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1.
Medicine (Baltimore) ; 98(35): e16589, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464893

RESUMO

RATIONALE: Lipid deposition on the cornea without previous infection, inflammation, vascularization, or trauma is idiopathic lipid keratopathy. In vivo laser confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) are 2 noninvasive methods that can help identify the structures and morphological characteristics of the focus. PATIENT CONCERNS: A 63-year-old woman with ipsilateral corneal lipid deposits developing from a small white spot into a yellow-white superotemporal elliptic shape within a year. AS-OCT showed peripheral deep stromal deposits. IVCM showed hyper-reflective material with typical crystalline-like or needle-like structures in the superotemporal area. DIAGNOSIS: Idiopathic lipid degeneration. INTERVENTIONS: Topical steroids eye drops 3 times a day for a month and further consultation every 3 months. OUTCOMES: This patient of idiopathic lipid keratopathy was observed every 3 months and till now we have reviewed this patient twice. Topical steroids eye drops were only used during the first month. No further development was observed about the lesion and the patient's visual acuity remained good. CONCLUSION: IVCM and AS-OCT can help identify the characteristic crystalline-like or needle-like hyper-reflective material that could help diagnosis of idiopathic lipid degeneration.


Assuntos
Córnea/diagnóstico por imagem , Doenças da Córnea/tratamento farmacológico , Metabolismo dos Lipídeos , Esteroides/administração & dosagem , Administração Tópica , Córnea/metabolismo , Doenças da Córnea/diagnóstico por imagem , Doenças da Córnea/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Microscopia Confocal , Pessoa de Meia-Idade , Esteroides/farmacologia , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
2.
Medicine (Baltimore) ; 98(35): e16924, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464928

RESUMO

Autoimmune hepatitis (AIH) is a disorder of unknown etiology in which immune-mediated liver damage progresses to cirrhosis or hepatocellular carcinoma (HCC). The mainstay therapy for AIH is steroids and other immunosuppressive treatments. Currently, there are no validated markers for monitoring immune-mediated hepatic inflammation. Galectin-9 has recently been identified as a potential biomarker in patients with chronic liver disease. The objective of this study was to determine whether Galectin-9 and other serum proteins are associated with active disease in AIH patients.We enrolled 77 Japanese patients with well-documented AIH who were identified from the National Hospital Organization-AIH-liver-network database, as well as 32 patients with chronic hepatitis C (CHC), 27 patients with SLE, and 17 healthy control subjects. Serum levels of galectin-9, and markers of liver injury were measured and compared between groups.Serum levels of galectin-9 were significantly higher in AIH patients than in CHC patients (13.8 ±â€Š4.9 ng/mL vs 8.9 ±â€Š3.0 ng/mL, P < .001) or healthy controls (13.8 ±â€Š4.9 ng/mL vs 5.0 ±â€Š1.3 ng/mL, P < .001). In AIH group, serum galectin-9 levels weakly correlated with alanine aminotransferase levels or total bilirubin (TB) and strongly correlated with C-X-C motif chemokine 10 (CXCL10) and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, but did not correlate with the histological grade of liver fibrosis. Steroid treatment of AIH patients significantly reduced serum galectin-9 levels (14.1 ±â€Š4.9 ng/mL vs 8.3 ±â€Š3.8 ng/mL, P < .001). SLE patients exhibited higher galectin-9 levels, whereas the galectin-9 levels did not correlate with liver function tests such as alanine aminotransferase levels.Serum galectin-9 correlated with disease status in AIH patients and could thus be useful biomarkers to detect hepatic autoimmunity. Because circulating galectin-9 reflects autoimmune-mediated inflammation, it may have additional utility as a biomarker for other autoimmune disorders.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Biomarcadores/sangue , Proteínas de Transporte/sangue , Galectinas/sangue , Glicoproteínas/sangue , Hepatite Autoimune/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Hepatite C Crônica/sangue , Hepatite C Crônica/metabolismo , Hepatite Autoimune/sangue , Humanos , Japão , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Esteroides/administração & dosagem , Esteroides/farmacologia , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
3.
Eur J Med Chem ; 179: 694-706, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284080

