflammation suppression.

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine's potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.

Integrating network pharmacology with microRNA microarray analysis to identify the role of miRNAs in thrombosis treated by the Dahuang Zhechong pill.

BACKGROUND: Thrombotic diseases are the leading causes of death worldwide, urging for improvements in treatment strategies. Dahuang Zhechong pill (DHZCP) is a traditional Chinese medicine widely used for treating thrombotic diseases; however, the underlying mechanisms remain unclear. This study aimed to explore the potential mechanisms of DHZCP in treating thrombosis with a focus on bioinformatics and miRNAs. METHODS: We used network pharmacology to explore the targets of thrombosis treated with DHZCP and performed microarray analysis to acquire miRNA profiles and predict the target genes in thrombin-stimulated MEG-01 cells treated with DHZCP. Based on the overlapping of targets, we carried out a component-target-miRNA network and enrichment analysis and validated the selected miRNAs and mRNAs using quantitative reverse transcription-polymerase chain reaction. RESULTS: Our data showed 850 targets of 230 active ingredients of DHZCP and 1214 thrombosis-related genes; 235 targets were common. We identified 32 miRNAs that were regulated by thrombin stimulation but regulated reversely by DHZCP treatment in MEG-01 cells, and predicted 1846 targets with function annotation. We analyzed conjointly 23 integrating targets from network pharmacology and microarray. HIF1A, PIK3CA, MAPK1 and BCL2L1 emerged as key nodes in the network diagrams. We confirmed the differential expression of seven miRNAs, one mRNA (BCL2L1) and platelet surface protein. CONCLUSIONS: This study showed that miRNAs and their targets, such as BCL2L1, played crucial roles in platelet activation during DHZCP intervention in thrombosis, highlighting their potential to alleviate platelet activation and increase cell apoptosis. The study's findings could help develop new strategies for improving thrombosis treatment.

Elucidating the distinctive regulatory effects and mechanisms of active compounds in Salvia miltiorrhiza Bunge via network pharmacology: Unveiling their roles in the modulation of platelet activation and thrombus formation.

Salvia miltiorrhiza Bunge. (DS), as an important traditional Chinese medicine (TCM), has a long history of usage for promoting blood circulation and removing blood stasis. Modern studies have shown that the chemical components of DS have many biological activities such as cardiovascular protection, anti-arrhythmia, anti-atherosclerosis, improvement of microcirculation, protection of myocardium, inhibition and removal of platelet aggregation. Nevertheless, the action mechanism of DS as well its active compounds on platelet activation has not been fully uncovered. This study aimed to find out the potential targets and mechanisms of DS in the modulation of platelet activation and thrombosis, using network pharmacology and biological experimental. These compounds with anti-thrombotic activity in DS, cryptotanshinone (CPT), isoeugenol (ISO) and tanshinone IIA (TSA), together with the corresponding targets being Src, Akt and RhoA are screened by network pharmacology. We confirmed that ISO, CPT and TSA dose-dependently inhibited platelet activation in vitro, mainly by inhibiting agonist-induced clot retraction, aggregation and P-selectin and ATP release. The western blot findings indicated that ISO, CPT, and TSA led to reduced levels of p-Akt and p-ERK in activated platelets. Additionally, ISO and TSA were observed to decrease p-cSrc expression while increasing RhoA expression. ISO, CPT, and TSA demonstrated a potential to restrict the advancement of carotid arterial thrombosis in vivo. We confirm that ISO, CPT and TSA are the key anti-thrombotic active compounds in DS. These active compounds exhibit unique inhibitory effects on platelet activation and thrombus formation by modulating the Akt/ERK and cSrc/RhoA signaling pathways.

No effect of omega-3 polyunsaturated fatty acid supplementation on inflammatory markers in familial hypercholesterolemia: a randomized crossover trial.

