Glycosidase inhibitory flavonoids from Sophora flavescens. PUMID/DOI：16462036 Biol. Pharm. Bull., 2006, 29(2):302-5. The methanol extract of Sophora flavescens showed a potent glycosidase inhibitory activity. Active components were identified as well-known flavonoid antioxidants: kushenol A (1), (-)-kurarinone (2), sophoraflavanone G (3), 2'-Methoxykurarinone (4), kurarinol (5), 8-prenylkaempferol (6), isoxanthohumol (7), kuraridin (8) and maackian (9). All flavonoids were effective inhibitors of alpha-glucosidase and beta-amylase. Interestingly, lavandulylated flavanones 1-5 had strong alpha-glucosidase inhibitory activities, with IC(50) values of 45 microM, 68 microM, 37 microM, 155 microM and 179 microM, respectively. Protein tyrosine phosphatase 1B inhibitory activity of lavandulyl flavonoids from roots of Sophora flavescens. PUMID/DOI：24782228 Planta Med., 2014, 80(7):557-60. Protein tyrosine phosphatase 1B is a non-transmembrane protein tyrosine phosphatase and major negative regulator in insulin signaling cascades, and much attention has been paid to protein tyrosine phosphatase 1B inhibitors as potential therapies for diabetes. The screening of a natural compound library led to the discovery of five lavandulyl flavonoids, which were isolated from the roots of Sophora flavescens, as novel PTP1B inhibitors: kuraridin (1), norkurarinone (2), kurarinone (3), 2'-methoxykurarinone (4), and kushenol T (5). The three most potent compounds, 1, 2, and 4 (IC50 30?μM), were demonstrated to be noncompetitive inhibitors of protein tyrosine phosphatase 1B based on a kinetic analysis, and they exhibited different inhibitory selectivities against four homologous protein tyrosine phosphatases (T cell protein tyrosine phosphatase, vaccinia H1-related phosphatase, and Src homology domain 2-containing protein tyrosine phosphatases 1 and 2). Compounds 1, 2, and 4 also exhibited cellular activity in the insulin signaling pathway by increasing the insulin-stimulated Akt phosphorylation level in human hepatocellular liver carcinoma HepG2 cells, suggesting their potential for new anti-insulin-resistant drug developments. Trypanocidal Flavonoids from Sophora flavescens PUMID/DOI： Natural Medicines, 2003, 57:253-5. The acetone extract of Sophora flavescens Aiton (Leguminosae) exhibited lethal activity against Trypanosoma cruzi. Column chromatographic separation of the extract guided by trypanocidal activity afforded a new prenylated flavanone (4), together with nine known flavonoids: sophoraflavanone G (1), (-) -kurarinone (2), kushenol L (3), 2'-Methoxykurarinone, (5), 7,4′-dihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone (6), leachianone A (7), 8-prenylnaringenin (8), noranhydroicaritin (9) and alopecurone G (10). The structure of the new flavanone 4 was determined on the basis of spectroscopic analyses. The minimum lethal concentrations of these compounds against epimastigotes of T. cruzi were 3.7 μM (1), 14 μM (2), 7.1 μM (3), 7.2 μM (4), 6.9 μM (5), 71 μM (6), 5.5 μM (7), 18 μM (8), 4.4 μM (9) and 3.6 μM (10).
1.171±0.06 g/cm3 (20°C 760 Torr)
Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc.
643.6±55.0 °C at 760 mmHg
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Alstrom Syndrome (ALMS) is an extremely rare multiorgan disease caused by mutations in ALMS1. Dilated Cardiomyopathy (DCM) is a common finding but only one series has been investigated by Cardiac Magnetic Resonance (CMR).
Eight genetically proven ALMS patients (ages 11-41) underwent CMR performed by standard cine steady state, T1, T2 and Late Gadolinium Enhancement (LGE) sequences. Ejection fraction (EF), Diastolic Volume (EDV) and Systolic Volume normalized for body surface area (ESV), and Mass indices were determined, as well as EDV/Mass ratio, an index expressing the adequacy of cardiac mass to heart volume. Regional fibrosis was assessed by LGE; diffuse fibrosis was measured by a TI scout sequence acquired at 5, 10 and 15 min after gadolinium by comparing inversion time values (TI) at null time in ALMS and control group.
In one patient severe DCM was present with diffuse LGE. There were seven cases without clinical DCM. In these patients, EF was at lower normal limits or slightly reduced and ESV index increased; six patients had decreased Mass index and EDV/Mass ratio. Mild regional non ischemic fibrosis was detected by LGE in three cases; diffuse fibrosis was observed in all cases, as demonstrated by shorter TI values in ALMS in comparison with controls (5 min:152±12 vs 186±16, p 0,0002; 10 min: 175±8 vs 204±18, p 0,0012; 15 min: 193± 9 vs 224±16, p 0,0002).
Cardiac involvement in ALMS is characterized by progressive DCM, associated with systolic dysfunction, myocardial fibrosis and reduced myocardial mass.
Alstrom Syndrome, ALMS1, Dilated cardiomyopathy, Cardiac Magnetic Resonance, fibrosis
Alstrom Syndrome: Cardiac Magnetic Resonance findings
Francesco Corbetti, MD,1 Renato Razzolini, MD, PhD,2 Vera Bettini, MD,3 Jan D Marshall, BS,4 Jurgen Naggert, PhD,4 Francesco Tona, MD, PhD,2 Gabriella Milan, BS, PhD,3 and Pietro Maffei, MD3
2014 Aug 20.
Aberrant DNA methylation is induced by aging and chronic inflammation in normal tissues. The induction by inflammation is widely recognized as acceleration of age-related methylation. However, few studies addressed target genomic regions and the responsible factors in a genome-wide manner. Here, we analyzed methylation targets by aging and inflammation, taking advantage of the potent methylation induction in human gastric mucosa by Helicobacter pylori infection-triggered inflammation.
DNA methylation microarray analysis of 482,421 CpG probes, grouped into 270,249 genomic blocks, revealed that high levels of methylation were induced in 44,461 (16.5%) genomic blocks by inflammation, even after correction of the influence of leukocyte infiltration. A total of 61.8% of the hypermethylation was acceleration of age-related methylation while 21.6% was specific to inflammation. Regions with H3K27me3 were frequently hypermethylated both by aging and inflammation. Basal methylation levels were essential for age-related hypermethylation while even regions with little basal methylation were hypermethylated by inflammation. When limited to promoter CpG islands, being a microRNA gene and high basal methylation levels strongly enhanced hypermethylation while H3K27me3 strongly enhanced inflammation-induced hypermethylation. Inflammation was capable of overriding active transcription. In young gastric mucosae, genes with high expression and frequent mutations in gastric cancers were more frequently methylated than in old ones.
Methylation by inflammation was not simple acceleration of age-related methylation. Targets of aberrant DNA methylation were different between young and old gastric mucosae, and driver genes were preferentially methylated in young gastric mucosa.
DNA methylation, Helicobacter pylori, Aging, CpG island
Distinct DNA methylation targets by aging and chronic inflammation: a pilot study using gastric mucosa infected with Helicobacter pylori
Satoshi Yamashita,#1 Sohachi Nanjo,#1,2 Emil Rehnberg,1 Naoko Iida,1 Hideyuki Takeshima,1 Takayuki Ando,2 Takao Maekita,3 Toshiro Sugiyama,2 and Toshikazu Ushijimacorresponding author1