7-Methoxyisoflavone

7-Methoxyisoflavone suppresses vascular endothelial inflammation by inhibiting the expression of endothelial adhesion molecules

Endothelial cells (ECs) are vital regulators of inflammatory processes, there is the potential for inhibition of EC inflammation to be a therapeutic target in chronic inflammatory diseases. This study aimed to investigate the effect of 7-methoxyisoflavone (7-Mif) on endothelial inflammation. Our results showed that 7-Mif have no cytotoxicity on HUVECs. Pretreatment with 5 米M, 10 米M and 50 米M 7-Mif significantly reduced IL-1汕-induced ICAM-1 (28.1% ㊣ 4.1%, 25.9 ㊣ 2.5% and 32.0% ㊣ 3.2%, respectively) and VCAM-1 (48.0% ㊣ 5.6%, 40.1 ㊣ 3.1% and 39.6% ㊣ 3.1%, respectively) mRNA expression. And pretreatment with 10 米M and 50 米M 7-Mif significantly reduced IL-1汕-induced ICAM-1 (45.1% ㊣ 4.4% and 33.6 ㊣ 4.4%, respectively) and VCAM-1 (53.0% ㊣ 3.7% and 53.7 ㊣ 5.1%, respectively) protein levels. Furthermore, pretreatment with 50 米M 7-Mif inhibited monocyte-endothelial cell adhesion (50.2% ㊣ 4.2%). Mechanistically, our results showed that 7-Mif reversed IL-1汕-induced NF-百B activation and p65 translocation to the nucleus, therefore inhibiting endothelial cell inflammation. In addition, we confirmed that 7-Mif 10 mg/kg and 20 mg/kg reduced LPS-induced ICAM-1 (47.3% ㊣ 1.3% and 39.0% ㊣ 3.2%, respectively) and VCAM-1 (56.5 ㊣ 2.8% and 47.8 ㊣ 4.3%, respectively) expression and attenuated inflammatory injury in mice. In conclusion, we showed the inhibitory effect of 7-Mif on endothelial inflammation by suppressing the expression of endothelial adhesion molecules and monocyte adhesion. Our data illustrated that 7-Mif could positively regulate the process of endothelial inflammation.

7-Methoxyisoflavone ameliorates atopic dermatitis symptoms by regulating multiple signaling pathways and reducing chemokine production

7-Met, a derivative of soybean isoflavone, is a natural flavonoid compound that has been reported to have multiple signaling pathways regulation effects. This study investigated the therapeutic effects of 7-Met on mice with atopic dermatitis induced by fluorescein isothiocyanate (FITC), or oxazolone (OXZ). 7-Met ameliorated FITC or OXZ-induced atopic dermatitis symptoms by decreasing ear thickness, spleen index, mast cell activation, neutrophil infiltration and serum IgE levels in female BALB/c mice. In FITC-induced atopic dermatitis mice, 7-Met reduced Th1 cytokines production and regulated Th1/Th2 balance by downregulating the secretion of thymic stromal lymphopoietin (TSLP) via inactivation of the NF-百B pathway. In OXZ-induced atopic dermatitis, 7-Met functioned through the reduction of Th17 cytokine production. Our study showed that 7-Methoxyisoflavone alleviated atopic dermatitis by regulating multiple signaling pathways and downregulating chemokine production.

UPLC-ESI-Q-TOF-MS(E) identification of urinary metabolites of the emerging sport nutrition supplement methoxyisoflavone in human subjects

Methoxyisoflavone (5-methyl-7-methoxyisoflavone) is a synthetic isoflavone used by bodybuilders for its ergogenic properties. A recent study demonstrated that methoxyisoflavone metabolites can induce false-positive results in urinary immunoassay screening tests for cannabinoids, and only one metabolite has been identified. To improve the knowledge on the metabolic pathways of methoxyisoflavone, ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF) was applied. Urine samples were obtained from methoxyisoflavone regular users. After enzymatic hydrolysis and liquid-liquid extraction, the samples were analyzed by UPLC-Q-TOF fitted with an electrospray ionization source (ESI) operating under positive ion mode. Mass data were acquired with the MS(E) method. Five metabolites were identified. Those were divided into two metabolic pathways, depending on whether the B ring hydroxylation was preceded or not by the O-demethylation of the methoxy group. The MS(E) mass spectra of methoxyisoflavone and its metabolites are specific of isoflavones structures and revealed 1,3 retro Diels-Alder fragmentation and double CO loss. Losses of small neutral molecules CO and H2O, and radical CH3, typical of flavonoids, were also observed. This study illustrates the capacity of the sensitive UPLC-Q-TOF analytical system, combined with the MS(E) method of collection of fragmentation data, to rapidly elucidate the unknown xenobiotics metabolism.

Demethylation of 7-methoxyisoflavone by Penicillium cyclopium

An investigation on the metabolic pathways of synthetic isoflavones by gas chromatography coupled to high accuracy mass spectrometry

Rationale: Isoflavones are a group of flavonoids that may be of interest in sport doping because they can be used by athletes in the recovery periods after the administration of anabolic steroids, with the aim of increasing the natural production of luteinizing hormone (LH) and, consequently, the biosynthesis of endogenous androgens.
Methods: The in vivo metabolism of methoxyisoflavone (5-methyl-7-methoxyisoflavone) and ipriflavone (7-isopropoxyisoflavone), respectively present in a dietary supplement and in a pharmaceutical preparation, was investigated. The study was carried out by the analysis of urinary samples collected from male Caucasian subjects before, during and after the oral administration of methoxyisoflavone or ipriflavone. After enzymatic hydrolysis and liquid-liquid extraction, all urinary samples were analyzed by gas chromatography/quadrupole time-of-flight (qTOF MS system/qTOF) electron ionization mass spectrometry (EI-MS).
Results: Eight metabolites of methoxyisoflavone and six metabolites of ipriflavone were isolated. The corresponding accurate mass spectra are specific for isoflavone structures and revealed also a retro-Diels-Alder fragmentation.
Conclusions: When excreted in large amounts, the urinary metabolites of methoxyisoflavone and ipriflavone can be traced to potential confounding factors in doping analysis. As methoxyisoflavone and ipriflavone have been shown to inhibit the enzyme aromatase, thus interfering with the normal metabolic pathways of testosterone, the detection of their intake, by screening for the presence of their main metabolites in urine, might be helpful in routine doping control analysis.