Oral Administration Of Aspirin Research Articles

Zhilong Huoxue Tongyu Capsule Ameliorates Platelet Aggregation and Thrombus Induced by Aspirin in Rats by Regulating Lipid Metabolism and MicroRNA Pathway.

Zhilong Huoxue Tongyu capsule (ZLHX) is a traditional Chinese medicinal compound preparation, which exhibits obvious therapeutic effects on aspirin resistance (AR). However, the mechanism of ZLHX on AR is rarely reported. This study aimed to explore the therapeutic effects of AR and the underlying mechanisms of ZLHX on AR rats. An AR model was established through treatment with a high-fat, high-sugar, and highsalt diet for 12 weeks and oral administration of aspirin (27 mg/kg/day) and ibuprofen (36 mg/kg/day) in weeks 9-12. The rats were administrated with ZLHX (225, 450, and 900 mg/kg) from week 12 to week 16. Blood samples were collected after the experiment. Thromboelastography analysis was performed, and the levels of triglyceride (TG), total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined. Furthermore, the levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6- keto-PGF1α) were determined with commercial ELISA kits. Finally, the gene expressions of microRNA- 126-3p (miRNA-126-3p) and miRNA-34b-3p were detected through a real-time quantitative polymerase chain reaction. Results demonstrated that ZLHX significantly inhibited platelet aggregation in the AR rats. Moreover, ZLHX markedly decreased the levels of TC, TG, and LDL-C and increased the level of HDL-C. Meanwhile, ELISA results confirmed that ZLHX can elevate the expression levels of TXB2 and 6-keto-PGF1α. Further studies suggested that ZLHX significantly downregulated the expression levels of miRNA-126-3p and miRNA-34b-3p. This study revealed that the therapeutic effect of ZLHX might be related to the regulation of lipid metabolism and the miRNA pathway.

Aspirin inhibits rotavirus replication and alters rat gut microbial composition

BackgroundAspirin is widely used to treat various clinical symptoms. Evidence suggests that aspirin has antiviral properties, but little is known about its specific effect against rotavirus.MethodsMA104, Caco-2, and CV-1 cells were infected with rotavirus, and aspirin was added after 12 h. Viral mRNA and titer levels were measured by qRT-PCR and immunofluorescence assays. For in vivo validation, forty specific-pathogen-free SD rats were randomly divided into oral aspirin (ASP) groups and control (NC) groups. 16 S rRNA gene sequencing was performed to identify gut microbiota. After 6 months of continuous ASP/NC administration, the rats were infected with rotavirus. Fecal samples were collected over a 30-day time course, and viral levels were quantified. Proinflammatory cytokines/chemokine levels were measured by ELISA.ResultsAspirin inhibited rotavirus infection in cell lines and in rats. The effects of aspirin on viral replication were associated with the alteration of gut microbiota composition by aspirin, including increased abundance of Firmicutes and decreased abundance of Bacteroidetes after aspirin treatment. Mechanistically, aspirin reduced IL-2 and IL-10 levels, and increased IRF-1 and COX-2 levels. Aspirin blocked rotavirus replication in vitro and in vivo, which might be related to effects on IRF-1, COX-2, chemokines, and gut microbial composition.ConclusionThese results indicate that long-term oral aspirin administration reduces rotavirus infection. Intestinal virus infection may be suppressed in elderly patients who take aspirin for a long time. The change of their Gut microbiota may lead to functional disorder of the intestinal tract, which may provide some reference for clinical adjuvant probiotics treatment.

Treatment of inadvertent cervical arterial catheterization: Single-center experience.