Individuals with familial hypercholesterolemia (FH) have increased cardiovascular risk despite lipid-lowering therapy, and additional therapy is warranted. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplements have demonstrated an effect on cardiovascular endpoints in some clinical trials. Platelet-modifying and anti-inflammatory properties are among the proposed beneficial effects of n-3 PUFA. We investigated the effect of a high-dose n-3 PUFA supplement on platelet function and inflammatory markers in FH subjects. We performed a randomized, double-blind trial with a crossover design. Inclusion criteria were genetically verified heterozygous FH, stable disease, statin treatment >12 months, and age 18-75 years. Trial participants were allocated to two treatment periods in random order. The treatment periods (three months each) were separated by a three-month washout period. N-3 PUFA (1840 mg eicosapentaenoic acid and 1520 mg docosahexaenoic acid) and placebo (olive oil) were administered in four capsules daily. Endpoints were platelet function and inflammatory markers, assessed by platelet function analyzer, soluble markers P-selectin, vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM), 27 cytokines, and hematological parameters. Thirty-four heterozygous FH individuals completed the trial. No treatment effect (p = 0.93) from n-3 PUFA on the platelet function analyzer was found (2 s, 95% CI [-13, 6]). In our FH population, n-3 PUFA did not influence the levels of P-selectin (-2.0, 95% CI [-5.0, 2.0], p = 0.41), VCAM (0, 95% CI [-14.2, 14.2], p > 0.99), ICAM (-27.0, 95% CI [-70.1, 16.5]; p = 0.21), cytokine levels, or hematological parameters. In statin-treated FH individuals, high dose n-3 PUFA supplement did not affect platelet function and inflammatory markers.Trial registration number: EUDRACTNR 2012-000505-68; ClinicalTrials.gov NCT01813006HighlightsTrial studying the effect of omega-3 fatty acids supplements in familial hypercholesterolemia.High-dose omega-3 fatty acids supplements had no impact on platelet function.Cytokine levels were unchanged after three months of omega-3 fatty acid supplementation.No effect of omega-3 fatty acids on C-reactive protein was observed.

Study on the Relationship between Platelet Activation and TCM Syndrome Distribution in Patients with Diabetic Peripheral Neuropathy / 浙江中医药大学学报

[Objective]To investigate the relationship between platelet activation and traditional Chinese medicine(TCM)syndrome distribution in patients with diabetic peripheral neuropathy(DPN).[Methods]A total of 188 DPN patients admitted to our hospital from February 2020 to December 2022 were collected.The TCM syndrome type usesd the index cluster analysis to draw the cluster diagram.The correspondence between TCM syndrome type and lesion degree was analyzed by simple correspondence analysis,and shown on the two-dimensional plan.It compared the general clinical data,platelet parameters and platelet activation of different TCM syndrome types,so as to explore the relationship between platelet activation and the distribution of TCM syndrome types.[Results]The syndrome types summarized in different positions of the cluster map were different.Among them,D-point interception could be divided into five syndrome types:Qi deficiency syndrome,Yin deficiency syndrome,Yang deficiency syndrome,stagnation of blood stasis syndrome and phlegm-dampness blocking collaterals syndrome.Among the 188 DPN patients,phlegm-dampness blocking collaterals syndrome was found in 18 cases(9.57％),stagnation of blood stasis syndrome in 53 cases(28.19％),Yang deficiency syndrome in 28 cases(14.89％),Yin deficiency syndrome in 39 cases(20.74％),and Qi deficiency syndrome in 50 cases(26.60％).The grade of DPN lesion was grade Ⅰ in 56 cases(29.79％),grade Ⅱ in 76 cases(40.43％),and grade Ⅲ in 56 cases(29.79％).The syndrome of phlegm-dampness blocking collaterals and stagnation of blood stasis in the middle of the two-dimensional projection map did not deviate to a certain grade of DPN lesion degree;Yang deficiency syndrome inclined to grade Ⅲ,Yin deficiency syndrome to grade Ⅱ,and Qi deficiency syndrome to grade Ⅰ.Compared with Qi deficiency syndrome,platelets(PLT),mean platelet volume(MPV),platelet distribution width(PDW),granular membrane protein-140(GMP-140),platelet activating factor(PAF)and E26 transformation specific-l(ETS-l)in patients with Yin deficiency syndrome and Yang deficiency syndrome were significantly higher(P＜0.05),and PLT,MPV,PDW,GMP-140,PAF and ETS-1 in patients with Yang deficiency syndrome were higher than those of Yin deficiency syndrome(P＜0.05).[Conclusion]DPN can be routinely divided into five basic syndrome types:Qi deficiency,Yin deficiency,Yang deficiency,stagnation of blood stasis and phlegm-dampness blocking collaterals.With the development of DPN,TCM syndromes are transformed from Qi deficiency to Yin deficiency to Yang deficiency,while blood stasis and phlegm-dampness blocking collaterals are accompanied by various stages of DPN patients.In the progress of DPN,platelet activation may be involved in the transformation of TCM syndrome types.

