Disease relevance of Esculetin dimethyl ether

• The overexpression of CYP2C45 in chicken hepatoma cells leghorn male hepatoma (LMH) led to increased scoparone metabolism [1].
• A high-performance liquid chromatography method that utilized fluorescence detection (HPLC-FL) of mycolic acid 6,7-dimethoxycoumarin esters was developed to identify Mycobacterium tuberculosis (MTB) and M. avium complex (MAC) directly from fluorochrome stain smear-positive sputum specimens and young BACTEC 12B cultures [2].
• Scoparone (5-100 muM) had no cytotoxic effect in unstimulated cells and concentration-dependently reversed PMA-induced toxicity in the cells stimulated with PMA [3].
• Inhibition of cytokine-mediated nitric oxide synthase expression in rat insulinoma cells by scoparone [4].
• Stimulation of melanogenesis by scoparone in B16 melanoma cells [5].

High impact information on Esculetin dimethyl ether

• OBJECTIVE: Scoparone (6,7-dimethoxycoumarin), a coumarin isolated from a hypolipidaemic Chinese herb Artemisia scoparia, has vasodilator and antiproliferative activities and possesses free radical scavenging properties in vitro [6].
• In the scoparone treated rabbits, the proportion of the aortic surface area covered with macroscopic plaques was 30%, and the thickness of the tunica intima 17%, of that of the non-scoparone treated hyperlipidaemic diabetic rabbits [6].
• Biotransformation of scoparone used to monitor changes in cytochrome P450 activities in primary hepatocyte cultures derived from rats, hamsters and monkeys [7].
• Rat hepatocytes appeared to metabolize scoparone 7 to 10 times slower than those of hamsters and monkeys [7].
• In hepatocyte monolayers of all three species the loss of P450 was paralleled by a decrease in total scoparone metabolism [7].

Chemical compound and disease context of Esculetin dimethyl ether

• Biotransformation of esculetin with E. coli expressing POMT-9 generated scopoletin, isoscopoletin, and scoparone at 30.3, 21, and 31 microM respectively [8].
• Presence of scoparone significantly protected interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma)-mediated cytotoxicity of RINm5F, a rat insulinoma cell line, and preserved glucose-stimulated insulin secretion in rat pancreatic islets [4].

Biological context of Esculetin dimethyl ether

• Oxidative hydrolysis of scoparone by cytochrome p450 CYP2C29 reveals a novel metabolite [9].
• The concentrations of scoparone used in this study did not affect cell viability [10].
• Hepatocyte culture performance was monitored for 51 h by measuring viability, cytochrome P-450 maintenance, dealkylation of scoparone and ethylmorphine, and glucuronidation of phenol red [11].
• Scoparone was found to cause the increase in coronary flow and heart rate, but did not affect cardiac output, left ventricular pressure or left ventricular work in the isolated perfused heart [12].
• Biocontrol of aflatoxins B1, B2, G1, G2, and fumonisin B1 with 6,7-dimethoxycoumarin, a phytoalexin from Citrus sinensis [13].

Anatomical context of Esculetin dimethyl ether

• Most likely, in hamster and possibly in monkey hepatocyte cultures the different P450s involved in scoparone metabolism decrease at unequal rates [7].
• Liver microsomes from hamster not treated with P450 inducers oxidized scoparone much more efficiently than liver microsomes of untreated rats [14].
• Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries [3].
• In the current studies, we examined the effects of scoparone on inhibiting lipopolysaccharide (LPS)-induced TF expression in cultured human umbilical vein endothelial cells (HUVECs) [10].
• Scoparone inhibits PMA-induced IL-8 and MCP-1 production through suppression of NF-kappaB activation in U937 cells [3].

Associations of Esculetin dimethyl ether with other chemical compounds

• The oxidative removal of two different methyl groups from scoparone by a cytochrome P-450-mediated reaction proceeds with greater velocity for the 6-methyl group than for the 7-methyl group [15].
• Regioselective 7-demethylation of scoparone is regularly employed as an indicator of phenobarbital-like induction of rat liver cytochrome P450 isoform CYP2B1, e.g., by the antiepileptic drug phenytoin [9].
• Emodin (3 x 10(-7)-10(-4) M) and scoparone (10(-6)-3 x 10(-4) M) also dose dependently suppressed the responses of human mononuclear cells to phytohemagglutinin and mixed lymphocyte reaction [16].
• We compared the effect of scoparone on the mononuclear cell response to genistein, a specific inhibitor of protein tyrosine kinase and demonstrated the non-additivity and cross-desensitization of the two compounds [17].
• No changes in the level of IP3 were detected in response to the treatment with the G-protein activators cholera toxin or mastoparan, although the HR was observed in response to these compounds as determined by the scoparone synthesis [18].

Gene context of Esculetin dimethyl ether

• Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in LPS-stimulated RAW264.7 cells [19].
• Scoparone from Artemisia capillaris inhibits the release of inflammatory mediators in RAW 264.7 cells upon stimulation cells by interferon-gamma Plus LPS [19].
• These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and PGE2 in macrophages by inhibiting iNOS and COX-2 expression [19].
• Cyp2c29-dependent 6-demethylation of scoparone resulted in the formation of isoscopoletin, an intermediate which is susceptible to further oxidation [9].
• The molecular mechanism by which scoparone inhibited iNOS gene expression appeared to involve the inhibition of NF-kappaB activation [4].

Analytical, diagnostic and therapeutic context of Esculetin dimethyl ether

• The aim of the study was to investigate the morphological effects of scoparone in the antiatherogenic process in vivo by using hyperlipidaemic diabetic rabbits as an animal model [6].
• The consecutive administration of the scoparone to the same animal is followed by collecting the 14CO2 exhaled (breath test) [15].
• The proliferative response of mononuclear cells to mixed lymphocyte reaction was also reduced by scoparone (10(-5) to 10(-4) M) [17].
• The scoparone concentration in the inoculated sites of hot dipped fruit started to rise 24 h after treatment and reached a level sufficient to inhibit the pathogen within 2 days after treatment [20].
• Pharmacokinetics of a novel anti-asthmatic, scoparone, in the rabbit serum assessed by a simple HPLC method [21].

References