RESUMO

Unique derivatives of androstene and estrane series containing N-sulfonylimidate pendants were prepared from 17α-ethynyl steroids via Cu-catalyzed azide-alkyne cycloaddition to tosyl azide in the presence of alcohols. The synthesized compounds were screened for cytotoxicity against human breast cancer cell lines and ERα agonist activity. The hit compound 3,17ß-dimethoxy-17α-[iso-propyl-2'-N-tosylacetimidate]estra-1,3,5(10)-triene (4n) had no ERα-mediated hormonal activity and was found to exhibit potent cytotoxic effect in an ERα-positive breast cancer cell line. N-Sulfonylimidate 4n displayed high antiproliferative potency against triple-negative MDA-MB-231 breast cancer cells, while it was non-toxic towards normal mammary epithelial cells. Compound 4n was found to alter activity of various signaling pathways (NF-κB, Slug, cyclin D1, ERK) supporting the growth and invasiveness of tumor cells.


Assuntos
Antineoplásicos/farmacologia , Imidoésteres/farmacologia , Esteroides/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imidoésteres/síntese química , Imidoésteres/química , Células MCF-7 , Estrutura Molecular , Esteroides/síntese química , Esteroides/química , Relação Estrutura-Atividade , Neoplasias de Mama Triplo Negativas/patologia
4.
Fitoterapia ; 137: 104268, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306720

RESUMO

Solanum nigrum L. (also called as European black nightshade) has been traditionally used as folk medicine and food in some regions. Phytochemical investigations of the immature fruits of S. nigrum yielded five steroidal alkaloid glycosides (1-5), including an unprecedented nor-spirosolane type steroidal alkaloid with a five-membered ring A (1) and two novel spirosolane type steroidal alkaloid glycosides (2, 3), together with eight known phenolic compounds (6-13). Their structures were elucidated on the basis of spectroscopic and chemical methods, including IR, NMR, HR-ESI-MS, and GC analyses. Five steroidal alkaloid glycosides were tested for their potential antiproliferative effects against HL-60, U-937, Jurkat, K562, and HepG2 cell lines and inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in a macrophage cell line RAW 264.7. Compound 1 exhibited significant inhibition on NO production with an IC50 value of 23.4 ±â€¯2.0 µM, compared to positive control indomethacin (IC50, 47.40 ±â€¯4.50 µM). Compound 4 exhibited significant cytotoxicity against all tested cell lines.


Assuntos
Alcaloides/farmacologia , Glicosídeos/farmacologia , Solanum nigrum/química , Esteroides/farmacologia , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , China , Frutas/química , Glicosídeos/isolamento & purificação , Humanos , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Células RAW 264.7 , Esteroides/isolamento & purificação
5.
Eur J Med Chem ; 178: 168-176, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31181481

RESUMO

The androgen receptor (AR) is a steroid hormone receptor and its high expression and disruption of its regulation are strongly implicated in prostate cancer (PCa) development. One of the current therapies includes application of steroidal antiandrogens leading to blockade of the AR action by the abrogation of AR-mediated signaling. We introduced here novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused steroidal compounds, described their synthesis based on [8π+2π] cycloaddition reactions of diazafulvenium methides with different steroidal scaffolds and showed their biological evaluation in different prostate cancer cell lines in vitro. Our results showed the ability of novel compounds to suppress the expression of known androgen receptor targets, Nkx3.1 and PSA in two prostate cell lines, 22Rv1 and VCaP. Candidate compound diminished the transcription of AR-regulated genes in the reporter cell line in a concentration-dependent manner. Antiproliferative activity of the most promising steroid was studied by clonogenic assay and induction of apoptosis in treated cells was documented by immunoblot detection of cleaved PARP.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Pirazóis/farmacologia , Piridinas/farmacologia , Esteroides/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Simulação de Acoplamento Molecular , Pirazóis/síntese química , Pirazóis/metabolismo , Piridinas/síntese química , Piridinas/metabolismo , Receptores Androgênicos/metabolismo , Esteroides/síntese química , Esteroides/metabolismo , Fatores de Transcrição/metabolismo
6.
Sheng Li Xue Bao ; 71(3): 463-470, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31218337

RESUMO

Anabolic-androgenic steroid (AAS) is responsible for muscle building and masculinizing. Using AAS can enhance muscle development and strength, and improve athletic performance. AAS abuse is not only seen in sport. Research has shown that there is an increasing number of adolescent AAS abusers. Adolescents are at a critical period of physical and mental development. Sex hormones are one of the important physiological factors affecting the development of their bodies and brains. Long-term or high-dose AAS treatment is likely to cause irreversible damage to their nervous system and psychological behavior, and these effects are easily overlooked. The article reviewed the long-term adverse effects of AAS on psychological behavior, emotion, cognitive functions and the nervous system of adolescents.