Hypericum perforatum and Its Potential Antiplatelet Effect.

BACKGROUND: Hypericum perforatum (HP) is currently one of the most consumed medicinal plants in the world. In traditional Chinese medicine, the herb hypericum (Guan Ye Lian Qiao) belongs to the group of plants that clarify heat. It is also used to treat various types of infection and inflammation. In contrast to the extensive literature on the antidepressant effects of HP, little is known about its action on platelets. The main objective of this work was to investigate the possible relevance of HP to platelet function. METHODS: We characterized the profile of platelet activation in the presence of HP extracts through an evaluation of molecular markers by flow cytometry: mobilization of intracellular Ca++ and expression of platelet receptors such as activated GPIIbIIIa and P-selectin (CD62). RESULTS: The results indicated a possible inhibitory effect of HP on the platelet activation response, which could be explained by the effect on intracellular calcium mobilization and the expression of activated GPIIbIIIa receptors. Despite of the limitations of an in vitro study, our results provide evidence of the possible mechanisms of action of HP. CONCLUSIONS: Further studies are needed to elucidate the effect of HP on hemostasis, but it may be recognized as a substance with antiplatelet properties.

Identification of linoleic acid as an antithrombotic component of Wenxin Keli via selective inhibition of p-selectin-mediated platelet activation.

Atrial fibrillation significantly increases the risk of thromboembolism and stroke. Wenxin Keli (WXKL) is a widely used Chinese patent medicine against arrhythmia but if it has antithrombotic activity is unknown. Since platelet activation is a critical factor in thrombosis and the key target for many antithrombotic drugs, this study aims to demonstrate the antithrombotic efficacy of WXKL. In vitro platelet activation experiments showed that WXKL significantly inhibited platelet adhesion and aggregation. The potential active monomers in WXKL were screened by in silico prediction and in vitro platelet aggregation/adhesion assays. From WXKL chemical fractions and more than 40 monomers, linoleic acid (LA) was identified as the strongest antiplatelet compound. Oral administration of WXKL (1.2 g/kg/day) and LA (50 mg/kg/day) for 7 days significantly improved FeCl3-induced carotid thrombus formation in ICR mice without prolonging bleeding time. Flow cytometry showed that both WXKL and LA inhibited the release of p-selectin after platelet activation. ELISA showed that WXKL and LA also inhibited the expression of 6-Keto-PGF1α in plasma of mice with thrombus, but had no obvious effect on the expression of TXB2. WXKL inhibited platelet activation by broadly inhibiting the phosphorylation of protein kinase B (Akt), mitogen-activated protein kinases (MAPKs) and phospholipase C (PLC) ß3. In contrast, LA only inhibited the phosphorylation of PLCß3. In conclusion, WXKL and its active component LA showed good antiplatelet and antithrombotic efficacy in vivo and in vitro. Mechanistically, the multicomponent Chinese medicine WXKL acts on multiple targets in the platelet activation pathway whereas its active monomer linoleic acid acts specifically on phospholipase C ß3.

The combination of danhong injection plus tissue plasminogen activator ameliorates mouse tail thrombosis-induced by κ-carrageenan.