Inadvertent arterial catheterization can occur during transjugular central venous catheter insertion and should be promptly treated to prevent serious consequences. Although many treatment modalities are available, no exist guidelines regarding the selection of treatment. We aimed to describe our experience with the treatment of 11 patients who underwent inadvertent cervical arterial catheterization and propose an algorithm for the selection of treatment methods. We retrospectively identified all patients who were treated for inadvertent arterial catheterization at our center between January 2016 and March 2021. We reviewed patient profiles, images, treatment methods, and follow-up data. Eleven patients were included (eight men and three women, age: 36-73years). Ten catheter misplacements were in the right common carotid artery. The remaining catheter was inserted into the right subclavian artery after penetrating the right common carotid artery. Two catheters were 5-Fr and nine catheters were 11.5-Fr. Two patients underwent manual compressions, three underwent open surgery, three underwent stent-graft repairs, and four underwent Perclose Proglide closure. Clinical success was achieved in all 11 patients. Primary technical success was achieved in 10 patients. In one patient, unsuccessful manual compression was followed by successful stent-graft repair; the manual compression failed to prevent bleeding, possibly because of the long-term oral administration of aspirin for coronary heart disease. The mean follow-up was 5.4months (range, 1-12months). The overall mortality rate was zero, and no vascular or neurological events occurred. The existing data show that the current protocol for the treatment of inadvertent cervical arterial catheterization at our center is safe and effective. However, the data are insufficient and require further clinical validation.

Deletion of platelet CLEC-2 decreases GPIbα-mediated integrin αIIbβ3 activation and decreases thrombosis in TTP

AbstractMicrovascular thrombosis in patients with thrombotic thrombocytopenic purpura (TTP) is initiated by GPIbα-mediated platelet binding to von Willebrand factor (VWF). Binding of VWF to GPIbα causes activation of the platelet surface integrin αIIbβ3. However, the mechanism of GPIbα-initiated activation of αIIbβ3 and its clinical importance for microvascular thrombosis remain elusive. Deletion of platelet C-type lectin-like receptor 2 (CLEC-2) did not prevent VWF binding to platelets but specifically inhibited platelet aggregation induced by VWF binding in mice. Deletion of platelet CLEC-2 also inhibited αIIbβ3 activation induced by the binding of VWF to GPIbα. Using a mouse model of TTP, which was created by infusion of anti-mouse ADAMTS13 monoclonal antibodies followed by infusion of VWF, we found that deletion of platelet CLEC-2 decreased pulmonary arterial thrombosis and the severity of thrombocytopenia. Importantly, prophylactic oral administration of aspirin, an inhibitor of platelet activation, and therapeutic treatment of the TTP mice with eptifibatide, an integrin αIIbβ3 antagonist, reduced pulmonary arterial thrombosis in the TTP mouse model. Our observations demonstrate that GPIbα-mediated activation of integrin αIIbβ3 plays an important role in the formation of thrombosis in TTP. These observations suggest that prevention of platelet activation with aspirin may reduce the risk for thrombosis in patients with TTP.

Aspirin Reduces Ischemia-Reperfusion Injury Induced Endothelial Cell Damage of Arterial Grafts in a Rodent Model.

Long-term graft patency determines the prognosis of revascularization after coronary artery bypass grafting (CABG). Ischemia-reperfusion (I/R) injury of the graft suffered during harvesting and after implantation might influence graft patency. Aspirin, a nonsteroidal anti-inflammatory drug improves the long-term patency of vein grafts. Whether aspirin has the same effect on arterial grafts is questionable. We aimed to characterize the beneficial effects of aspirin on arterial bypass grafts in a rodent revascularization model. We gave Lewis rats oral pretreatment of either aspirin (n = 8) or saline (n = 8) for 5 days, then aortic arches were explanted and stored in cold preservation solution. The third group (n = 8) was a non-ischemia-reperfusion control. Afterwards the aortic arches were implanted into the abdominal aorta of recipient rats followed by 2 h of reperfusion. Endothelium-dependent vasorelaxation was examined with organ bath experiments. Immunohistochemical staining were carried out. Endothelium-dependent maximal vasorelaxation improved, nitro-oxidative stress and cell apoptosis decreased, and significant endothelial protection was shown in the aspirin preconditioned group, compared to the transplanted control group. Significantly improved endothelial function and reduced I/R injury induced structural damage were observed in free arterial grafts after oral administration of aspirin. Aspirin preconditioning before elective CABG might be beneficial on free arterial graft patency.