Assuntos
Anabolizantes/farmacologia , Cognição/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Esteroides/farmacologia , Adolescente , Humanos , Transtornos Relacionados ao Uso de Substâncias
7.
Planta Med ; 85(9-10): 755-765, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31185503

RESUMO

Antcin-A (ATA) is a steroid-like phytochemical isolated from the fruiting bodies of a precious edible mushroom Antrodia cinnamomea. We previously showed that ATA has strong anti-inflammatory and anti-tumor effects; however, other possible bioactivities of this unique compound remain unexplored. In the present study, we aimed to investigate the modulation of epithelial-to-mesenchymal transition (EMT), anti-migration, and anti-invasive potential of ATA against human breast cancer cells in vitro. Human breast cancer cell lines, MCF-7 and MDA-MB-231, were incubated with ATA for 24 h. Wound healing, trans-well invasion, western blot, q-PCR, F-actin staining, and immunofluorescence assays were performed. We found that treatment with ATA significantly blocked EMT processes, as evidenced by upregulation of epithelial markers (E-cadherin and occludin) and downregulation of mesenchymal markers (N-cadherin and vimentin) via suppression of their transcriptional repressor ZEB1. Next, we found that ATA could induce miR-200c, which is a known player of ZEB1 repression. Further investigations revealed that ATA-mediated induction of miR-200c is associated with transcriptional activation of p53, as confirmed by the fact that ATA failed to induce miR-200c or suppress ZEB1 activity in p53 inhibited cells. Further in vitro wound healing and trans-well invasion assays support that ATA could inhibit migratory and invasive potentials of breast cancer cells, and the effect was likely associated with induced phenotypic modulation. Taken together, the present study suggests that antcin-A could be a lead phyto-agent for the development of anti-metastatic drug for breast cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Esteroides/farmacologia , Proteína Supressora de Tumor p53/genética , Antígenos CD/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , MicroRNAs/genética , Fator de Crescimento Transformador beta1/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
8.
Phytochemistry ; 164: 172-183, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158602

RESUMO

Screening assays showed that total glycoside-rich fraction (TG) of rhizomes of Polygonatum sibiricum unveiled remarkable anti-proliferative activities against three cancer cell lines (A549, HepG2, and Caco2). Activity-guided isolation of TG afforded seven undescribed steroidal glycosides (polygonosides 1-7), along with 24 known glycosides. Their structures were established by 1D and 2D NMR spectroscopic analyses, high-resolution mass spectrometry, and chemical evidence. The isolated steroidal glycosides were tested for their antiproliferative activities against A549, HepG2, and Caco2 cells. Compounds 8, 10, 11, and 16 possessed stronger anticancer activities against A549 cells than the positive control Bay (25.8 µM), with IC50 values ranging from 5.8 to 24.2 µM. Compound 10 reduced the expression of Blc-2 and pro-caspase3 and increased the production of Bax as determined by western blotting. Molecular docking experiment suggested that 10 bound stably to the BH3-binding groove of the Bcl-2 protein by hydrogen bond interactions. These compounds could be candidates for anticancer agents with cytotoxic activity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Glicosídeos/farmacologia , Polygonatum/química , Rizoma/química , Esteroides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-Atividade
9.
J Appl Microbiol ; 127(1): 109-120, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31067345

