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2.
Nat Prod Res ; 34(2): 311-316, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30404547

RESUMO

Development of a novel agent for control of schistosomiasis is a mandate. In-vitro anti-schistosomal activity of the aerial parts of Huernia saudi-arabica were examined. Chromatographic investigations of the ethanol extract (EE) were afforded three compounds. Pregnane glycoside (CI) 12-ß-p-hydroxy-benzoyl-20-O-acetyl-boucerin-3-O-ß-D-glucopyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside, in addition to two flavonoids (CII) luteolin-4'-O-ß-D-neohesperidoside and (CIII)quercetin-3-rutinoside were recognized via spectral analysis. The schistosomicidal effects were evaluated using scanning electron microscope (SEM). In-vitro bioassays on the viability (mobility, morphological changes and mortality) of Schistosoma mansoni adults, cercariae, miracidia and eggs at different concentrations 2.5, 5, 12.5, 25 and 50 µg/ml of EE and 2.6, 5.2, 13, 26 and 52 µM of CI in incubation times 1,2,4,6,12hrs were carried out. EE and CI evidenced in-vitro anti-schistosomal activity with a dose and incubation time-dependent fashion. The effect of EE and CI was evident by the topography damage showed by SEM. EE proved moderate in-vitro cytotoxicity with IC50 of 8.48 µg/ml.


Assuntos
Apocynaceae/química , Glicosídeos/farmacologia , Pregnanos/farmacologia , Esquistossomicidas/isolamento & purificação , Animais , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Glicosídeos/isolamento & purificação , Extratos Vegetais/química , Pregnanos/isolamento & purificação , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia
3.
Gen Comp Endocrinol ; 285: 113273, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31525377

RESUMO

There exists a surprising diversity in the physiology and endocrinology of pregnancy among mammals in both the source (luteal/placental) and metabolism of progesterone. To evaluate the possible diversity of steroid metabolism within toothed cetaceans, we investigated 5α-reduced progesterone metabolites and androgens in cyclic (luteal phase) and pregnant captive killer whales, belugas and bottlenose dolphins (n = 5/species) bled longitudinally in early, mid- and late pregnancy (0.16, 0.50 and 0.85 fractions of 535, 464 and 380 gestation days, respectively). Mid-luteal samples were also collected. Serum was analyzed by liquid chromatography tandem-mass spectrometry as previously validated for (among others) progesterone, 20αOH-progesterone (20αOHP), 5α-dihydroprogesterone (DHP), several additional 5α-reduced metabolites and androgens (dehydroepiandrosterone, androstenedione and testosterone). The predominant mid-luteal pregnanes were: progesterone, belugas; progesterone and 20αOHP, dolphins; allopregnanolone (3α-DHP) and progesterone, killer whales. Progesterone was 2-4-fold higher in early pregnancy than mid-luteal samples but decreased thereafter. The predominant metabolite, 3ß,20α-dihydroprogesterone (3ß,20α-DHP; 40-80 ng/ml) was higher in mid- and late-than early gestation in all 3 species. Concentrations of 20αOHP and 3ß,20α-DHP were similar at mid-gestation but 20αOHP declined in late-gestation in killer whales, and 20αOHP was lower than 3ß,20α-DHP in belugas and dolphins throughout gestation. Other 5α-reduced metabolites, DHP, 3α-DHP and 20α-DHP, were far lower throughout pregnancy (<10 ng/ml). DHP and 3α-DHP decreased from early to mid-gestation in belugas, but changed little in killer whales and dolphins. These data suggest that progesterone metabolism is relatively conserved among these cetacean species. As in equine pregnancies, 3ß,20α-DHP is the major metabolite, increasing at the expense of progesterone as pregnancy progresses. Androstenedione and testosterone also increased detectably in mid- to late-gestation in these species. The tissue source remains unknown, but progesterone metabolism during gestation in these cetaceans is similar to horses and, together with androgens, may be reliable biomarkers of pregnancy.


