This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.
Rats ; Animals ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/therapeutic use* ; Myocardial Infarction/genetics* ; Myocardium/metabolism* ; Aspirin/therapeutic use* ; TOR Serine-Threonine Kinases/metabolism* ; Membrane Proteins/metabolism* ; Mitochondrial Proteins

OBJECTIVES: Steroidal anti-inflammatory drugs have certain side effects in the treatment of hypertrophic scar, and the scar recurrence is easy after withdrawal of steroid anti-inflammatory drugs. Finding reliable alternative drugs is an effective means to improve this defect. Aspirin, a traditional non-steroidal anti-inflammatory drug, is safe for topical use and has anti-inflammatory effects similar to those of steroidal anti-inflammatory drugs, which may have similar effects on the treatment of hypertrophic scar. This study aims to investigate the inhibitory effect of aspirin on the proliferation of hypertrophic scar in rabbit ears and the underlying mechanism. METHODS: The rabbit ear hypertrophic scar models were prepared. The rabbits were randomly divided into a normal skin group (group A), a blank control group (group B), a 0.9% NaCl group (group C), a 0.2% aspirin group (group D), a 0.5% aspirin group (group E), a 2% aspirin group (group F), and a triamcinolone acetonide group (group G). Macroscopic observation of hyperplasia was performed 8 weeks after local injection of the scar, followed by collecting the scar tissue samples for HE staining, Masson staining, and immunohistochemistry, respectively to assess the proliferation of fibroblasts and collagen fibers, and calculate the hypertrophic index, microvessel density, and immunohistochemical score. RESULTS: All rabbit ear hypertrophic scar models were successfully constructed. In groups B and C, the hypertrophic scar edge was irregular, with reddish protruding epidermis, significant contracture and hard touch. In group D, E, and F, with the increase of aspirin administration concentration, the scar became thinner and gradually flat, the proliferation of fibrocytes and collagen fibers was weakened, and the hypertrophic index was gradually decreased (P<0.05). Immunohistochemistry showed that the expression of β-catenin was decreased in the group D, E and F in turn, and the immunohistochemical score was gradually decreased (P<0.05). There was no significant difference in hypertrophic index, microvessel density, and immunohistochemical score (all P>0.05). CONCLUSIONS Local injection of aspirin can reduce the generation of hypertrophic scar in a dose-dependent manner within a certain concentration range; aspirin inhibits the growth of hypertrophic scar in rabbit ears by inhibiting Wnt/β-catenin signal pathway; 2% aspirin and 40 mg/mL triamcinolone acetonide have similar curative efficacy on hypertrophic scar.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; Aspirin/therapeutic use* ; Cicatrix, Hypertrophic/pathology* ; Collagen ; Rabbits ; Signal Transduction ; Triamcinolone Acetonide/therapeutic use* ; beta Catenin/metabolism*

To explore the anti-platelet aggregation and anti-thrombotic mechanisms of Trichosanthis Fructus combined with aspirin based on network pharmacology and the validation of arteriovenous by pass model in rats. The databases of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome(DRAR-CPI),Universal Protein Resource(Uniprot) and the Database for Annotation,Visualization,and Integrated Discovery(DAVID) were used to predict protein targets and analyze biological pathway and signal pathway in the combination of Trichosanthis Fructus with aspirin. The effects of pretreatment with Trichosanthis Fructus pellets,aspirin pellets and their combination on thromboxane B2(TXB2),6-keto prostaglandin F1α(6-keto-PGF1α) and cyclic adenosine monophosphate(c AMP) in rat thrombotic model were studied. Through the study of network pharmacology,12 components of aspirin and Trichosanthis Fructus,including hydroxygenkwanin,quercetin and adenosine,were found to show the anti-platelet aggregation and anti-thrombosis mechanisms through9 common protein targets,such as SRC,RAC1,MAPK14,MAPK1,AKT1,and 14 common signaling pathways,such as VEGF signaling pathway. After the intervention with Trichosanthis Fructus pellets combined with aspirin pellets,the vascular endothslia growth factor(VEGF) signaling pathway can be activated to inhibit platelet aggregation and improve vascular endothelial function,and show the anti-platelet aggregation and anti-thrombosis mechanisms,which verify the results of the network pharmacology,and explain the anti-platelet aggregation and anti-thrombotic mechanisms of the combination of Trichosanthis Fructus pellets with aspirin pellets.
6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Aspirin ; pharmacology ; Cyclic AMP ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Fruit ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; Rats ; Signal Transduction ; Thrombosis ; drug therapy ; Thromboxane B2 ; metabolism ; Trichosanthes ; chemistry

Nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity reactions (HSRs) are often nonimmunologically mediated reactions which present with immediate HSR type manifestations. These are mediated by cyclooxygenase inhibition resulting in shunting towards the excessive production of leukotrienes. Important disease associations include asthma, nasal polyposis, and chronic spontaneous urticaria, especially among adults. The European Network on Drug Allergy/Global Allergy and Asthma European Network 2013 classification of NSAID HSR comprises nonselective HSR i.e., NSAID exacerbated respiratory disease (NERD), NSAIDs exacerbated cutaneous disease (NECD), NSAIDs induced urticarial-angioedema (NIUA); and selective (allergic) HSR i.e., single NSAID induced urticaria/angioedema or anaphylaxis, NSAIDs-induced delayed HSR. Much of the literature on genetic associations with NSAID HSR originate from Korea and Japan; where genetic polymorphisms have been described in genes involved in arachidonic acid metabolism, basophil/mast cell/eosinophil activation, various inflammatory mediators/cytokines, and different HLA genotypes. The Asian phenotype for NSAID HSR appears to be predominantly NIUA with overlapping features in some adults and children. NECD also appears to be more common than NERD, although both are not common in the Asian paediatric population. Between adults and children, children seem to be more atopic, although over time when these children grow up, it is likely that the prevalence of atopic adults with NSAID HSR will increase. Low-dose aspirin desensitization has been shown to be effective in the treatment of coronary artery disease, especially following percutaneous coronary intervention.
Adult ; Anaphylaxis ; Anti-Inflammatory Agents, Non-Steroidal ; Arachidonic Acid ; Asian Continental Ancestry Group ; Aspirin ; Asthma ; Child ; Classification ; Coronary Artery Disease ; Drug Hypersensitivity ; Genotype ; Humans ; Hypersensitivity ; Japan ; Korea ; Leukotrienes ; Metabolism ; Percutaneous Coronary Intervention ; Phenotype ; Polymorphism, Genetic ; Prevalence ; Prostaglandin-Endoperoxide Synthases ; Urticaria

OBJECTIVEVigna subterranea is widely consumed as a traditional staple food in Nigeria and some West African countries. The ethanolic seed extract of V. subterranea (EEVS) was investigated for its gastroprotective effects on aspirin plus pylorus ligation-induced gastric ulcerated rats using an in vivo assay.

METHODSGastric mucosal ulceration was induced experimentally in Groups 2 to 5 using aspirin plus pylorus ligation. Rats in Group 1 were orally pretreated with 3% Tween 80 only as normal control. Groups 2 to 5 were pretreated with 3% Tween 80 (ulcer group), 20 mg/kg of omeprazole (positive group), and 200 and 400 mg/kg of EEVS (experimental groups), respectively, once daily for 21 days before ulcer induction. Parameters including those for gastric secretions, ulcerated areas and gastric wall histology were assessed. Levels of superoxide dismutase (SOD), glutathione peroxidase (GP), and malondialdehyde (MDA) in the gastric tissue homogenate were also determined.

RESULTSPretreatment with EEVS significantly (P < 0.05) reduced the ulcer index, gastric volume and total acidity in rats with aspirin plus pylorus ligation-induced ulcer. The pH and mucus of gastric content increased significantly (P < 0.05) while the levels of SOD and GP were observed to be elevated with a reduced amount of MDA. Significant severe gastric mucosal injury was exhibited in the ulcer group and EEVS or omeprazole offered significant (P < 0.05) protection against mucosal ulceration. Histologically, the gastric submucosal layer showed remarkable decrease in edema and leucocytes infiltration compared with ulcer group.

CONCLUSIONThe study suggests that EEVS offered a protective action against aspirin plus pylorus ligation-induced gastric ulcers in Wistar rats. The protective effect might be mediated via antisecretory, cytoprotective and antioxidative mechanisms.

Animals ; Anti-Ulcer Agents ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Aspirin ; Edema ; Gastric Mucosa ; drug effects ; metabolism ; pathology ; Gastrointestinal Agents ; pharmacology ; therapeutic use ; Glutathione Peroxidase ; metabolism ; Hydrogen-Ion Concentration ; Leukocytes ; Male ; Malondialdehyde ; metabolism ; Mucus ; metabolism ; Nuts ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Severity of Illness Index ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism ; prevention & control ; Superoxide Dismutase ; metabolism ; Vigna