RESUMO

AIMS: To determine how the microbicide ceragenin-13 (CSA-13) kills Bacillus subtilis spores prepared on growth or sporulation media, and these spores' properties. METHODS AND RESULTS: Spores made on Luria broth (LB) growth or double-strength Schaeffer's-glucose (2xSG) sporulation plates found that spores made on LB plates have coat defects as evidenced by their lower hypochlorite resistance, faster germination with dodecylamine and slower germination with Ca2+ -dipicolinic acid (CaDPA) than 2xSG plate spores. CSA-13 triggered CaDPA release from spores, an early step in germination, but only well at 70°C and better with spores made on LB than on 2xSG plates. Approximately 90% of spores with elevated levels of SpoVA proteins that form a CaDPA release channel, released CaDPA with CSA-13 at 70°C, and faster with spores made on LB than 2xSG plates. Levels of CSA-13 killing of spores made on LB and 2xSG plates were similar to levels of CaDPA release triggered by this agent. CONCLUSIONS: CSA-13 kills bacterial spores, but only at high concentrations and temperatures, and is preceded by CaDPA release. SIGNIFICANCE AND IMPACT OF THE STUDY: CSA-13 is not a direct sporicide as reported previously, but most likely germinates spores via activation of spores' CaDPA channel, albeit inefficiently, and then killing the germinated spores.


Assuntos
Anti-Infecciosos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Meios de Cultura/química , Meios de Cultura/farmacologia , Esporos Bacterianos/efeitos dos fármacos , Esporos Bacterianos/crescimento & desenvolvimento , Esteroides/farmacologia , Aminas , Ácidos Picolínicos/metabolismo , Esporos Bacterianos/metabolismo
10.
Fitoterapia ; 136: 104171, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31085309

RESUMO

Seven undescribed C21 steroids, namely cynanchin A-G, together with thirteen known analogues, were isolated from the roots of cynanchum otophyllum. Their structures were elucidated by 1D, 2D NMR and MS spectra, as well as chemical methods. Meanwhile, all of isolates were tested for their anti-hepatic fibrosis activity. Among them, compounds 4-6, 10-12 and 14-17 showed moderate or significant inhibitory effects for the proliferation of hepatic stellate cells (HSCs) induced by transforming growth factor-ß1 (TGF-ß1) in vitro.


Assuntos
Cynanchum/química , Células Estreladas do Fígado/efeitos dos fármacos , Raízes de Plantas/química , Esteroides/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Esteroides/isolamento & purificação , Fator de Crescimento Transformador beta1
11.
Mar Drugs ; 17(5)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060323

RESUMO

High intraocular pressure (IOP)-induced retinal ischemia leads to acute glaucoma, which is one of the leading causes of irreversible visual-field loss, characterized by loss of retinal ganglion cells (RGCs) and axonal injury in optic nerves (ONs). Oxidative stress and the inflammatory response play an important role in the ischemic injury of retinal and optic nerves. We focus on 5α-androst-3ß, 5α, 6ß-triol (TRIOL), a synthetic neuroactive derivative of natural marine steroids 24-methylene-cholest-3ß, 5α, 6ß, 19-tetrol and cholestane-3ß, 5α, 6ß-triol, which are two neuroactive polyhydroxysterols isolated from the soft coral Nephthea brassica and the gorgonian Menella kanisa, respectively. We previously demonstrated that TRIOL was a neuroprotective steroid with anti-inflammatory and antioxidative activities. However, the potential role of TRIOL on acute glaucoma and its underlying mechanisms remains unclear. Here, we report TRIOL as a promising neuroprotectant that can protect RGCs and their axons/dendrites from ischemic-reperfusion (I/R) injury in an acute intraocular hypertension (AIH) model. Intravitreal injection of TRIOL significantly alleviated the loss of RGCs and the damage of axons and dendrites in rats and mice with acute glaucoma. As NF-E2-related factor 2 (Nrf2) is one of the most critical regulators in oxidative and inflammatory injury, we further evaluated the effect of TRIOL on Nrf2 knockout mice, and the neuroprotective role of TRIOL on retinal ischemia was not observed in Nrf2 knockout mice, indicating that activation of Nrf2 is responsible for the neuroprotection of TRIOL. Further experiments demonstrated that TRIOL can activate and upregulate Nrf2, along with its downstream hemeoxygenase-1 (HO-1), by negative regulation of Kelch-like ECH (Enoyl-CoA Hydratase) associated Protein-1 (Keap1). In conclusion, our study shed new light on the neuroprotective therapy of retinal ischemia and proposed a promising marine drug candidate, TRIOL, for the therapeutics of acute glaucoma.