Assuntos
Beluga/sangue , Golfinho Nariz-de-Garrafa/sangue , Cromatografia Líquida/métodos , Esteroides/sangue , Espectrometria de Massas em Tandem/métodos , Orca/sangue , Animais , Feminino , Gravidez , Pregnanos/sangue , Progesterona/sangue , Progesterona/metabolismo
4.
N Engl J Med ; 381(10): 903-911, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31483961

RESUMO

BACKGROUND: Altered neurotransmission of γ-aminobutyric acid (GABA) has been implicated in the pathogenesis of depression. Whether SAGE-217, an oral, positive allosteric modulator of GABA type A receptors, is effective and safe for the treatment of major depressive disorder is unknown. METHODS: In this double-blind, phase 2 trial, we enrolled patients with major depression and randomly assigned them in a 1:1 ratio to receive 30 mg of SAGE-217 or placebo once daily. The primary end point was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy end points, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) (on a scale of 1 to 7, with a score of 7 indicating that symptoms are very much worse). RESULTS: A total of 89 patients underwent randomization: 45 patients were assigned to the SAGE-217 group, and 44 to the placebo group. The mean baseline HAM-D score was 25.2 in the SAGE-217 group and 25.7 in the placebo group. The least-squares mean (±SE) change in the HAM-D score from baseline to day 15 was -17.4±1.3 points in the SAGE-217 group and -10.3±1.3 points in the placebo group (least-squares mean difference in change, -7.0 points; 95% confidence interval, -10.2 to -3.9; P<0.001). The differences in secondary end points were generally in the same direction as those of the primary end point. There were no serious adverse events. The most common adverse events in the SAGE-217 group were headache, dizziness, nausea, and somnolence. CONCLUSIONS: Administration of SAGE-217 daily for 14 days resulted in a reduction in depressive symptoms at day 15. Adverse events were more common in the SAGE-217 group than in the placebo group. Further trials are needed to determine the durability and safety of SAGE-217 in major depressive disorder and to compare SAGE-217 with available treatments. (Funded by Sage Therapeutics; ClinicalTrials.gov number, NCT03000530.).


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Moduladores GABAérgicos/uso terapêutico , Pregnanos/uso terapêutico , Pirazóis/uso terapêutico , Receptores de GABA-A/metabolismo , Administração Oral , Adulto , Regulação Alostérica , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/classificação , Tontura/induzido quimicamente , Método Duplo-Cego , Feminino , Moduladores GABAérgicos/efeitos adversos , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Pregnanos/efeitos adversos , Escalas de Graduação Psiquiátrica , Pirazóis/efeitos adversos
5.
Phytochemistry ; 168: 112127, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31550672

RESUMO

Five undescribed C21 pregnane glycosides, epigycosides D-H, together with four known analogues, two lignans, and a flavonoid have been isolated from the stems of Epigynum cochinchinensis. The structures of pregnane glycosides were elucidated using spectroscopic techniques and acid hydrolysis. The in vitro immunological activities were assessed against Con A-stimulated proliferation of mice splenocytes. The C21 pregnane glycosides showed immunosuppressive activity in a concentration-dependent manner. Moreover, epigycoside E exhibited a potent immunosuppressive effect, and the IC50 value on Con A-stimulated mice splenocytes was 22.1 ±â€¯6.4 µM. Epigycoside E also caused G0/G1 arrest, and inhibited TNF-α and IL-2 production.


Assuntos
Apocynaceae/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Imunossupressores/isolamento & purificação , Imunossupressores/farmacologia , Pregnanos/isolamento & purificação , Pregnanos/farmacologia , Baço/efeitos dos fármacos , Baço/imunologia , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Concanavalina A/antagonistas & inibidores , Concanavalina A/farmacologia , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Glicosídeos/química , Imunossupressores/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Estrutura Molecular , Caules de Planta/química , Pregnanos/química , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos
6.
Nat Commun ; 10(1): 3378, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358750

RESUMO

Steroidal C19-hydroxylation is pivotal to the synthesis of naturally occurring bioactive C19-OH steroids and 19-norsteroidal pharmaceuticals. However, realizing this transformation is proved to be challenging through either chemical or biological synthesis. Herein, we report a highly efficient method to synthesize 19-OH-cortexolone in 80% efficiency at the multi-gram scale. The obtained C19-OH-cortexolone can be readily transformed to various synthetically useful intermediates including the industrially valuable 19-OH-androstenedione, which can serve as a basis for synthesis of C19-functionalized steroids as well as 19-nor steroidal drugs. Using this biocatalytic C19-hydroxylation method, the unified synthesis of six C19-hydroxylated pregnanes is achieved in just 4 to 9 steps. In addition, the structure of sclerosteroid B is revised on the basis of our synthesis.


