Disease relevance of AI3-51108

• Rutaecarpine (Rut) has been shown to induce hypotension and vasorelaxation [1].
• In the present study, the effect of rutaecarpine on cardiac anaphylaxis was examined [2].
• Previous investigations have shown that calcitonin gene-related peptide (CGRP) protects against myocardial ischemia-reperfusion injury and that rutaecarpine activates vanilloid receptors to evoke CGRP release [3].
• Rutaecarpine at the concentration of 1 microM also inhibited the sinus tachycardia [2].
• These results suggest that rutaecarpine has an effective anti-platelet effect in vivo and that it may be a potential therapeutic agent for arterial thrombosis, but it must be assessed further for toxicity [4].

High impact information on AI3-51108

• Stimulation of calcitonin gene-related peptide synthesis and release: mechanisms for a novel antihypertensive drug, rutaecarpine [5].
• The IC50 value for binding of 7,8-dehydrorutaecarpine was estimated to approximately 7 nM indicating a high-affinity interaction, whereas rutaecarpine appeared less active (IC50 approximately 110 nM) [6].
• Interactions of rutaecarpine alkaloids with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver [6].
• Under current-clamp configuration, rutaecarpine prolonged action potential duration in NG108-15 cells [7].
• Vasorelaxing action of rutaecarpine: effects of rutaecarpine on calcium channel activities in vascular endothelial and smooth muscle cells [1].

Chemical compound and disease context of AI3-51108

• These results suggest that rutaecarpine protects against myocardial ischemia-reperfusion injury in rats and that the protective effects of rutaecarpine are related to activation of capsaicin-sensitive sensory nerves via activating vanilloid receptors [8].
• These findings suggest that ER and its constituents, evodiamine and rutaecarpine, may be effective for IgE-induced allergic diseases such as atopic dermatitis and rhinitis [9].

Biological context of AI3-51108

• We have examined both the hypotensive effect and the mechanism of intracellular Ca++ regulation, underlying rutaecarpine (Rut)-induced vasodilatation [10].
• The metabolite profile and kinetic properties of rutaecarpine hydroxylation by human P450s provide important information relevant to the clinical application of rutaecarpine and E. rutaecarpa [11].
• Pretreatment with rutaecarpine (10 or 30 microM) significantly increased CGRP release concomitantly with decrease in antigen-challenged vasoconstriction, which was abolished by CGRP8-37 (10 microM) or capsazepine (10 microM) [12].
• Continuous infusion of rutaecarpine (5 microg/g/min) also significantly increased the bleeding time 1 [4].
• Mechanism of inhibition of platelet aggregation by rutaecarpine, an alkaloid isolated from Evodia rutaecarpa [13].

Anatomical context of AI3-51108

• Rutaecarpine (Rut) can relax vascular smooth muscle via stimulation of calcitonin gene-related peptide (CGRP) release by activation of VR1 [5].
• The vasorelaxing action of rutaecarpine: direct paradoxical effects on intracellular calcium concentration of vascular smooth muscle and endothelial cells [10].
• Four oxidation metabolites of rutaecarpine were prepared from 3-methylcholanthrene-treated rat liver microsomes [14].
• The protective effects of rutaecarpine on gastric mucosa injury in rats [15].
• Inhibition of UVA irradiation-modulated signaling pathways by rutaecarpine, a quinazolinocarboline alkaloid, in human keratinocytes [16].

Associations of AI3-51108 with other chemical compounds

• Evodiamine and rutaecarpine produced transient positive inotropic and chronotropic effects on the guinea-pig isolated atria, followed by a desensitizing effect to additional administration [17].
• When rutaecarpine was incubated with rat liver microsomes in the presence of an NADPH-generating system, five metabolites were detected by UV and mass spectral analyses [18].
• These effects of rutaecarpine were completely abolished by capsazepine (38 mg/kg, s.c.), a competitive vanilloid receptor antagonist, or by pretreatment with capsaicin (50 mg/kg, s.c.), which selectively depletes transmitters in capsaicin-sensitive sensory nerves [8].
• In human liver microsomes, 1 microM rutaecarpine caused 98, 91, and 77% decreases of EROD, MROD, and phenacetin O-deethylation activities, respectively [19].
• In contrast, less than 15% inhibition of AHH, tolbutamide hydroxylation, chlorzoxazone hydroxylation, and NFO activities were observed in the presence of 1 microM rutaecarpine [19].

Gene context of AI3-51108

• These results indicated that multiple hepatic P450s including CYP1A2, CYP2D6, and CYP3A4 participate in rutaecarpine hydroxylations [11].
• Among recombinant P450s, CYP1A1 had the highest rutaecarpine hydroxylation activity [11].
• To identify the major human cytochrome P450 (P450) participating in rutaecarpine oxidative metabolism, human liver microsomes and bacteria-expressed recombinant human P450 were studied [11].
• The major metabolite 10-hydroxyrutaecarpine decreased CYP1A1, CYP1A2, and CYP1B1 activities with respective IC(50) values of 2.56 +/- 0.04, 2.57 +/- 0.11, and 0.09 +/- 0.01 muM, suggesting that product inhibition might occur during rutaecarpine hydroxylation [11].
• CYP1A2 and CYP2C9 played minor roles in the metabolism of rutaecarpine [20].

Analytical, diagnostic and therapeutic context of AI3-51108

• Characterization of in vitro metabolites of rutaecarpine in rat liver microsomes using liquid chromatography/tandem mass spectrometry [21].
• These results suggest that rutaecarpine enhances preservation with cardioplegia in guinea-pig hearts and that the protective effects of rutaecarpine are due to stimulation of endogenous CGRP release via activating vanilloid receptors [3].
• Rats were pretreated with rutaecarpine 10 min before the experiment, and then the left main coronary artery of rat hearts was subjected to 60-min occlusion followed by 3-h reperfusion [8].
• The induction of P450 1A and 2B by rutaecarpine was confirmed by Western immunoblotting [18].
• Oral administration to male ICR mice of rutaecarpine for 3 consecutive days induced liver P450 1A-, 2B- and 2E1-selective monooxygenase activities [18].

References