Aspirin Inhibits Platelets from Reprogramming Breast Tumor Cells and Promoting Metastasis

Introduction: It is now recognized that tumor cells activate platelets, causing them to degranulate and release soluble factors that promote angiogenesis and metastasis. However, it is unknown if these released factors (‘platelet releasate‘) can also affect tumor cell signaling to further drive metastasis.Methods: We used in vitro arrays, ELISA, and invasion assays to study the interactions between platelets and tumor cells in culture. In addition we used an in vivo murine model of mice treated with aspirin and ex vivo patient data from breast cancer patients on aspirin therapy.Results: Breast tumor cells secrete up to 50-fold increased levels of interleukin 8 (IL-8, CXCL8) in response to platelet releasate in vitro, and this tumor-secreted IL-8 is necessary in driving platelet-mediated invasion. Upon characterizing the contents of the platelet releasate, we determined that chemokine (C-C motif) ligand 5 (CCL5) was the component of the platelet releasate that drove IL8 induction in tumor cell lines expressing the CCL5 receptor, CCR5. The mechanism of this platelet-mediated IL-8 induction was found to be activation of the AKT pathway in breast tumor cells; inhibition of this pathway eliminated IL-8 production.We therefore hypothesized that inhibiting platelet activation with aspirin could reverse the effects of platelets on pro-metastatic tumor cell signaling. Platelets treated ex vivo with 100 uM aspirin had up to 51% lower activation in response to tumor cells, released 40% less CCL5, did not activate the AKT pathway, resulted in lower levels of IL-8 production, and did not significantly increase breast tumor cell invasion. In a murine in vivo breast cancer model, immunohistochemistry of MCF-7ras tumor cells revealed that oral administration of aspirin resulted in less secretion of IL-8. In addition, samples were collected from breast cancer patients on aspirin therapy or not; patients on aspirin had 42% less circulating IL-8 and their platelets were less able to drive tumor cell invasion in vitro when compared to patients not on aspirin.Conclusions: Our data suggest that platelets drive breast tumor metastasis by releasing CCL5, activating AKT signaling, and stimulating tumor cells to upregulate and secrete IL-8. Furthermore, we propose aspirin acts as an anti-cancer agent by disrupting the communication between platelets and breast tumor cells. DisclosuresItaliano:Platelet BioGenesis: Equity Ownership; VCAN Bio: Membership on an entity's Board of Directors or advisory committees.

Protective effects of Dialium guineense pulp on aspirin-induced gastric mucosal injury in albino rats.

The numerous challenges and detrimental effects connected with the treatment of peptic ulcers in the world today calls for alternative attention. Ethnomedicinally, Dialium guineense pulp (DAGP) has numerous pharmacological activities. This study investigated the anti-ulcer activities of Dialium guineense pulp on gastric mucosa injury induced with aspirin in albino Wistar rats. DAGP extract was orally administered at doses of 250, 500 and 1000 mg/kg bw (mg per kg of the body weight) per day for 3 or 7 days followed by 400 mg/kg bw oral aspirin administration. Ulcer indices were determined, followed by a biochemical estimation of antioxidant enzymes using gastric mucosal tissue from the stomach. Student's t-test was used to compare significant differences among groups of animals at P ≤ 0.05. The results showed that Dialium guineense pulp caused a significant decrease (P ≤ 0.05) in the ulcer index in aspirin induced rats. This decrease in ulcer index is dose dependent and 1000 mg/kg bw per day caused the highest decrease in 7 days. The results showed a significant increase (P ≤ 0.05) in lipid peroxidation and a decrease (P ≤ 0.05) in antioxidant enzymes activities in the aspirin-induced ulcerated rats. Oral administration of DAGP increased antioxidant enzymes activities and decreased injury in the gastric mucosa in ulcer induced rats. Therefore, this study showed that DAGP exhibited anti-ulcer potential and that the gastrointestinal protection may be through the scavenging action of free radicals by its constituent antioxidants. Thus, Dialium guineense pulp has ameliorative medicinal potential for the curing of gastric disorders.