Assuntos
Androstenodiona/química , Cortodoxona/química , Pregnanos/química , Esteroides/química , Androstenodiona/metabolismo , Biocatálise , Cortodoxona/metabolismo , Hidroxilação , Modelos Químicos , Estrutura Molecular , Pregnanos/metabolismo , Esteroides/síntese química , Esteroides/metabolismo
7.
Steroids ; 148: 28-35, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31075339

RESUMO

20R-Hydroxy short-chain ecdysteroids were synthesized by chemo- and stereoselective reduction of poststerone acetonide with L-Selectride or LiAlH4. The same reaction with the excess of L- Selectride followed by the treatment of the reaction mixture with hydrochloric acid is accompanied by (8R)-13(14 → 8)abeo- rearrangements, which resulted in the contraction/expansion of C/D pregnane rings. The reaction of 20R-hydroxy poststerone analogs with (diethylamino)sulfur trifluoride (DAST) proceeds through intramolecular rearrangements and provides D-homo- or 13,14-seco- androstane structures.


Assuntos
Androstanos/síntese química , Ecdisterona/química , Pregnanos/síntese química , Esteroides/química , Androstanos/química , Conformação Molecular , Pregnanos/química , Teoria Quântica , Estereoisomerismo , Termodinâmica
8.
Chem Biodivers ; 16(6): e1900062, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30983116

RESUMO

Seven new polyhydroxypregnane glycosides, named cynotophyllosides P-V, together with three known analogs were isolated from the roots of Cynanchum otophyllum C.K.Schneid. Their structures were elucidated by a variety of spectroscopic techniques, as well as acid-catalyzed hydrolysis. All isolates were tested for their immunological activities in vitro against Con A- and LPS-induced proliferation of mice splenocytes. Immunoenhancing (for 1, 9) and immunosuppressive (for 2) activities were observed. Furthermore, cynotophylloside R (3) showed immunomodulatory as it enhanced the proliferation of splenocytes in low concentration and suppressed immune cells in concentration more than 1.0 µg/ml.


Assuntos
Cynanchum/química , Glicosídeos/química , Pregnanos/química , Animais , Proliferação de Células/efeitos dos fármacos , Cynanchum/metabolismo , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Conformação Molecular , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Baço/citologia , Baço/efeitos dos fármacos , Baço/metabolismo
9.
Rinsho Shinkeigaku ; 59(4): 177-184, 2019 Apr 25.
Artigo em Japonês | MEDLINE | ID: mdl-30930364

RESUMO

Levodopa-carbidopa intestinal gel (LCIG) therapy has been established as a device-aided treatment for advanced Parkinson's disease. We retrospectively investigated the issues related to LCIG therapy in patients with Parkinson's disease at our hospital from March 2014 to July 2018. The subjects were 18 patients including nine men and nine women. The mean duration of PD symptoms and motor fluctuation was 14.5 ± 5.9 and 7.2 ± 4.5 years, respectively. The mean age at initiation of LCIG was 60.1 ± 9.4 years and the mean treatment period was 21.1 ± 19.5 months. One hundred and sixteen LCIG-associated issues were observed, including pain at the gastrostomy site (23 cases), hypergranulation tissue (14 cases), skin redness and/or erosions (11 cases), cutaneous infections at the gastrostomy site (eight cases), percutaneous endoscopic gastrojejunostomy (PEG-J) tube occlusion in the gastrointestinal tract (19 cases), irremovable PEG-J tube (13 cases), dislocation of the PEG-J tube (six cases), and breakage of the connector (eight cases). The majority of these issues were easily diagnosed and could be managed by neurologists who are familiar with LCIG therapy.