BACKGROUND: After thrombosis, t-PA thrombolysis is the first choice, but the use of t-PA can easily lead to hemorrhagic injury and neurotoxicity. The combination of Danhong injection (DHI) and tissue plasminogen activator (t-PA) therapy may be a new strategy to find high-efficiency anti-thrombosis and low bleeding risk. However, nothing is about the effect of DHI plus t-PA on platelet activation. PURPOSE: The present research was to explore the optimal dose of DHI and t-PA in vivo and mechanisms involved with the treatment of combining DHI and t-PA for thrombotic disease and determined whether DHI plus t-PA affects thrombotic processes related to platelet activation. METHODS: Mice were induced by administering κ-carrageenan intraperitoneally, the ratio of different doses of DHI and t-PA in vivo, and the optimal dose effects on platelet aggregation, platelet adhesion, thrombosis formation, and platelet activation were determined. The effects of the αIIbß3 signaling pathway were analyzed in mice. RESULTS: In vitro, DHI (62% v/v), t-PA (1 mg/ml), and DHI + t-PA (62% v/v + 1 mg/ml) decreased rat platelet aggregation and adhesion, with a stronger effect from the combination as compared to t-PA monotherapy. In vivo, injections of κ-carrageenan were used to induce BALB/c mice. The optimal dose of DHI, t-PA, and DHI + t-PA is 12 ml/kg, 10 mg/kg, and 12 ml/kg + 7.5 mg/kg. The administration of DHI (12 ml/kg), t-PA (10 mg/kg), and DHI + t-PA (12 ml/kg + 7.5 mg/kg) decreased thrombi in mouse tissue vessels. Furthermore, the reduction of thrombosis formation by DHI, t-PA, and DHI + t-PA was related to lower collagen deposition, and lowered expressions of collagen I, matrix metalloproteinase 2 (MMP-2), and metalloproteinase 9 (MMP-9) in mouse tails, with increased efficacy in combination as compared to t-PA alone. The anti-thrombosis actions of DHI, t-PA, and their combination regulated the expression of CD41, purinergic receptor (P2Y12), guanine nucleotide-binding protein G (q) subunit alpha (GNAQ), phosphatidylinositol phospholipase c beta (PLCß), Ras-related protein 1 (Rap1), RIAM, talin1, fibrinogen alpha chain (FG), kindlin-3, and RAS guany1-releasing protein 1 (RasGRP1). CONCLUSIONS: Based on expression, the mechanism responsible for thrombosis may be attributed to platelet activation via the αIIbß3 signaling pathway. Combination therapy with DHI and t-PA exerted potent thrombolytic effects. Thus, our data can be used as a foundation for further clinical studies examining the efficacy of traditional Chinese medicines for the treatment of thrombosis.

Danshensu prevents thrombosis by inhibiting platelet activation via SIRT1/ROS/mtDNA pathways without increasing bleeding risk.

BACKGROUND: Coronary thrombosis and its correlated disorders are main healthcare problems globally. The therapeutic effects of current treatments involving antiplatelet drugs are not fully satisfactory. Danshensu (DSS) is an important monomer obtained from Salvia miltiorrhiza roots that have been widely employed for vascular diseases in medicinal practices. Nonetheless, the underlying mechanisms of DSS are not fully unraveled. PURPOSE: The objective of this study was to penetrate the antithrombotic and antiplatelet mechanisms of DSS. METHODS: Network pharmacology assay was used to forecast the cellular mechanisms of DSS for treating thrombosis. The work focused the impacts of DSS on platelet activation by analyzing aggregation and adhesion in vitro. Flow cytometry, western blotting, CM-H2DCFDA staining and mitochondrial function assays were performed to reveal the molecular mechanisms. The model of common carotid artery thrombus induced by ferric chloride was established. The wet weight of thrombus was measured, and the thrombosis was observed by hematoxylin and eosin (H&E) staining, in order to support the inhibitory effect of DSS on thrombosis. RESULTS: Data mining found the antithrombotic effect of DSS is related to platelet activation and the core target is silent information regulator 1 (SIRT1). We confirmed that DSS dose-dependently inhibited platelet activation in vitro. DSS was further demonstrated to induce the expression of SIRT1 and decreased reactive oxygen species (ROS) burden and thereby prevented mitochondrial dysfunction. Mitochondrial function tests further indicated that DSS prevented mitochondrial DNA (mtDNA) release, which induced activation of platelet in a dendritic cell specific intercellular-adhesion-molecule-3 grabbing non-integrin (DC-SIGN)-dependent manner. In carotid artery injury model induced by ferric chloride, DSS inhibited the development of carotid arterial thrombosis. More encouragingly, in tail bleeding time assay, DSS did not augment bleeding risk. CONCLUSION: These findings indicated that DSS effectively inhibited platelet activation by depressing the collection of ROS and the release of platelet mtDNA without arousing hemorrhage risk. DSS might represent a promising candidate drug for thrombosis and cardiovascular disease therapeutics.

