Evaluation of the hypolipidemic activity of 6,7-dimethoxycoumarin on placental tissue factor mRNA expression in experimental anti-phospholipid syndrome

Abstract

Background:Anti-phospholipid syndrome is a thrombogenic and systemic autoimmune disorder that influences fetal life throughout gestation period. Over expression of tissue factor on the surface of monocyte(s) is reported to be a major causative agent in inducing anti-phospholipid antibody-mediated placental thrombosis and fetal loss in pregnant women. The over expression of tissue factor is proposed to be due to high levels of blood cholesterol and oxidized lipoproteins.Objective:In this study, we report the lipid-lowering property and anti-tissue factor activity of one of the naturally occurring coumarin derivates 6,7-dimethoxycoumarin, found aplenty in Chinese medicinal plant Artemisia scoparia, and its effect on tissue factor mRNA expression in experimental anti-phospholipid syndrome.Materials and Methods:Adult female mice were immunized with cardiolipin and beta-2-glycoprotein-1 to induce experimental anti-phospholipid syndrome. Female mice with high titer of aCL were allowed to mate with male, and the female mice were treated with 6,7-dimethoxycoumarin on a daily dose of 5 mg/kg body weight from day 3 to day 15 of gestation. On day 18 of pregnancy, all the animals were dissected to measure biochemical parameters in blood, and TF mRNA expression levels were measured in placenta.Results:Treatment with 6,7-dimethoxycoumarin significantly reduced the levels of cholesterol and plasma lipids by its potent hypolipidemic property, which eventually reduced the over-expression tissue factor at mRNA levels in placenta. We believe that further studies in animal model would reveal the potential therapeutic properties of 6,7-dimethoxycoumarin against anti-phospholipid syndrome.Conclusion:The 6,7-dimethoxycoumarin is capable to reduce the expression of TF in placenta at the mRNA level and thrombus generation indirectly by its potent anti-TF and anti-oxidant activities.

Coumarins: The Antimicrobial agents

“…33 Al-Amiery et al have synthesized 4-[(5-mercapto-4-phenyl-4H-1,2,4triazol-3-yl)-methoxy]-2H-chromen-2-one as coumarin derivatives and their antifungal activity was determined based on the growth inhibition rates of the mycelia of strains of Aspergillus niger and Candida albicans in Potato Dextrose Broth medium (PDB) against concentrations ranging from 10 to 100µgml -1 . Two compounds (5,6) showed good activity as antifungals against fluconazole standard drug. 34 Behrami et al synthesized 8-amino-4,7-dihydroxy-chromen-2-one coumarin derivatives.…”

“…There are a number of reports that natural and synthetic Coumarin derivatives posses antimicrobial activity. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Novobiocin and Chlorobiocin are established antimicrobials containing a Coumarin (i.e.2H-1-benzopyran-2-ones) skeleton, there are many Coumarin derivatives which have been reported for anticoagulant, anti-inflammatory, anti-HIV, antioxidant, anti-allergic, anti-cancer, anti proliferative and antiviral activities. [15][16][17] It was found that when one biodynamic heterocyclic system was coupled with another heterocyclic system, enhanced biological activity was produced.…”

Synthesis, Docking and Antimicrobial Activity of Some New Coumarin Incorporated Thiazole Derivatives

“…Numerous reports state that synthetic and natural Coumarin derivatives own antimicrobial activity [2][3][4][5][6]. Chlorobiocin and Novobiocin are acknowledged antimicrobials consisting of Coumarin (i.e.2H-1-benzopyran-2-ones) skeleton.…”