Assuntos
Antiparkinsonianos/administração & dosagem , Carbidopa/administração & dosagem , Gastrostomia/efeitos adversos , Gastrostomia/instrumentação , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Idoso , Combinação de Medicamentos , Feminino , Derivação Gástrica/efeitos adversos , Derivação Gástrica/instrumentação , Géis , Glicosídeos , Humanos , Bombas de Infusão/efeitos adversos , Intubação/efeitos adversos , Intubação/instrumentação , Masculino , Pessoa de Meia-Idade , Pregnanos , Estudos Retrospectivos , Dermatopatias Infecciosas/etiologia
10.
Surg Today ; 49(10): 828-835, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30968225

RESUMO

PURPOSE: We compared three-dimensional (3D) and two-dimensional (2D) measurements of the solid component to determine radiological criteria for sublobar resection of lung adenocarcinoma ≤ 2 cm in size. METHODS: We included 233 surgical cases. The maximum size of the solid component for 3D measurement was calculated by delineating the solid component on successive axial images and reconstructing the 3D surface model. RESULTS: The predictive performance for adenocarcinoma in situ (n = 43) and minimally invasive adenocarcinoma (n = 77) were equivalent to areas under the curve of 0.871 and 0.857 for 2D and 3D measurements (p = 0.229), respectively. A solid component of 5 mm had a prognostic impact on both measurements ( ≤ 5 mm versus > 5 mm; p = 0.003 for 2D and p = 0.002 for 3D, log-rank test). Survival rates at 5 years were 94.7-96.9% following lobectomy and sublobar resection among patients with a solid component ≤ 5 mm in size. Sublobar resection resulted in worse survival rates, with declines at 5 years of 15.8% on 2D and 11.5% on 3D measurements, than lobectomy in patients with a solid component > 5 mm in size. CONCLUSIONS: A solid component ≤ 5 mm in size is an appropriate criterion for sublobar resection for both measurements. In addition, 2D measurement is justified because of its simple implementation.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Imageamento Tridimensional , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Tomografia Computadorizada por Raios X , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glicosídeos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/mortalidade , Pregnanos , Taxa de Sobrevida
11.
J Enzyme Inhib Med Chem ; 34(1): 684-691, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30777494

RESUMO

Synthetic progesterone and 5α/ß-pregnane-3,20-dione derivatives were evaluated as in vitro and in vivo modulators of multidrug-resistance (MDR) using two P-gp-expressing human cell lines, the non-steroidogenic K562/R7 erythroleukaemia cells and the steroidogenic NCI-H295R adrenocortical carcinoma cells, both resistant to doxorubicin. The maximal effect in both cell lines was observed for 7α-O-benzoyloxy,11α(R)-O-tetrahydropyranyloxy-5ß-pregnane-3,20-dione 4. This modulator co-injected with doxorubicin significantly decreased the tumour size and increased the survival time of immunodeficient mice xenografted with NCI-H295R or K562/R7 cells.


Assuntos
Antineoplásicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Pregnanos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos SCID , Conformação Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Pregnanos/síntese química , Pregnanos/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
12.
Reproduction ; 157(5): 413-422, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30763279

RESUMO

Dexamethasone (DEX) initiates parturition by inducing progesterone withdrawal and affecting placental steroidogenesis, but the effects of DEX in fetal and maternal tissue steroid synthetic capacity remains poorly investigated. Blood was collected from cows at 270 days of gestation before DEX or saline (SAL) treatment, and blood and tissues were collected at slaughter 38 h later. Steroid concentrations were determined by liquid chromatography tandem mass spectrometry to detect multiple steroids including 5α-reduced pregnane metabolites of progesterone. The activities of 3ß-hydroxysteroid dehydrogenase (3ßHSD) in cotyledonary and luteal microsomes and mitochondria and cotyledonary microsomal 5α-reductase were assessed. Quantitative PCR was used to further assess transcripts encoding enzymes and factors supporting steroidogenesis in cotyledonary and luteal tissues. Serum progesterone, pregnenolone, 5α-dihydroprogesterone (DHP) and allopregnanolone (3αDHP) concentrations (all <5 ng/mL before treatment) decreased in cows after DEX. However, the 20α-hydroxylated metabolite of DHP, 20αDHP, was higher before treatment (≈100 ng/mL) than at slaughter but not affected by DEX. Serum, cotyledonary and luteal progesterone was lower in DEX- than SAL-treated cows. Progesterone was >100-fold higher in luteal than cotyledonary tissues, and serum and luteal concentrations were highly correlated in DEX-treated cows. 3ßHSD activity was >5-fold higher in luteal than cotyledonary tissue, microsomes had more 3ßHSD than mitochondria in luteal tissue but equal in cotyledonary sub-cellular fractions. DEX did not affect either luteal or cotyledonary 3ßHSD activity but luteal steroidogenic enzyme transcripts were lower in DEX-treated cows. DEX induced functional luteal regression and progesterone withdrawal before any changes in placental pregnene/pregnane synthesis and/or metabolism were detectable.


