BW755C

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関: 4,5-dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine

4,5-dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine

English Journal

Hypercholesterolemia enhances 15-lipoxygenase-mediated vasorelaxation and acetylcholine-induced hypotension.

Aggarwal NT1, Pfister SL, Campbell WB.Author information 1Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.Retraction inArterioscler Thromb Vasc Biol. 2013 Dec;33(12):e136. AbstractOBJECTIVE: Arachidonic acid (AA) metabolites from 15-lipoxygenase-1 (15-LO-1), trihydroxyeicosatrienoic acid (THETA), and hydroxyepoxyeicosatrienoic acid (HEETA) relax arteries. We studied 15-LO-1 expression, THETA and HEETA synthesis, and their effect on arterial relaxations and blood pressure in hypercholesterolemic nonatherosclerotic rabbits.
Arteriosclerosis, thrombosis, and vascular biology.Arterioscler Thromb Vasc Biol.2008 Dec;28(12):2209-15. doi: 10.1161/ATVBAHA.108.177113. Epub 2008 Oct 2.
OBJECTIVE: Arachidonic acid (AA) metabolites from 15-lipoxygenase-1 (15-LO-1), trihydroxyeicosatrienoic acid (THETA), and hydroxyepoxyeicosatrienoic acid (HEETA) relax arteries. We studied 15-LO-1 expression, THETA and HEETA synthesis, and their effect on arterial relaxations and blood pressure in h
PMID 18832753

Anti-inflammatory activity of Acanthus ilicifolius.

Mani Senthil Kumar KT1, Gorain B, Roy DK, Zothanpuia, Samanta SK, Pal M, Biswas P, Roy A, Adhikari D, Karmakar S, Sen T.Author information 1School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, West Bengal, India.AbstractAcanthus ilicifolius Linn, is a perennial herb (Acanthaceae) widely found in the Sundarban mangroves and is popularly used for its wound healing effects. In the present study an attempt was made to evaluate the anti-inflammatory activity of the Acanthus ilicifolius leaves. The methanolic fraction of Acanthus ilicifolius leaf extract produced significant inhibition of rat paw oedema, when administered both prior to and after carrageenan administration, in a manner similar to BW755C a synthetic cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor. The extract decreased protein exudation and leukocyte migration in the peritoneal fluid, thereby indicating its effectiveness towards inhibiting peritoneal inflammation. It also produced significant inhibition of COX (1 and 2) and 5-LOX activity. Preincubation of the extract inhibited the production of proinflammatory cytokines (TNFalpha and IL-6) in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). The methanolic fraction of the extract was also found to possess significant free radical (DPPH, ABTS, superoxide and hydroxyl radical) scavenging activity. The extract on intraperitoneal administration augmented the endogenous antioxidant status, as evident from the significant increase of ferric reducing ability of plasma (FRAP) and total peroxyl radical trapping activity of plasma (TRAP).
Journal of ethnopharmacology.J Ethnopharmacol.2008 Oct 30;120(1):7-12. doi: 10.1016/j.jep.2008.07.024. Epub 2008 Jul 25.
Acanthus ilicifolius Linn, is a perennial herb (Acanthaceae) widely found in the Sundarban mangroves and is popularly used for its wound healing effects. In the present study an attempt was made to evaluate the anti-inflammatory activity of the Acanthus ilicifolius leaves. The methanolic fraction of
PMID 18703126

15-Lipoxygenase metabolites contribute to age-related reduction in acetylcholine-induced hypotension in rabbits.

Aggarwal NT1, Gauthier KM, Campbell WB.Author information 1Dept. of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.AbstractArachidonic acid (AA) metabolites from the 15-lipoxygenase-1 (15-LO-1) pathway, trihydroxyeicosatrienoic acids (THETAs) and hydroxy-epoxyeicosatrienoic acids (HEETAs), are endothelium-derived hyperpolarizing factors (EDHFs) and relax rabbit arteries. Rabbit vascular 15-LO-1 expression, THETA and HEETA synthesis, and nitric oxide and prostaglandin-independent relaxations to acetylcholine (ACh) and AA decreased with age (neonates to 16-wk-old). We characterized age-dependent ACh-hypotensive responses in vivo in 1-, 4-, 8-, and 16-wk-old rabbits and the contribution of THETAs and HEETAs to these responses. In anesthetized rabbits, blood pressure responses to ACh (4-4,000 ng/kg) were determined in the presence of vehicle or various inhibitors. ACh responses decreased with age (P > 0.001). In the absence or presence of N(omega)-nitro-l-arginine methyl ester (l-NAME) and indomethacin (Indo), maximum responses in 1 (-54.7 +/- 7.4 and -37.9 +/- 3.9%)- and 4 (-48.8 +/- 2.4 and -35.5 +/- 7.8%)-wk-old rabbits were higher than 8 (-30.0 +/- 2.8 and -26.6 +/- 4.4%)- and 16 (-36.7 +/- 3.5 and -27.3 +/- 10%)-wk-old rabbits. A lipoxygenase inhibitor, BW755C, reduced THETA and HEETA synthesis in mesenteric arteries. In the presence of Indo and N(omega)-nitro-l-arginine, ACh relaxations were reduced by BW755C to a greater extent in the mesenteric arteries from the younger rabbits. In 4-wk-old rabbits treated with l-NAME and Indo, the maximum ACh hypotension was reduced by the potassium channel inhibitors apamin and charybdotoxin to -6.9 +/- 0.9%, by apamin alone to -19.5 +/- 1.4%, and by BW755C to -18.8 +/- 3.5%. The present study indicates that the age-related decrease in ACh-induced hypotension is mediated by the decreased synthesis of the 15-LO-1 metabolites THETAs and HEETAs.
American journal of physiology. Heart and circulatory physiology.Am J Physiol Heart Circ Physiol.2008 Jul;295(1):H89-96. doi: 10.1152/ajpheart.00054.2008. Epub 2008 May 2.
Arachidonic acid (AA) metabolites from the 15-lipoxygenase-1 (15-LO-1) pathway, trihydroxyeicosatrienoic acids (THETAs) and hydroxy-epoxyeicosatrienoic acids (HEETAs), are endothelium-derived hyperpolarizing factors (EDHFs) and relax rabbit arteries. Rabbit vascular 15-LO-1 expression, THETA and HEE
PMID 18456739