RESUMEN
Aurones constitute one of the major classes of flavonoids, with a characteristic furanone structure that acts as the C-ring of flavonoids. Members of various enzyme families are involved in aurone biosynthesis in different higher plants, suggesting that during evolution plants acquired the ability to biosynthesize aurones independently and convergently. Bryophytes also produce aurones, but the biosynthetic pathways and enzymes involved have not been determined. The present study describes the identification and characterization of a polyphenol oxidase (PPO) that acts as an aureusidin synthase (MpAS1) in the model liverwort, Marchantia polymorpha. Crude enzyme assays using an M. polymorpha line overexpressing MpMYB14 with high accumulation of aureusidin showed that aureusidin was biosynthesized from naringenin chalcone and converted to riccionidin A. This activity was inhibited by N-phenylthiourea, an inhibitor specific to enzymes of the PPO family. Of the six PPOs highly induced in the line overexpressing MpMyb14, one, MpAS1, was found to biosynthesize aureusidin from naringenin chalcone when expressed in Saccharomyces cerevisiae. MpAS1 also recognized eriodictyol chalcone, isoliquiritigenin and butein, showing the highest activity for eriodictyol chalcone. Members of the PPO family in M. polymorpha evolved independently from PPOs in higher plants, indicating that aureusidin synthases evolved in parallel in land plants.
Asunto(s)
Chalconas , Marchantia , Catecol Oxidasa/genética , Catecol Oxidasa/química , Catecol Oxidasa/metabolismo , Marchantia/genética , Marchantia/metabolismo , FlavonoidesRESUMEN
Comparative studies of the potency of long- and short-acting erythropoiesis-stimulating agents (L-ESAs and S-ESAs) on erythropoietic activity in patients with chronic kidney disease without dialysis have not been performed, although L-ESAs are used in many countries. We performed a retrospective analysis of non-dialysis (ND) patients who had received L-ESA or S-ESA. More days were needed for the S-ESA-treated group (368 d) to reach the haemoglobin (Hb) reference range than for the L-ESA-treated group (126 d). Therefore, we investigated risk factors that influence the period until the Hb level reaches the reference range. Patients were classified into two groups by the period until the Hb level was stabilised within the reference range: the short- and long-term group. Two risk factors for delayed Hb stabilisation were identified: age ≥60 years; and administration of an S-ESA for initial treatment. These findings suggest that the Hb level should be carefully monitored during ESA therapy in elderly ND patients, and that the ESA dose should be increased or L-ESA therapy should be utilised to treat renal anaemia.
Asunto(s)
Anemia/prevención & control , Eritropoyesis/efectos de los fármacos , Eritropoyetina/sangre , Hematínicos/uso terapéutico , Hemoglobinas/metabolismo , Insuficiencia Renal Crónica/complicaciones , Factores de Edad , Anciano , Anciano de 80 o más Años , Anemia/sangre , Femenino , Hematínicos/farmacología , Humanos , Inmunoterapia Adoptiva , Masculino , Persona de Mediana Edad , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Estudios Retrospectivos , Factores de TiempoRESUMEN
From the heartwood of Dalbergia parviflora, eight new compounds, khrinones A (1), B (2), C (3), D (4), and E (5), isodarparvinol B (6), dalparvin (7), and (3S)-sativanone (22), along with 32 known compounds, have been isolated and characterized as 17 isoflavones, nine isoflavanones, five flavanones, six isoflavans, and three miscellaneous substances. Isolates were evaluated for their cell proliferation stimulatory activity against the MCF-7 and T47D human breast cancer cell lines, and their luciferase inductive effects using luciferase transiently transfected MCF-7/luc and T47D/luc cells were also determined. Isoflavones such as genistein (10), biochanin A (11), tectorigenin (12), and 2'-methoxyformononetin (13) stimulated the proliferation of both cells, and concentrations of lower than 1 muM of these compounds showed equivalent activity to 10 pM of estradiol (E2). The new isoflavanone (22) also showed activity against both cell types, although it was weaker than that of the corresponding isoflavone (2'-methoxyformononetin, 13). Two optically active isoflavanones (22 and 24: (3S)-violanone) stimulated the proliferation of both cell lines at lower concentrations than three racemates (21: vestitone, 23: 7,3'-dihydroxy-4'-methoxyisoflavanone, and 25: 3-O-methylviolanone). Bowdichione (20), an isoflavone with a quinone structure in its B-ring, showed activity against only one cell line associated with MCF-7 in these assays.
Asunto(s)
Dalbergia/química , Estrógenos/aislamiento & purificación , Estrógenos/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Plantas Medicinales/química , Ensayos de Selección de Medicamentos Antitumorales , Estrógenos/química , Femenino , Flavonoides/química , Humanos , Luciferasas/efectos de los fármacos , Estructura Molecular , Estereoisomerismo , Tailandia , Madera/químicaRESUMEN
From the heartwood of Dalbergia parviflora, five compounds, dalparvin A (1), B (2), C (3), dalparvinol C (4), and neokhriol A (5), along with 11 known compounds, kenusanone G (6), cajanin (7), sophorol (8), alpinetin (9), hesperetin (10), 3'-O-methylorobol, odoratin, (2R)(3R)-2,3-trans 7-hydroxy-5-methoxydihydroflavonol, (6aR, 11aR)-3,8-dihydroxy-9-methoxypterocarpan, (6aR, 11aR)- vesticarpan, and methyl-3,4-dihydroxy-2-methoxybenzoate were isolated and characterized. Isolates were evaluated for their cell proliferation stimulatory activity against MCF-7, T-47D, and BT20 human breast cancer cell lines. Along with 7-10, two compounds 2 and 3 stimulated not only MCF-7, but also T-47D human breast cancer cell proliferation. Compound 6 had activity only against MCF-7 cells, and the activity of 7 was more than equivalent to that of daidzein. On the other hand, none of the isolates had any significant effects on BT20 cell proliferation, and these results indicated that the stimulative activity of these compounds was not general to any cell proliferations. Furthermore, these compounds were tested in the estrogen-responsive transient luciferase reporter assay.