Dextranum in Combination with Low-Molecular-Weight Heparin Prevents the Portal Vein Thrombosis after Splenectomy for Portal Hypertension

This study aimed to explore the effect of dextranum in combination with low-molecular-weight heparin on the prevention of portal vein thrombosis after splenectomy for portal hypertension. Between February 2015 and February 2019, we enrolled 128 liver cirrhosis patients with portal hypertension as the subjects which were later divided randomly into the observation group and the control group, with 64 patients in each group. All patients received the splenectomy in combination with the esophagogastric devascularization. Following the surgery, dextranum was given to the patients in two groups for prevention of portal vein thrombosis, while those in the observation would additionally took low-molecular-weight heparin for prophylaxis of portal vein thrombosis. After medication, incidence of portal vein thrombosis after surgery was recorded, and at 1 d and 14 d after surgery, the platelet count in peripheral blood was also detected; furthermore, we recorded the condition of patients in preventive anti-coagulation treatment, oral administration of enteric-coated aspirin, postoperative hospitalization days and the incidence of complications, including gastrointestinal bleeding and liver failure, within 3 mo after operation. In the observation group, the incidence rate of postoperative portal vein thrombosis was 9.37 %, significantly lower than 31.25 % in the control group (p<0.05), while the difference in the platelet count test at 1 d after operation showed no statistical significance (p>0.05), and the platelet count test showed an increasing trend at 14 d after operation (p<0.05); however, the intergroup comparison showed no significant difference (p>0.05). Between two groups, the duration of preventive anti-coagulation treatment and oral administration of aspirin showed no significant difference (p>0.05), while the patients had a shorter hospitalization duration in the observation group than their counterparts in the control group (p<0.05). Within 3 mo after operation, the incidence rate of complications, including gastrointestinal bleeding and liver failure, in the observation group was 6.25 %, significantly lower than 26.56 % in the control group (p<0.05). After splenectomy for portal hypertension, dextranum in combination with the low-molecularweight heparin can prevent the portal vein thrombosis by inhibiting the platelet aggregation, thereby promoting the patients’ recovery and decreasing the incidence of postoperative complications.

Initial Report of the Perioperative Platelet Aggregation Test Using Hematracer ZEN in Neuroendovascular Therapy.

We report the characteristics of the platelet aggregation test using Hematracer ZEN (HTZ; DS medical, Tokyo, Japan) during the perioperative period. Among patients undergoing neuroendovascular treatment (EVT) at our hospital between June 2019 and June 2020, 42 consecutive patients with preoperative dual antiplatelet therapy (DAPT) were included. Oral administration of aspirin (ASA) at 81 mg and clopidogrel (CLP) at 75 mg was started 7 days before treatment (Flow Diverter [FD]: 14 days before). We evaluated platelet aggregation activity the day before treatment (FD: 2 days before) using HTZ. We adjusted the CLP dose according to the platelet aggregation test in each patient. We evaluated the platelet aggregating activity after EVT in patients requiring an intracranial stent or in which CLP was adjusted before EVT. Platelet aggregating activity was able to be evaluated in all patients. In the preoperative examination, the efficacy of CLP was insufficient in one patient (2.4%), optimal medical effects were confirmed in 16 (38.1%), mildly excessive effects were noted in 10 (23.8%), and highly excessive effects were noted in 15 (35.7%). Reassessment was performed postoperatively in 20 patients. We switched CLP to prasugrel in one patient in which the CLP efficacy was considered insufficient in the preoperative evaluation. We reduced the CLP dose in seven patients with marked overdose, and the optimum range was reached in all. We did not adjust the CLP dose in 12 patients judged to have optimal or mildly excessive effects preoperatively, but 4 exhibited highly excessive drug efficacy and required CLP reduction. No postoperative symptomatic cerebral infarction or intracranial hemorrhage was observed (mean observation period: 11 months, range: 4-16 months). The platelet aggregation test using HTZ was simple and inexpensive, and was useful for adjusting the dose of antiplatelet drugs, but its utility should be evaluated in more patients.

