thromboxane-b2 and ferulic-acid

Ferulic acid (FA) produces protective effects against cardiovascular dysfunctions. However, the mechanisms of FA is still not known. Here we examined the antithrombotic effects of FA and its potential mechanisms. Anticoagulation assays and platelet aggregation was evaluated in vitro and in vivo. Thromboxane B2 (TXB2), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate (cGMP) was determined using enzyme immunoassay kits. Nitric oxide (NO) production was measured using the Griess reaction. Protein expression was detected by Western blotting analysis. Oral administration of FA prevented death caused by pulmonary thrombosis and prolonged the tail bleeding and clotting time in mice,while, it did not alter the coagulation parameters, including the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). In addition, FA (50-200 µM) dose-dependently inhibited platelet aggregation induced by various platelet agonists, including adenosine diphosphate (ADP), thrombin, collagen, arachidonic acid (AA), and U46619. Further, FA attenuated intracellular Ca(2)(+) mobilization and TXB2 production induced by the platelet agonists. FA increased the levels of cAMP and cGMP and phosphorylated vasodilator-stimulated phosphoprotein (VASP) while decreased phospho-MAPK (mitogen-activated protein kinase) and phosphodiesterase (PDE) in washed rat platelets, VASP is a substrate of cyclic nucleotide and PDE is an enzyme family responsible for hydrolysis of cAMP/cGMP. These results suggest that antithrombotic activities of FA may be regulated by inhibition of platelet aggregation, rather than through inhibiting the release of thromboplastin or formation of thrombin. The mechanism of this action may involve activation of cAMP and cGMP signaling.

Topics: Animals; Blood Coagulation; Calcium; Cell Adhesion Molecules; Coumaric Acids; Cyclic AMP; Cyclic GMP; Fibrinolytic Agents; Hemorrhage; Intracellular Space; Male; Mice; Microfilament Proteins; Mitogen-Activated Protein Kinases; Nitric Oxide; Phosphoproteins; Phosphoric Diester Hydrolases; Phosphorylation; Rats; Signal Transduction; Superoxides; Thrombosis; Thromboxane B2

Ferulic acid (FA), a phytochemical constituent, has antihypertensive effects, but a detailed understanding of its effects on vascular function remains unclear. The vasoreactivity of FA was assessed using aortic rings isolated from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR).. The effects of FA (10(-5) to 10(-3) mol/L) on vasodilatory responses were evaluated based on contractile responses induced by phenylephrine (10(-6) mol/L) in thoracic aortic rings from male WKY rats and SHR. Basal nitric oxide (NO) bioavailability in the aorta was determined from the contractile response induced by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/L). The effects of FA on the production of NADPH-dependent superoxide anion were examined in SHR aortas. The impact of hydroxyhydroquinone, a generator of superoxide anions, on the FA-induced enhancement in acetylcholine-stimulated vasodilation was also investigated.. The FA (10(-3) mol/L)-induced relaxation was partially blocked by removal of the endothelium or by pretreating SHR aortas with L-NAME. FA increased NO bioavailability, and decreased NADPH-dependent superoxide anion levels in SHR aortas. Ferulic acid improved acetylcholine-induced endothelium-dependent vasodilation in SHR, but not in WKY. Furthermore, the simultaneous addition of hydroxyhydroquinone significantly inhibited the increase in acetylcholine-induced vasodilation by FA.. Ferulic acid restores endothelial function through enhancing the bioavailability of basal and stimulated NO in SHR aortas. The results explain, in part, the mechanisms underlying the effects of FA on blood pressure (BP) in SHR.

Topics: Acetylcholine; Animals; Antihypertensive Agents; Aorta; Coumaric Acids; Cyclic GMP; Endothelium, Vascular; Hydroquinones; Hypertension; Male; NADP; NG-Nitroarginine Methyl Ester; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Superoxides; Thromboxane B2; Vasodilation