Dextrose Effects on Platelet Count and Volume: Implications for Regenerative Medicine.

Platelet-rich plasma (PRP) and hypertonic dextrose solutions are commonly used injectates in regenerative medicine, sometimes used simultaneously. The effects of hypertonic dextrose on platelet lysis and activation have not been previously reported. We tested the effects of escalating dextrose concentration on cell counts and cell volume of platelets and red cells in PRP and whole blood (WB). A prompt partial reduction in platelet count occurred with all dextrose admixtures with either PRP or whole blood, consistent with partial lysis. After the first minute, platelet counts remained stable, suggesting a rapid accommodation of residual platelets to extreme (>2000 mOsm) hypertonicity. A 25% or higher dextrose concentration caused a significant increase in mean platelet volume (MPV), which suggests an early phase of platelet activation. Further investigation is warranted to confirm if platelet lysis or activation has occurred and whether additive clinical benefit may result from hypertonic dextrose injection alone or in combination with PRP.

Petasites japonicus extract exerts anti-malarial effects by inhibiting platelet activation.

BACKGROUND: New antimalarial agents are needed to combat emerging resistance to the currently available drugs. In the pathology of cerebral malaria, platelets play a central role by binding infected and uninfected red cells and the endothelium. Since Petasites japonicus extract was reported as an effective inhibitor of platelet activation, we examined the antimalarial activities of the P. japonicus extract. PURPOSE: This study aimed to evaluate the impact of P. japonicus extract prepared from whole plants on malarial infection. METHODS: The P. japonicus extract were characterized by high-performance liquid chromatography (HPLC) profiling. Antimalarial activity of the P. japonicus ethanolic extract was evaluated in vitro using chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) P. berghei strains. Also, the in vivo activity of the extract was evaluated in P. berghei-infected mice via oral administration followed by a four-day suppressive test to measure the hematological parameters. In addition, platelet activation signaling induced by the P. japonicus extract in P. berghei infection was evaluated. RESULTS: In HPLC study, catechin, rutin, liquiritin, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid were identified in P. japonicus extract. Exposure to the P. japonicus extract significantly inhibited both CQ-sensitive (3D7) and resistant (Dd2) strains of P. falciparum with IC50 values of 8.48 ± 1.70 and 7.83 ± 6.44 µg/ml, respectively. Administration of the P. japonicus extract also resulted in potent antimalarial activities in P. berghei-infected mice with no associated toxicity. The treatment also improved the hematologic parameters. In addition, the survived mice from P. berghei infection exhibited the inhibition of collagen-induced platelet aggregation by attenuated glycoprotein VI (GPVI) downstream signaling. CONCLUSION: P. japonicus extracts promote antimalarial effects both in vitro and in vivo. In addition, the effects appear to be induced by the inhibition of collagen-induced platelet activation related to attenuated GPVI downstream signaling. Further studies to identify and characterize the antimalarial compounds in P. japonicus will promote the development of new drugs.

Potential Role of Mitochondria as Modulators of Blood Platelet Activation and Reactivity in Diabetes and Effect of Metformin on Blood Platelet Bioenergetics and Platelet Activation.