Adjunctive treatment with low dose intra-arterial eptifibatide and intravenous aspirin during carotid stenting: A case series

PurposeAccording to most guidelines, medical protocol for carotid stenting includes the administration of oral Aspirin and Clopidogrel at least four days before the procedure, with intraprocedural intravenous (IV) heparin. Some publications have also reported the safety of adding glycoprotein 2b/3a inhibitors to the protocol. In this retrospective study, we evaluate the safety of a new medication protocol that includes IV aspirin and intra-arterial Eptifibatide (glycoprotein 2b/3a inhibitor) during carotid stenting. All patients who underwent carotid stenting at Soroka University Medical Center between January 2015 and May 2020 were included (emergent cases were excluded). We divided patients into two groups—patients treated under the standard protocol, and patients treated under the new protocol. In the latter, patients received both the standard protocol regimen, as well as 150 mg IV aspirin immediately before stenting, and a slow intra-arterial injection of 2–3 mg Eptifibatide (glycoprotein 2b/3a antagonist) immediately after stenting. Forty-four patients were treated according to the standard protocol (group 1), and 41 patients were treated according to the new protocol (group 2). In group 1, six patients had complications, while in group 2, no complications of any kind were noted (p = 0.027). The safety and possible efficacy of this novel protocol was preliminarily demonstrated in the present study. Future studies are needed to prove the safety and efficacy of a specific drug regimen that will further reduce the complication rates of carotid stenting.

Comparison of thrombocyte counts during the post-oral administration of aspirin and the Holothuria scabra ethanol extract in Wistar rats (Rattus norvegicus)

Background: Long bleeding time is a risk factor in dental treatment, especially in patients who consume aspirin or other antithrombotic drugs. Holothuria scabra (H. scabra) are mostly echinodermata and have been studied in Indonesia; they contain omega-3 and glycosaminoglycans, with an influence of an antithrombotic drug. Purpose: This study aimed to investigate the thrombocyte counts during the post-administration of aspirin and the H. scabra extract in Wistar rats (Rattus norvegicus). Methods: This study was true experimental with a post-test control group design. The sample consisting of 30 healthy male Wistar rats (R. norvegicus) with a bodyweight of 150–250 g was divided into three groups (n = 10). The rats in Group 1 were given sodium carboxymethyl cellulose (Na CMC). The rats in Group 2 were given aspirin, and the rats in Group 3 were given the H. scabra ethanol extract with a 25 mg/200 g dose as per their body weight (BW). Oral administration was given for seven days. The rats’ blood was taken on the eighth day. The amount of thrombocyte was measured using Wright’s stain methods. The analysis of variance (ANOVA) and the Least Significant Difference (LSD) tests were conducted for data analysis (p &lt; 0.05). Results: The thrombocyte counts (179.00 ± 10.56) in aspirin administration were lower than those in H. scabra (265.00 ± 18.54) and control groups (334.17 ± 13.9), with a significant difference between the groups (p = 0.0001; p &lt; 0.05). Conclusion: This study indicates that the oral administration of aspirin and H. scabra decreases thrombocyte counts, whereas the administration of aspirin reduces thrombocyte counts to levels lower than those in H. scabra in Wistar rats (R. norvegicus).

P4158Marked impairment of endothelium-dependent digital vasodilatations in patients with microvascular angina compared with those with vasospastic angina