Assuntos
Bovinos , Dexametasona/farmacologia , Parto/efeitos dos fármacos , Prenhez , Pregnanos/metabolismo , Pregnenos/metabolismo , Animais , Bovinos/metabolismo , Corpo Lúteo/efeitos dos fármacos , Corpo Lúteo/metabolismo , Feminino , Feto/efeitos dos fármacos , Feto/metabolismo , Idade Gestacional , Luteólise/sangue , Luteólise/efeitos dos fármacos , Luteólise/metabolismo , Parto/metabolismo , Gravidez , Prenhez/sangue , Prenhez/efeitos dos fármacos , Prenhez/metabolismo , Pregnanos/sangue , Pregnenos/sangue , Progesterona/metabolismo
13.
J Nat Med ; 73(1): 93-103, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30251034

RESUMO

Seven new pregnane glycosides (1-7) and eight known compounds (8-15) were isolated from the bark of Marsdenia cundurango (Asclepiadaceae). The structures of 1-7 were determined by spectroscopic analysis, including two-dimension NMR spectroscopy, chemical transformations, and chromatographic analysis of the hydrolyzed products. The isolated compounds 1-15 were evaluated for their cytotoxic activity against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, and TIG-3 normal human lung cells, including apoptosis-inducing activity of a representative pregnane glycoside in HL-60 cells.


Assuntos
Citotoxinas/uso terapêutico , Glicosídeos/química , Células HL-60/metabolismo , Marsdenia/química , Casca de Planta/química , Pregnanos/química , Citotoxinas/farmacologia , Humanos
14.
Nat Prod Res ; 33(11): 1570-1576, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29334245

RESUMO

A new polyhydroxylated pregnane, named lß,2ß,3ß,4ß,5ß,6ß-hexolhydroxy-pregn-16-en-20-one (1), along with nine known (2-10) steroidal saponins were isolated from the whole plant of Reineckia carnea. Structure elucidations of all compounds were established by interpretation of their NMR spectral data, HR-ESI-MS and comparing with literatures. In addition, these compounds were evaluated with anticomplement activity. The result showed that compound 1 exhibited anticomplement effects with the CH50 values of 0.043 mg/mL, but saponins (2-10) showed no inhibition. Interestingly, hydrolysis of steroidal saponins (2-10) resulted in its aglycones (2a-10a) correspondingly which showed anticomplement activity with the CH50 values of 0.049-0.156 mg/mL.


Assuntos
Asparagaceae/química , Inativadores do Complemento/farmacologia , Esteroides/química , Esteroides/farmacologia , Animais , Inativadores do Complemento/química , Avaliação Pré-Clínica de Medicamentos/métodos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Cobaias , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pregnanos/química , Pregnanos/farmacologia , Saponinas/química , Saponinas/farmacologia , Ovinos , Espectrometria de Massas por Ionização por Electrospray
15.
Nat Prod Res ; 33(22): 3210-3214, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29726713

RESUMO

Phytochemical investigation on the ethyl acetate fraction of the leaves of Epigynum cochinchinensis led to the isolation of a new C21 pregnane glycoside, epigycoside B (1), together with three known analogues. Their structures were elucidated on the basis of extensive spectroscopic techniques, including UV, MS, and NMR experiments, as well as the chemical methods. Compound 1 displayed in vitro immunosuppressive activity against concanavalin A (Con A)/Lipopolysaccharides (LPS)-stimulated proliferation of mice splenocyte. The activity was significant as compared with control group at 50 µM concentration.