Blood platelet dysfunctions are strongly involved in the development of the micro- and macrovascular complications in diabetes mellitus (DM). However, the molecular causes of abnormal platelet activation in DM remain unclear. Experimental data suggests that platelet mitochondria can regulate the prothrombotic phenotype of platelets, and changes in these organelles may influence platelet activation and modify platelet responses to stimulation. The present study evaluates the impact of DM on mitochondrial respiratory parameters and blood platelet activation/reactivity in a rat model of experimental diabetes following 1, 2.5 and 5 months of streptozotocin (STZ)-induced diabetes. Moreover, a mild inhibition of the mitochondrial respiratory chain with the use of metformin under in vitro and in vivo conditions was tested as a method to reduce platelet activation and reactivity. The platelets were studied with a combination of flow cytometry and advanced respirometry. Our results indicate that prolonged exposure of blood platelets to high concentrations of glucose, as in diabetes, can result in elevated blood platelet mitochondrial respiration; this may be an effect of cell adaptation to the high availability of energy substrates. However, as these alterations occur later than the changes in platelet activation/reactivity, they may not constitute the major reason for abnormal platelet functioning in DM. Moreover, metformin was not able to inhibit platelet activation and reactivity under in vitro conditions despite causing a decrease in mitochondrial respiration. This indicates that the beneficial effect of metformin on the coagulation system observed in vivo can be related to other mechanisms than via the inhibition of platelet activation.

Serum proteomic analysis reveals the cardioprotective effects of Shexiang Baoxin Pill and Suxiao Jiuxin Pill in a rat model of acute myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Shexiang Baoxin Pill (SBP) and Suxiao Jiuxin Pill (SJP) are traditional Chinese medicines used to treat cardiovascular disease (CVD) in China. However, the mechanism of their therapeutic effect on CVD has not been clearly elucidated yet. AIMS: The aim of this study is to investigate the cardioprotective effect of SBP and SJP in the treatment of acute myocardial infarction (AMI) model rats by applying serum proteomic approach. MATERIALS AND METHODS: The rat model of AMI was generated by ligating the left anterior descending coronary artery. 42 rats were randomly divided into four groups: sham-operating (Sham, n = 10) group, model (Mod, n = 8) group, Shexiang Baoxin pills pretreatment (SBP, n = 12) group and Suxiao Jiuxin pills pretreatment (SJP, n = 12) group. Data Independent Acquisition (DIA) proteomic approach was utilized to investigate the serum proteome from the rat individuals. The differentially expressed proteins were subsequently obtained with bioinformatic analysis. RESULTS: DIA-MS identified 415 proteins within 42 samples, and 84 differentially expressed proteins may contribute to the therapeutic effects of SBP and SJP. GOBP and KEGG pathway analysis of 84 differentially expressed proteins revealed that the proteins were mainly involved in platelet activation and adhesion processes. All 84 differentially expressed proteins presented the same changing tendency in the SBP and SJP groups when compared with the Mod group. Among these 84 proteins, 25 proteins were found to be related to CVD. Among these 25 proteins, ACTB, ACTG1, FGA, FGB, FGG, PF4 and VWF were found to be involved in platelet aggregation and activation. FN1, HSPA5 and YWHAZ were associated with adhesion. CONCLUSIONS: The results of our study suggest that the cardioprotective effects of SBP and SJP are achieved through the modulation of focal adhesion, platelet activation pathways.

Dietary alpha-linolenic acid reduces platelet activation and collagen-mediated cell adhesion in sickle cell disease mice.

BACKGROUND: Sickle cell disease (SCD) is a genetic hemoglobinopathy associated with high morbidity and mortality. The primary cause of hospitalization in SCD is vaso-occlusive crisis (VOC), mediated by alteration of red blood cells, platelets, immune cells and a pro-adhesive endothelium. OBJECTIVES: We investigated the potential therapeutic use of the plant-derived omega-3 alpha-linolenic acid (ALA) in SCD. METHODS: Berkeley mice were fed a low- or high-ALA diet for 4 weeks, followed by analysis of liver fibrosis, endothelial activation, platelet activation and formation of platelet-neutrophils aggregates. Aggregation of platelets over collagen under flow after high-ALA was compared to a blocking P-selectin Fab. RESULTS: Dietary high-ALA was able to reduce the number of sickle cells in blood smear, liver fibrosis, and the expression of adhesion molecules on the endothelium of aorta, lungs, liver and kidneys (VCAM-1, ICAM-1 and vWF). Specific parameters of platelet activation were blunted after high-ALA feeding, notably P-selectin exposure and the formation of neutrophil-platelet aggregates, along with a correspondingly reduced expression of PSGL-1 on neutrophils. By comparison, in vivo treatment of SCD mice with the anti-P-selectin Fab was able to similarly reduce the formation of neutrophil-platelet aggregates, but did not reduce GpIbα shedding nor the activation of the αIIb ß3 integrin in response to thrombin. Both ALA feeding and P-selectin blocking significantly reduced collagen-mediated cell adhesion under flow. CONCLUSIONS: Dietary ALA is able to reduce the pro-inflammatory and pro-thrombotic state occurring in the SCD mouse model and may represent a novel, inexpensive and readily available therapeutic strategy for SCD.