Abstract Background/Introduction Nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) factor are the major endothelium-derived relaxing factors. NO plays an important role in conduit arteries, while the importance of EDH factor increases as the vessel size decrease in patients with microvascular angina (MVA) compared with those with vasospastic angina (VSA) remains to be fully elucidated. Purpose We evaluated the roles of NO and EDH factor in conduit (brachial) arteries and resistance (digital) arteries of the patients with MVA, VSA and comorbid MVA+VSA patients. Methods We enrolled 39 patients who underwent diagnostic cardiac catheterization and divided them into 3 groups based on acetylcholine (ACh) provocation test, index of microcirculation resistance (IMR), and coronary flow reserve (CFR); MVA (N=9, mean age 59.9±3.5 years), VSA (N=12, mean age 61.3±1.8 years), and comorbid MVA+VSA (N=18, mean age 64.0±2.2 years). Endothelium-dependent brachial and digital vasodilatations in response to intra-arterial infusion of bradykinin (BK, 25, 50, and 100 ng/min for 2 min) were simultaneously measured by ultrasonography and peripheral arterial tonometry, respectively. Measurements were repeated after oral administration of aspirin (486 mg) and intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA, 8μmol/min for 5 min) in order to inhibit the effects of vasodilator prostaglandins and NO, respectively. Finally, endothelium-independent brachial and digital vasodilatations in response to sublingual nitroglycerin (NTG, 0.3 mg) were measured in the same manner. Results In the brachial artery, dose-dependent vasodilatations to BK were comparable among the 3 groups, and L-NMMA equally attenuated the responses to BK (Figure 1). Endothelium-independent brachial vasodilatation in response to NTG was also comparable among the 3 groups. Surprisingly, dose-dependent digital vasodilatations to BK were almost absent in MVA patients compared with VSA or comorbid MVA+VSA group (Figure 2). Furthermore, the digital vasodilatations were unaffected by L-NMMA in VSA group, but were significantly reduced in comorbid MVA+VSA group (VSA, 16.8±15.1% vs. MVA+VSA, −0.23±6.2%, P&lt;0.05), suggesting reduced EDH and compensatory role of NO in the latter group. In contrast, endothelium-independent digital vasodilatation in response to NTG was comparable among the 3 groups. The main results of this study Conclusions These results provide the first evidence that endothelium-dependent digital vasodilatations (both NO and EDH factor) are markedly impaired in MVA patients compared with VSA or comorbid MVA+VSA patients, whereas the responses are comparable in the brachial artery among the 3 groups, suggesting the involvement of severe endothelial dysfunction in the pathogenesis of MVA.

Spirulina ameliorates aspirin-induced gastric ulcer in albino mice by alleviating oxidative stress and inflammation

Aspirin is a commonly prescribed non steroidal anti-inflammatory drug, but its prolonged use injures the gastric mucosa. The present study was carried out to evaluate the ameliorative effect of spirulina against aspirin-induced gastric ulcer in albino mice. Gastric ulcer was induced by oral administration of aspirin (500 mg/kg bw). Spirulina (250 and 500 mg/kg bw) was given orally for 3 days after the induction of gastric ulcer. Spirulina ameliorated aspirin-induced gastric ulcer by improving the gross morphology, histology and mucous layer of gastric tissue, augmenting the endogenous enzymatic and non-enzymatic antioxidants (reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase) and the cytoprotective marker (COX-1), and by alleviating tissue levels of the lipid peroxidation marker (malondialdehyde) and inflammatory mediators (TNF-α, COX-2 and NO). In conclusion, spirulina has a therapeutic potential in aspirin-induced gastric injury by alleviating oxidative stress and inflammation.

Low-dose daily aspirin reduces topical minoxidil efficacy in androgenetic alopecia patients.

Topical minoxidil is the only US FDA approved OTC drug for the treatment of androgenetic alopecia (AGA). Minoxidil is a pro-drug converted into its active form, minoxidil sulfate, by the sulfotransferase enzymes in the outer root sheath of hair follicles. Previously, we demonstrated that sulfotransferase activity in hair follicles predicts response to topical minoxidil in the treatment of AGA. In the human liver, sulfotransferase activity is significantly inhibited by salicylic acid. Low-dose OTC aspirin (75-81 mg), a derivative of salicylic acid, is used by millions of people daily for the prevention of coronary heart disease and cancer. It is not known whether oral aspirin inhibits sulfotransferase activity in hair follicles, potentially affecting minoxidil response in AGA patients. In the present study, we determined the follicular sulfotransferase enzymatic activity following 14 days of oral aspirin administration. In our cohort of 24 subjects, 50% were initially predicted to be responders to minoxidil. However, following 14 days of aspirin administration, only 27% of the subjects were predicted to respond to topical minoxidil. To the best of our knowledge, this is the first study to report the effect of low-dose daily aspirin use on the efficacy of topical minoxidil.