We have previously reported that NS-398, a cyclooxygenase-2 (COX-2)–selective inhibitor, inhibited replicative cellular senescence in human dermal fibroblasts and skin aging in hairless mice. In contrast, celecoxib, another COX-2–selective inhibitor, and aspirin, a non-selective COX inhibitor, accelerated the senescence and aging. To figure out causal factors for the senescence-modulating effect of the inhibitors, we here performed cDNA microarray experiment and subsequent Gene Set Enrichment Analysis. The data showed that several senescence-related gene sets were regulated by the inhibitor treatment. NS-398 up-regulated gene sets involved in the tumor necrosis factor β receptor pathway and the fructose and mannose metabolism, whereas it down-regulated a gene set involved in protein secretion. Celecoxib up-regulated gene sets involved in G2M checkpoint and E2F targets. Aspirin up-regulated the gene set involved in protein secretion, and down-regulated gene sets involved in RNA transcription. These results suggest that COX inhibitors modulate cellular senescence by different mechanisms and will provide useful information to understand senescence-modulating mechanisms of COX inhibitors.
Aging ; Animals ; Aspirin ; Celecoxib ; Cell Aging ; Cyclooxygenase 2 ; Fibroblasts* ; Fructose ; Gene Expression* ; Genes, vif ; Humans* ; Mannose ; Metabolism ; Mice ; Mice, Hairless ; Oligonucleotide Array Sequence Analysis ; RNA ; Skin Aging ; Tumor Necrosis Factor-alpha

Many reports have been published that provide epidemiological evidence supporting the efficacy of aspirin and non-steroidal anti- inflammatory drugs (NSAIDs) in cancer prevention. The presumed mechanism of chemoprevention is inhibition of cyclooxygenase (COX)-2. Aspirin exhibits an anticancerous effect through several inter-related mechanisms: prostaglandin synthesis and catabolism in epithelial cells, inhibition of Wnt-β-catenin signaling, inactivation of platelets, and the host immune response. Several clinical studies have demonstrated that aspirin and NSAIDs exhibit chemopreventive effects in stomach cancer. However, well-designed clinical studies to answer critical clinical questions such as additional benefits of aspirin or NSAIDs after eradication of Helicobacter pylori, and the net benefit despite the adverse effects of long-term intake of aspirin or NSAIDs, are needed.
Anti-Inflammatory Agents, Non-Steroidal ; Aspirin* ; Chemoprevention* ; Epithelial Cells ; Helicobacter pylori ; Metabolism ; Prostaglandin-Endoperoxide Synthases ; Stomach Neoplasms*

BACKGROUNDPlatelet function tests are widely used in clinical practice to guide personalized antiplatelet therapy. In China, the thromboelastography (TEG) test has been well accepted in clinics, whereas VerifyNow, mainly used for scientific research, has not been used in routine clinical practice. The aim of the current study was to compare these two point-of-care platelet function tests and to analyze the consistency between the two tests for evaluating on-clopidogrel platelet reactivity in Chinese acute myocardial infarction patients undergoing percutaneous coronary intervention (PCI).

METHODSA total of 184 patients admitted to Fuwai Hospital between August 2014 and May 2015 were enrolled in the study. On-clopidogrel platelet reactivity was assessed 3 days after PCI by TEG and VerifyNow using adenosine diphosphate as an agonist. Based on the previous reports, an inhibition of platelet aggregation (IPA) <30% for TEG or a P2Y12 reaction unit (PRU) >230 for VerifyNow was defined as high on-clopidogrel platelet reactivity (HPR). An IPA >70% or a PRU <178 was defined as low on-clopidogrel platelet reactivity (LPR). Correlation and agreement between the two methods were analyzed using the Spearman correlation coefficient (r) and kappa value (κ), respectively.

RESULTSOur results showed that VerifyNow and TEG had a moderate but significant correlation in evaluating platelet reactivity (r = -0.511). A significant although poor agreement (κ = 0.225) in identifying HPR and a significantly moderate agreement in identifying LPR (κ = 0.412) were observed between TEG and VerifyNow. By using TEG as the reference for comparison, the cutoff values of VerifyNow for the Chinese patients in this study were identified as PRU >205 for HPR and PRU <169 for LPR.

CONCLUSIONSBy comparing VerifyNow to TEG which has been widely used in clinics, VerifyNow could be an attractive alternative to TEG for monitoring on-clopidogrel platelet reactivity in Chinese patients.

Adenosine Diphosphate ; therapeutic use ; Aged ; Aspirin ; therapeutic use ; Blood Platelets ; drug effects ; China ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; surgery ; Percutaneous Coronary Intervention ; methods ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; therapeutic use ; Point-of-Care Systems ; Receptors, Purinergic P2Y12 ; metabolism ; Thrombelastography ; Ticlopidine ; analogs & derivatives ; therapeutic use

OBJECTIVETo determine the effect of aspirin on cell proliferation, alkaline phosphatase (ALP) activity, cell cycle and apoptosis in murine bone marrow stromal cells, so as to explore an appropriate dose range to improve bone regeneration in periodontal treatment.