[Research progress of change of platelet in blood stasis syndrome and effect of traditional Chinese medicine].

The traditional Chinese medicine(TCM) syndrome of blood stasis refers to blood stagnation in meridians and viscera, with the main symptoms of pain, mass, bleeding, purple tongue, and unsmooth pulse. Cardiovascular and cerebrovascular diseases are among the major chronic diseases seriously harming the health of the Chinese. Among the coronary heart disease and stroke patients, most demonstrate the blood stasis syndrome. Platelet is considered to be one of the necessary factors in thrombosis, which closely relates to the TCM syndrome of blood stasis and the occurrence of cardiovascular and cerebrovascular diseases. The clinical and laboratory research on platelet activation and aggregation has been paid more and more attention. Its purpose is to treat and prevent blood stasis syndrome. In this study, the authors analyzed the research on the dysfunctions of platelets in blood stasis syndrome, biological basis of TCM blood stasis syndrome, and the effect of blood-activating stasis-resolving prescriptions on platelets, aiming at providing a reference for exploring the mechanism of platelet intervention in the treatment of TCM blood stasis syndrome and the pathways and targets of Chinese medicine in the prevention and treatment of the syndrome.

Dietary Antiplatelets: A New Perspective on the Health Benefits of the Water-Soluble Tomato Concentrate Fruitflow®.

Our understanding of platelet functionality has undergone a sea change in the last decade. No longer are platelets viewed simply as regulators of haemostasis; they are now acknowledged to be pivotal in coordinating the inflammatory and immune responses. This expanded role for platelets brings new opportunities for controlling a range of health conditions, targeting platelet activation and their interactions with other vascular cells. Antiplatelet drugs may be of wider utility than ever expected but often cause platelet suppression too strong to be used out of clinical settings. Dietary antiplatelets represent a nutritional approach that can be efficacious while safe for general use. In this review, we discuss potential new uses for dietary antiplatelets outside the field of cardiovascular health, with specific reference to the water-soluble tomato extract Fruitflow®. Its uses in different aspects of inflammation and immune function are discussed, highlighting exercise-induced inflammation, mediating the effects of air pollution, and controlling thrombotic aspects of the immune response. Potential future developments in women's health, erectile dysfunction, and the allergic response indicate how broad the utility of dietary antiplatelets can be.

In vitro antiplatelet activity of extract and its fractions of Paulownia Clone in Vitro 112 leaves.

BACKGROUND: Paulownia Clone in Vitro 112, also known as Oxytree is a hybrid of Paulownia elongata and Paulownia fortunei, developed under laboratory conditions. Its seeds are sterile, making it a noninvasive variety that can only be propagated in the laboratory. In China, species from the Paulownia genus (Paulowniaceae) are widely used in traditional medicine for the treatment of infectious diseases, such as gonorrhea and erysipelas. It has a broad spectrum of bioactivity, including neuroprotective, antioxidant, antibacterial, antiphlogistic, antiviral, and cytotoxic actions. However, the antiplatelet potential of Paulownia Clone in Vitro 112 has not yet been described. STUDY DESIGN: The aim of our study was thus to examine the effect of an extract and four fractions from leaves of Paulownia Clone in Vitro 112 on various parameters of platelet activation in an in vitro model. METHODS: Composition of the investigated extract and fractions was determined by UHPLC-UV-MS. The following parameters of platelet activation were investigated: nonenzymatic lipid peroxidation in resting platelets; enzymatic lipid peroxidation (AA metabolism) in platelets activated by thrombin; superoxide anion (O2-.) generation in the resting and activated platelets; platelet adhesion to collagen type I and fibrinogen; platelet aggregation stimulated by various physiological agonists, such as ADP, collagen, and thrombin. The effect of the extract and fractions on extracellular LDH activity, a marker of cell damage, was also determined. RESULTS: Verbascoside a phenylethnanoid glycoside, was the main secondary metabolite of the extract from leaves of oxytree (constituting approximately 45 % of all compounds). There were also iridoids, such as catalpol, aucubin, and 7-hydroxytomentoside, as well as flavonoids, such as luteolin and apigenin glycosides. Moreover, the extract had stronger antiplatelet properties than the fractions. For example, the extract at 10 µg/mL inhibited five parameters of platelet activation. CONCLUSIONS: Our results show that Paulownia Clone in Vitro 112 leaves are a new valuable source of compounds with antiplatelet potential.