To investigate the ameliorative effects of sodium ferulate (SF) on acetic acid-induced colitis and their mechanisms in rats.. The colitis model of Sprague-Dawley rats was induced by intracolon enema with 8% (V/V) of acetic acid. The experimental animals were randomly divided into model control, 5-aminosalicylic acid therapy group and three dose of SF therapy groups. The 5 groups were treated intracolonically with normal saline, 5-aminosalicylic acid (100 mg x kg(-1)), and SF at the doses of 200, 400 and 800 mg x kg(-1) respectively and daily (8:00 am) for 7 days 24 h following the induction of colitis. A normal control group of rats clystered with normal saline instead of acetic acid was also included in the study. Pathological changes of the colonic mucosa were evaluated by the colon mucosa damage index (CMDI) and the histopathological score (HS). The insulted colonic mucosa was sampled for a variety of determinations at the end of experiment when the animals were sacrificed by decapitation. Colonic activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), and levels of malondialdehyde (MDA) and nitric oxide (NO) were assayed with ultraviolet spectrophotometry. Colonic contents of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) were determined by radioimmunoassay. The expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2) and nuclear factor kappa B (NF-kappaB) p65 proteins in the colonic tissue were detected with immunohistochemistry.. Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels, PGE2 and TXB2 contents, as well as the expressions of iNOS, COX-2 and NF-kappaB p65 proteins in the colonic mucosa, although the colonic SOD activity was significantly decreased compared with the normal control (CMDI: 2.9+/-0.6 vs 0.0+/-0.0; HS: 4.3+/-0.9 vs 0.7+/-1.1; MPO: 98.1+/-26.9 vs 24.8+/-11.5; MDA: 57.53+/-12.36 vs 9.21+/-3.85; NO: 0.331+/-0.092 vs 0.176+/-0.045; PGE2: 186.2+/-96.2 vs 42.8+/-32.8; TXB2: 34.26+/-13.51 vs 8.83+/-3.75; iNOS: 0.365+/-0.026 vs 0.053+/-0.015; COX-2: 0.296+/-0.028 vs 0.034+/-0.013; NF-kappaB p65: 0.314+/-0.026 vs 0.039+/-0.012; SOD: 28.33+/-1.17 vs 36.14+/-1.91; P<0.01). However, these parameters were found to be significantly ameliorated in rats treated locally with SF at the given dose protocols, especially at 400 mg x kg(-1) and 800 mg x kg(-1) doses (CMDI: 1.8+/-0.8, 1.6+/-0.9; HS: 3.3+/-0.9, 3.1+/-1.0; MPO: 63.8+/-30.5, 36.2+/-14.2; MDA: 41.84+/-10.62, 37.34+/-8.58; NO: 0.247+/-0.042; 0.216+/-0.033; PGE2: 77.2+/-26.9, 58.4+/-23.9; TXB2: 18.07+/-14.83; 15.52+/-8.62; iNOS:0.175+/-0.018, 0.106+/-0.019; COX-2: 0.064+/-0.018, 0.056+/-0.014; NF-kappaBp65: 0.215+/-0.019,0.189+/-0.016; SOD: 32.15+/-4.26, 33.24+/-3.69; P<0.05-0.01). Moreover, a therapeutic dose protocol of 800 mg x kg(-1) SF was observed as effective as 100 mg x kg(-1) of 5-ASA in the amelioration of colonic mucosal injury as evaluated by CMDI and HS.. Administration of SF intracolonically may have significant therapeutic effects on the rat model of colitis induced by acetic acid enema, which was probably due to the mechanism of antioxidation, inhibition of arachidonic acid metabolism and NF-kappaB expression.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis; Coumaric Acids; Cyclooxygenase 2; Dinoprostone; Female; Intestinal Mucosa; Isoenzymes; Male; NF-kappa B; Nitric Oxide Synthase; Oxidative Stress; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Thromboxane B2; Transcription Factor RelA

In the present study, the influence of sodium ferulate (SF) on hypotensive effect and urinary excretion of TXB2 after captopril (CAP) was observed in 44 patients with essential hypertension. A single oral dose of CAP (50 mg) decreased mean arterial pressure (MAP) from 16.25 +/- 0.85 to 13.65 +/- 1.14 kPa, n = 28, (P less than 0.01), and increased urinary TXB2 excretion significantly from 119.12 +/- 57.12 to 183.32 +/- 78.61 pg/min, n = 16, (P less than 0.05). The administration of SF 300 mg/d for one day did not affect the MAP. CAP in combination with SF induced a decrease both in MAP from 16.33 +/- 1.14 to 13.83 +/- 1.77 kPa, n = 16, (P less than 0.01) and urinary TXB2 excretion from 155.89 +/- 69.64 to 133.43 +/- 60.01 pg/min, n = 16, (P greater than 0.05) though the latter was not so significant. Compared with the administration of CAP alone, the combination of CAP and SF induced stronger hypotensive effect (P less than 0.05) and the increased urinary TXB2 excretion could be inhibited by SF, but the inhibition to angiotensin converting enzyme was the same. These results suggested that the increased urinary TXB2 excretion by CAP can be inhibited and the hypotensive effect of CAP is potentiated by SF in essential hypertensive patients.

Topics: Antihypertensive Agents; Captopril; Coumaric Acids; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Peptidyl-Dipeptidase A; Thromboxane B2

Sodium ferulate (SF) is one of the antiplatelet ingredients in Radix Angleica sinensis. The effect of SF on 14C-arachidonic acid metabolism in washed intact rabbit platelets was studied with radiochromatography and radioautography. SF (0.1-3.2 mmol/L) inhibited the generation of platelet thromboxane B2 in a dose-dependent manner (reduced by 16.7-93.8%) and the IC50 was shown to be 0.762 mmol/L. Simultaneously with the reduction of TXB2 generation, the formation of PGE2 and PGF2 alpha was also reduced significantly after treatment with SF. Using radioimmunoassay SF (0.145-2.32 mmol/L) was found to inhibit rabbit platelet TXB2 formation in a dose-dependent manner. SF (0.58-2.32 mmol/L) also suppressed aortic tissue 6-keto-PGF1 alpha generation in rabbits. At the same concentrations the inhibitory effect of SF on platelet TXB2 formation was greater than that on aortic tissue 6-keto-PGF1 alpha generation. These results indicate that the cyclo-oxygenase activity may be inhibited by SF.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticoagulants; Aorta; Arachidonic Acids; Blood Platelets; Coumaric Acids; Dinoprost; Dinoprostone; Male; Rabbits; Rats; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticoagulants; Cinnamates; Coumaric Acids; Lung; Microsomes; Swine; Thromboxane B2; Thromboxane-A Synthase

Topics: Animals; Arachidonic Acids; Blood Platelets; Cinnamates; Coumaric Acids; Dinoprost; Dinoprostone; Platelet Aggregation; Rabbits; Thromboxane B2