Assuntos
Apocynaceae/química , Glicosídeos/farmacologia , Imunossupressores/isolamento & purificação , Pregnanos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Concanavalina A/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/imunologia , Glicosídeos/isolamento & purificação , Imunossupressores/química , Imunossupressores/farmacologia , Lipopolissacarídeos , Camundongos , Estrutura Molecular , Folhas de Planta/química , Pregnanos/química , Pregnanos/imunologia , Pregnanos/isolamento & purificação , Análise Espectral , Baço/citologia
16.
Nat Prod Res ; 33(13): 1885-1890, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29865893

RESUMO

A new pregnane steroid, named aspergillon A (1), together with two known compounds, (22E,24R)-ergosta-5,7,22-trien-3ß-ol (2) and (22E, 24R)-ergosta-4,6,8(14),22-tetraen-3-one (3) were isolated from cultures of the tin mine tailings-associated fungus Aspergillus versicolor. The new structure and absolute configuration were determined with the help of extensive spectroscopic analyses and quantum chemical calculations of the electronic circular dichroism (ECD) spectra.


Assuntos
Aspergillus/química , Pregnanos/isolamento & purificação , Esteroides/isolamento & purificação , Dicroísmo Circular , Fungos , Mineração , Estrutura Molecular , Pregnanos/química , Análise Espectral , Esteroides/química
17.
Theriogenology ; 122: 130-136, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30265893

RESUMO

The objectives of this study were to compare via liquid chromatography-tandem mass spectrometry (LC-MS/MS) progesterone (P4), 5α-dihydroprogesterone (DHP), allopregnanolone, 3ß-hydroxy-5α-pregnan-20-one (3ß5P), 20α-hydroxy-5α-pregnan-3-one (20α5P), 5α-pregnan-3ß,20α-diol (ßα-diol), and 5α-pregnan-3ß,20ß-diol (ßß-diol) concentrations in plasma of mares with experimentally-induced, ascending placentitis compared to gestationally age-matched control mares. Placentitis was induced via intracervical inoculation of Streptococcus equi spp. zooepidemicus between 260 and 280 days of gestation. Placentitis mares were subdivided into those which aborted in less than eight days (n = 6; acute) and those that aborted at ≥ 8 days after inoculation (n = 9; chronic). Ten pregnant mares at similar gestational ages served as healthy controls. Pregnanes were measured for days (-8), -6, -4, -3, -2, -1, and 0 days preceding abortion in the treated mares, and for the matched days of gestation in the control mares by LC-MS/MS and by immunoassay for immunoreactive (ir) P4. In mares with chronic placentitis, concentrations of DHP and its downstream metabolites (allopregnanolone, 3ß5P, 20α5P, ßα-diol) increased at 2-8 days prior to abortion compared to control mares. Of these pregnanes, 20α5P and ßα-diol increased at eight days prior to abortion and demonstrated the largest increase (approximately 3 to 4×) in mares with chronic placentitis compared to control mares. Concentrations of P4 determined by LC-MS/MS were at or below the limit of detection (0.5 ng/mL) for control mares and did not increase significantly in mares with chronic placentitis. Immunoreactive-P4 was increased at two days prior to abortion in mares with chronic placentitis but was not different from controls in mares with acute placentitis. In mares with acute placentitis, concentrations of DHP, allopregnanolone, 3ß5P, 20α5P, and ßα-diol decreased within 0-3 days prior to abortion. In mares with chronic placentitis, the patterns of increased pregnanes metabolized by the placenta was similar to changes in maternal pregnanes noted in normal mares beyond Day 300 of gestation and likely represent the effects of fetal stress and adrenal activation on pregnane metabolism by the fetus and placenta. Decreases in these same pregnanes in mares with acute cases likely reflect extreme fetal or placental compromise.


Assuntos
Doenças dos Cavalos/metabolismo , Doenças Placentárias/veterinária , Pregnanos/sangue , Animais , Cromatografia Líquida/veterinária , Feminino , Doenças dos Cavalos/microbiologia , Cavalos , Doenças Placentárias/metabolismo , Doenças Placentárias/microbiologia , Gravidez , Pregnanos/química , Streptococcus equi , Espectrometria de Massas em Tandem/veterinária
18.
Am J Primatol ; 80(11): e22917, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30221787