Platelet hyperactivity in COVID-19: Can the tomato extract Fruitflow® be used as an antiplatelet regime?

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus is now considered a global public health threat. The primary focus has been on reducing the viral spread and treating respiratory symptoms; as time goes on, the impact of COVID-19 on neurological and haemostatic systems becomes more evident. The clinical data suggest that platelet hyperactivity plays a role in the pathology of COVID-19 from its onset and that platelets may serve critical functions during COVID-19 progression. Hyperactivation of blood platelets and the coagulation system are emerging as important drivers of inflammation and may be linked to the severity of the 'cytokine storm' induced in severe cases of COVID-19, in which disseminated intravascular coagulation, and platelet hyperactivity are associated with poor prognosis and increased risk of mortality. We propose that targeting platelet hyperactivity in the early stages of COVID-19 infection may reduce the immunothrombotic complications of COVID-19 and subdue the systemic inflammatory response. Lowering baseline platelet activity may be of particular importance for higher-risk groups. As an alternative to antiplatelet drugs, an inappropriate intervention in public health, we propose that the dietary antiplatelet agent Fruitflow®, derived from tomatoes, may be considered a suitable therapy. Fruitflow® contains antiplatelet and anti-inflammatory compounds that target the mechanisms of platelet activation specific to COVID-19 and can be considered a safe and natural antiplatelet regime.

Thrombin Generation and other hemostatic parameters in patients with atrial fibrillation in use of warfarin or rivaroxaban.

Patients with atrial fibrillation (AF) present hyperactivation of both platelets and coagulation leading to a hypercoagulable state which contributes to an increased risk of thromboembolism. Therefore, one of the main strategies for treatment of AF is prevention of these events through the use of oral anticoagulants (OAC). The aim of this study was to evaluate hemostasis as a whole in patients with non-valvular AF undergoing warfarin or rivaroxaban by thrombin generation test (TGT), in addition to monocyte-platelet aggregates (MPA), glycoprotein IIb/IIIa (GPIIb/IIIa), and platelet (PMP) and endothelium (EMP) microparticles, compared to age and sex matched controls. PT/INR for OAC use was also determined. In patients taking OAC, compared to control group, a decrease in TGT (p = 0.000 for all parameters) were observed. Patients taking warfarin showed to be more hypocoagulable, presenting lower levels of ETP (p = 0.000) and peak (p = 0.002) than patients using rivaroxaban. Patients on warfarin use with INR > 3 had also lower levels of ETP (p = 0.01) and peak (p = 0.006). A decrease in ETP (p = 0.03) and peak (p = 0.02) values was also observed in patients using rivaroxaban with PT > 21.4 s. Patients using warfarin (p = 0.000) and rivaroxaban (p = 0.000) presented lower levels of MPA in relation to control group. It was also observed in patients using warfarin, lower GPIIb/IIIa levels in relation to control group (p = 0.011). Patients taking rivaroxaban (p = 0.003) and warfarin (p = 0.001) had higher PMP levels compared to control group. There was no difference in levels of EMP between the groups (p = 0.0536). The present study reinforces the usefulness of OAC in AF, which decisively contribute to a better management of the disease preventing possible complications.