METHODSST2 cells were stimulated with aspirin (concentrations of 1, 10, 100 and 1 000 μmol/L) for 1, 2, 3, 5 and 7 d. Cell proliferation was measured by methyl thiazolyl tetrazolium (MTT) assay. After ST2 cells were treated for 1, 3 and 7 d, ALP activity was measured by ALP kit, cell cycle and apoptosis were measured by flow cytometry (FCM) after treated for 48 h.

RESULTSMTT assays showed that various doses of aspirin have different effects on the cell growth. Briefly, lower concentrations (1, 10 μmol/L) of aspirin promoted the cell growth, the A value of 0, 1 and 10 μmol/L aspirin 7-day-treated cells were 0.313±0.012, 0.413±0.010 and 0.387±0.017 respectively (P <0.01 vs control), and so did the ALP level ([4.3±0.9], [6.0±0.3] and [7.7±0.4] μmol·min(-1)·g(-1), P <0.05 vs control), while higher concentrations, especially 1000 μmol/L of aspirin might inhibit the cell growth with time going, A value and ALP level were 0.267±0.016, (4.3±1.3) μmol·min(-1)·g(-1) respectively (P <0.05 vs control). Cell cycle analysis revealed no changes in comparison to control cells after treatment with 1 or 10 μmol/L aspirin, but it was observed that cell mitosis from S phase to G2/M phase proceeded at higher concentrations of 100 μmol/L aspirin, and the cell cycle in phase G0/G1 arrested at 1000 μmol/L. Parallel apoptosis/necrosis studies showed that the percentage of cells in apoptosis decreased dramatically at all doses of aspirin, the apoptosis rates of ST2 cells responded to 0, 1, 10, 100 and 1000 μmol/L aspirin were (11.50±0.90)%, (5.30±0.10)%, (5.50±0.10)%, (4.90±0.90)% and (7.95±0.25)% respectively (P<0.05 vs control).

CONCLUSIONSThis study demonstrated that lower dosage of aspirin can promote ST2 cells growth, osteogenic activity and inhibit its apoptosis. Aspirin maybe used for the bone reconstruction with a proper concentration.

Alkaline Phosphatase ; metabolism ; Animals ; Apoptosis ; drug effects ; Aspirin ; administration & dosage ; pharmacology ; Bone Regeneration ; Cell Cycle ; drug effects ; Cell Division ; Cell Line, Tumor ; Cell Proliferation ; Flow Cytometry ; Formazans ; Mesenchymal Stromal Cells ; cytology ; drug effects ; enzymology ; Mice ; Periodontics ; Tetrazolium Salts ; Time Factors

OBJECTIVETo provide a theoretical basis for the further development of new drugs, the analgesic and anti-inflammatory effects and the liver function in mice of anthocyanin from Ligustrum vicaryi were investigated.

METHODSThe 240 experimental mice were splitted equally for 6 kinds of experiments and 40 rats in each kind of experiment were divided into 5 groups (n = 8): normal saline control group (NS); aspirin control group (Asp); high-concentration anthocyanin group (HA); medium-concentration anthocyanin group (MA); low-concentratior anthocyanin group (LA). The analgesia effect of anthocyanin at different concentration was detenmined by hot-plate test and acetic acid writhin test, and the anti-inflammatory effect of anthocyanin was performed by ear edema, ahdomen capillary permeability and cotton granuloma. The activities of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) and the contents of nitric oxide (NO) and prostaglandin E2 (PGE2) in blood serum were determined, and the activities of SOD, T-AOC and glutathione peroxidase (GSH-Px) in liver were measured, while the histological changes of liver tissue were observed.

RESULTSThe pain threshold of mice was enhanced and the times of twist body wa decreased by medium-concentration and high-concentration anthocyanin. The activity of SOD was increased and the conentrs of NO and PGE were reduced in blood serum. High-concentration anthocyanin inhibited the ear swelling , the increase of celiac capillary permeability and th granuloma hyperplasia, and increased the activities of SOD and T-AOC while decreased the content of PGE2. The activities of SOD, T-AOC. GSH-PX were increased in liver, but the morphology of liver tissues in each group had no significant changes.

CONCLUSIONAnthocyanin Ligustrum vicaryi has definite anti-inflammatory and analgesic effects, which is related to increasing the antioxidant capacity and decreasing th contents of NO and PGE2, and has not obvious damage to liver in the range of experimental concentration.

Analgesics ; chemistry ; Animals ; Anthocyanins ; pharmacology ; Anti-Inflammatory Agents ; chemistry ; Antioxidants ; metabolism ; Aspirin ; pharmacology ; Dinoprostone ; metabolism ; Edema ; Fruit ; chemistry ; Glutathione Peroxidase ; metabolism ; Ligustrum ; chemistry ; Liver ; drug effects ; Mice ; Nitric Oxide ; Superoxide Dismutase ; metabolism