RESUMO

The wild population of spectral tarsier is declining and attempts to breed the species in captivity have been of limited success. One possible reason for this is that information on the reproductive biology of Tarsius tarsier is extremely limited and data on the species reproductive physiology are completely lacking. We validated fecal estrogen (E-total) and progesterone metabolite (5-P-3OH) measurements for monitoring female ovarian activity and pregnancy. We used this approach to provide the first data on cycle and pregnancy length based on endocrine information in this species. We collected regular fecal samples in combination with observations on socio-sexual behaviors for a maximum of 15 months from three females maintained at Primate Research Center of Bogor Agricultural University, Indonesia. Hormonal profiles indicated that behavioral estrus was associated with marked elevations in fecal E-total concentrations followed by increases in 5-P-3OH levels indicating luteal function. Pregnancy was characterized by low levels of E-total and 5-P-3OH during the first month and markedly rising concentrations thereafter. An ovarian cycle length of 21.7 ± 5.7 days was found. Gestation length was 128d (live infant), 131d (stillbirth), and 164d (death of mother and infant due to dystocia). Despite the small sample size, the study demonstrates the overall validity of fecal sex hormone metabolite measurements for reproductive monitoring in female T. tarsier, as such, the methods described here may ultimately help to improve the breeding management of the species in captivity. They may also offer new opportunities for investigating basic questions of tarsier reproductive biology in the wild by using fecal hormone metabolite analysis to diagnose pregnant animals and determine reproductive rates in relation to ecological and other factors influencing tarsier reproduction. Thus, non-invasive assessment of female reproductive condition as described here may ultimately contribute to facilitate in and ex situ conservation efforts of this endangered primate species.


Assuntos
Ciclo Menstrual/fisiologia , Gravidez/fisiologia , Comportamento Sexual Animal/fisiologia , Tarsiidae/fisiologia , Animais , Distocia/mortalidade , Distocia/veterinária , Estrogênios/análise , Fezes/química , Feminino , Pregnanos/análise , Natimorto/veterinária , Tarsiidae/metabolismo
19.
J Agric Food Chem ; 66(29): 7735-7739, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-29965760

RESUMO

To investigate the sweet-tasting components in the roots of Myriopteron extensum, the phytochemical study of its roots was conducted, which led to the discovery of 12 new C21 pregnane glycosides (extensumside M-X, 1-12) and two known ones (extensumside C and extensumside E, 13-14). Their chemical structure elucidation was accomplished by means of spectroscopic methods: IR, UV, ESI-MS, and NMR (1H NMR, 13C NMR, HSQC, 1H-1H COSY, HMBC, HSQC-TOCSY, and ROESY), as well as the chemical evidence. Sensory analysis of these compounds revealed that nine of them (1, 3, 4, 5, 6, 7, 8, 13, and 14) are highly sweet-tasting compounds. Their sweetness intensities are 25 to 400 times greater than that of sucrose. Analysis of the structure-activity relationship (SAR) indicated that the sweet intensities of the isolated compounds are closely related to the aglycone 3ß,16α-dihydroxy-pregn-5-en-20-one, the number and type of the monosaccharide in the sugar chain linked to C-3 and C-16 and the position of the mBe group.


Assuntos
Apocynaceae/química , Glicosídeos/química , Extratos Vegetais/química , Pregnanos/química , Edulcorantes/química , Glicosídeos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Pregnanos/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray , Edulcorantes/isolamento & purificação , Paladar
20.
Asian Pac J Cancer Prev ; 19(6): 1457-1464, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29936715

RESUMO

Objective: This study aims to isolate the active anticancer compound from ethyl acetate fraction extracted from the roots of Calotropis gigantea and to determine the operating mechanism of the isolates towards WiDr colon cancer cells. Methods: the isolation was conducted by using bioassay guided isolation approach method. The cytotoxic potential was determined by using MTT method. The chemical structure was identified by using UPLCMS/MS and NMR-1H spectroscopy. The cell cycle arrest and apoptosis induction were determined by flow cytometry method. The expression of caspase-8 was determined by immunocytochemistry method. Results: The results showed that the active compounds are obtained calotroposid A compound which is glycosides terpenoids. Calotroposide A is capable of inhibiting the growth of WiDr colon cancer cells at IC50 17.23µg/ml. Cell apoptosis induction took place and was indicated by cell apoptosis increase, S and G2/M accumulation and by caspase-8 expression. Conclusion: Calotroposide A induces anticancer activity against WiDr colon cancer cells by means of apoptosis induction mechanism through extrinsic pathway with increased expression of caspase-8.


Assuntos
Apoptose/efeitos dos fármacos , Calotropis/química , Caspase 8/metabolismo , Neoplasias do Colo/patologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pregnanos/farmacologia , Saponinas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células Tumorais Cultivadas
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