Glabella impending skin necrosis: a case report

A 47-year-old female patient undergoing hyaluronic acid injection in the glabella region suffered intravascular injection leading to marked discoloration (whitening) of the whole angiosome of the supratrochlear artery, extending to the areas of the anastomoses to the left upper eyelid, the dorsum of the nose, and the left sidewall of the nose. The syringe was immediately withdrawn while aspirating and prompt salvage counter-measures were taken, including application of warm compresses, vigorous massaging, oral administration of aspirin, repeated injections of hyaluronidase, and application of nitroglycerine paste on the affected area. The patient was followed up on a daily basis and the only additional treatment was the application of a combined antibiotic/steroid cream. The area affected healed satisfactorily with no scarring after 20 days. Our treatment protocol is discussed with special mention to the emerging role of hyaluronidase as the single most important rescue measure in the treatment of hyaluronic acid filler-related vascular adverse events. Level of Evidence: Level V, therapeutic study

Low-Dose Aspirin Upregulates Tyrosine Hydroxylase and Increases Dopamine Production in Dopaminergic Neurons: Implications for Parkinson's Disease.

Increasing the function of residual dopaminergic neurons in the nigra of PD patients is an important area of research as it may eventually compensate the loss. Although tyrosine hydroxylase (TH) is the rate-limiting enzyme in the dopamine (DA) biosynthesis pathway, there are no effective drugs/molecules to upregulate TH and increase the production of DA in nigral dopaminergic neurons. This study underlines the importance of aspirin in stimulating the expression of TH and increasing the level of DA in dopaminergic neurons. At low doses, aspirin increased the expression of TH and the production of DA in mouse MN9D dopaminergic neuronal cells. Accordingly, oral administration of aspirin increased the expression of TH in the nigra and upregulated the level of DA in striatum of normal C57/BL6 mice and aged A53T α-syn transgenic mice. Oral aspirin also improved locomotor activities of normal mice and A53T transgenic mice. While investigating mechanisms, we found the presence of cAMP response element (CRE) in the promoter of TH gene and the rapid induction of cAMP response element binding (CREB) activation by aspirin in dopaminergic neuronal cells. Aspirin treatment also increased the level of phospho-CREB in the nigra of C57/BL6 mice. The abrogation of aspirin-induced expression of TH by siRNA knockdown of CREB and the recruitment of CREB to the TH gene promoter by aspirin suggest that aspirin stimulates the transcription of TH in dopaminergic neurons via CREB. These results highlight a new property of aspirin in stimulating the TH-DA pathway, which may be beneficial in PD patients. Graphical Abstract ᅟ.

Protective Effects of Methanol Extract ofVernonia amygdalina(del.) Leaf on Aspirin-Induced Gastric Ulceration and Oxidative Mucosal Damage in a Rat Model of Gastric Injury

This study investigated the quantitative polyphenolic constituents and gastroprotective effects of methanol extract of Vernonia amygdalina leaf (MEVA) against aspirin-induced gastric ulcer in rats. Ulceration was induced by 3 days’ oral administration of aspirin (150 mg/kg body weight). Wistar rats were pretreated with cimetidine (reference drug) at a dose of 100 mg/kg body weight and MEVA at 200, 300, and 400 mg/kg body weight once daily for 28 days prior to ulcer induction. At the end of the experiment, gastric secretions, antioxidant status, and histopathological alteration were evaluated. We observed that the significantly increased ulcer index, gastric volume, free and total acidity, malondialdehyde level, and pepsin activity were effectively reduced following treatment with 200 and 300 mg/kg MEVA. The extract also markedly attenuated the reduced activity of superoxide dismutase and reduced glutathione level as well as pH and mucin content in the ulcerated rats. Administration of the extract also significantly attenuates necrosis of the stomach tissue of the ulcerated rats. The results suggested that the MEVA leaf, preferably at 200 and 300 mg/kg body weight, ameliorated aspirin-induced gastric ulceration via antioxidative and H2 receptor antagonist.

Network pharmacology-based identification of protective mechanism of Panax Notoginseng Saponins on aspirin induced gastrointestinal injury.

Aspirin is the first line therapy for cardiovascular and cerebrovascular diseases and is widely used. However aspirin-induced gastrointestinal injury is one of its most common side effect which limits long-term use. Panax Notoginseng Saponins(PNS) which is also used to prevent thrombus may alleviate this side effect according to previous clinical evidences. Owing to the complexity of drug combination, the protective mechanism of PNS on aspirin-induced gastrointestinal injury remains unclear. Therefore, a network pharmacology-based strategy was proposed in this study to address this problem. A network pharmacology approach comprising multiple components, candidate targets of each component, known therapeutic targets, network analysis has been used in this study. Also, we establish aspirin-induced gastrointestinal injury model by the oral administration of aspirin (0.5 g/kg body weight) to verify the predicted targets from network pharmacology. All rats was randomly allocated to control groups (n = 6),aspirin groups (n = 6)and aspirin + PNS groups (n = 6) and conducted H&E staining and ELISA for VEGFA. The comprehensive systematic approach was successfully to identify 5 compounds and 154 candidate targets in PNS and 479 candidate targets in aspirin. After network establishment and analysis, 27 potential targets hit by PNS, aspirin and 6 kind of gastrointestinal diseases were found. The experiments results indicated that aspirin group has visible inflammation and lesions while aspirin + PNS group have not. The higher expression of VEGFA in aspirin + PNS group verified the predicted potential protective targets of PNS. PNS may have protective function for aspirin-induced gastrointestinal injury through increasing VEGFA expression. Network pharmacology strategy may provide a forceful tool for exploring the mechanism of herb medicine and discovering novel bioactive ingredients.

The expression of COX-2 and iNOS in ethanol and aspirin induced gastric ulcer rat models

Aspirin or ethanol induced gastric ulcer rat models are the most frequently used in studies. Aspirin and ethanol induced gastric ulcers through different pathways involving COX-2 and iNOS. The aim of this study was to examine the expression of COX-2 and iNOS in gastric ulcer rat model induced by ethanol and aspirin. Twenty-one Sprague Dawley rats were divided into 7 groups i.e. control group (CA), ethanol 1st day (ED1), ethanol 3rd day (ED3), ethanol 5th day (ED5), aspirin 4th day (AD4), aspirin 6th day (AD6), and aspirin 8th day (AD8). Oral administration of aspirin was at 200mg/kgBW and the 100% ethanol at 1mL/200gBW. Macroscopic and microscopic observations were done to examine the gastric mucosal damage, COX-2 and iNOS expressions. Severe gastric ulcers were observed in ED1 and AD4 groups and mild gastric mucosal damage was observed in ED3, ED5, AD6 and AD8 groups. Microscopically, light erosion was shown by the CA and AD8 groups. Erosion was also shown by ED3, ED5, and AD6 groups. The most severe damage with ulcers and heavier bleeding were shown by the ED1 and AD4 groups. Weak COX-2 expression was found in the CA, while the highest COX-2 expression was found in the ED1. The iNOS expression in the ethanol groups was still increasing until the 5th day (ED5). In the aspirin groups, it reached the peak on the 3rd day (AD6), and already declined on the 5th day (AD8). In conclusion, the damage process of ethanol induced gastric ulcer occurred faster than that by aspirin. The highest COX-2 expression in the ethanol and aspirin groups were shown at the onset begin. iNOS expression in ethanol induced ulcer groups still increased until the 5th day, while in the aspirin induced ulcer groups already declined in the 5th day.

A case of Kawasaki disease presenting as sigmoid colitis

Initial gastrointestinal symptoms might confuse the clinical pictures of some patients with Kawasaki disease (KD) and delay diagnosis and treatment, especially when the patient does not fulfill sufficient diagnostic criteria for KD. Here, we present the case of a 4-year-old boy with KD who complained of severe left abdominal pain and fever alone for the first 6 days. Abdominal ultrasonography showed severe wall thickening localized to the sigmoid colon, and these findings were confirmed by computed tomography and colonoscopy. Microscopic examination of a biopsy specimen revealed non-specific colitis with inflammatory cells in the lamina propria of the sigmoid colon, indicating sigmoid colitis. He subsequently exhibited typical symptoms of KD and was successfully treated with oral administration of aspirin. We suggest that KD should be considered as a differential diagnosis in any child presenting with abdominal symptoms and prolonged fever without definable cause. Abdominal ultrasonography can help evaluate the gastrointestinal complications of KD.