Assuntos
Androstanóis/farmacologia , Fator 2 Relacionado a NF-E2/deficiência , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Células Ganglionares da Retina/efeitos dos fármacos , Esteroides/farmacologia , Animais , Técnicas de Cultura de Células , Hipóxia Celular/efeitos dos fármacos , Modelos Animais de Doenças , Glaucoma , Heme Oxigenase-1/metabolismo , Inflamação/tratamento farmacológico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Hipertensão Ocular/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
12.
BMC Infect Dis ; 19(1): 369, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046689

RESUMO

BACKGROUND: Urinary tract infections (UTIs) are one of the most common bacterial infections. High recurrence rates and the increasing antibiotic resistance among uropathogens constitute a large social and economic problem in current public health. We assumed that combination of treatment that includes the administration ceragenins (CSAs), will reinforce the effect of antimicrobial LL-37 peptide continuously produced by urinary tract epithelial cells. Such treatment might be an innovative approach to enhance innate antibacterial activity against multidrug-resistant E. coli. METHODS: Antibacterial activity measured using killing assays. Biofilm formation was assessed using crystal violet staining. Viability of bacteria and bladder epithelial cells subjected to incubation with tested agents was determined using MTT assays. We investigated the effects of chosen molecules, both alone and in combinations against four clinical strains of E. coli, obtained from patients diagnosed with recurrent UTI. RESULTS: We observed that the LL-37 peptide, whose concentration increases at sites of urinary infection, exerts increased bactericidal effect against E. coli when combined with ceragenins CSA-13 and CSA-131. CONCLUSION: We suggest that the employment of combination of natural peptide LL-37 with synthetic analogs might be a potential solution to treat urinary tract infections caused by drug-resistant bacteria.


Assuntos
Antibacterianos/uso terapêutico , Esteroides/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Humanos , Esteroides/farmacologia , Infecções Urinárias/microbiologia
13.
J Anim Sci ; 97(5): 2270-2278, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-30950490

RESUMO

Intramuscular collagen may affect the value of meat by limiting its tenderness and cooking convenience. Production factors such as age of animal at slaughter, the use of steroids and beta-adrenergic agonists as growth promotants, and cattle breed may affect the contribution of collagen to beef quality. Recent research has indicated that concentrations of the mature collagen cross-link pyridinoline (PYR) are positively correlated with Warner-Bratzler shear force (WBSF) and animal age at slaughter, while contribution of the concentration of a second mature collagen cross-link Ehrlich's Chromogen (EC) to beef toughness declines with cattle age. Cattle breed influences total collagen content of muscle due to differing rates of maturation among breeds. Growth promoting technologies do not appear to affect collagen solubility, but do influence PYR and EC densities and concentrations in some beef muscles. Concentrations of PYR and EC do not account for all the variation in collagen heat solubility in beef muscles, nor do advanced glycation end products given the relative immaturity of cattle at slaughter. In light of this, other collagen cross-links such as heat-stable divalent cross-links may warrant reconsideration with regard to their contribution to cooked beef toughness.


Assuntos
Bovinos/fisiologia , Colágeno/química , Carne Vermelha/análise , Agonistas Adrenérgicos beta/farmacologia , Aminoácidos/química , Animais , Bovinos/crescimento & desenvolvimento , Culinária , Esteroides/farmacologia , Paladar
14.
Phytomedicine ; 59: 152789, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31009851

RESUMO

BACKGROUND: Anemarrhena asphodeloides has been widely used in traditional medicine for thousands of years; it has been reported to improve learning and memory, and to reduce inflammation. However, the role of A. asphodeloides in enhancing the immune response has remained unclear. PURPOSE: This study aimed to evaluate the effect of A. asphodeloides extract (AA-Ex) on enhancing the immune response in macrophages and to identify the active compounds causing these effects. STUDY DESIGN/METHODS: To determine the enhancing immune response of AA-Ex and its active compounds, cell proliferation and cell cycle of RAW 264.7 cells were analyzed by MTS assay and flow cytometry. The gene expression of p53, p27, cyclin D2, and cyclin E2 was measured by real-time PCR. To evaluate the anti-inflammatory effects of AA-Ex and its active compounds, the production of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory cytokines was analyzed by Griess reagent, flow cytometry, and real-time PCR. The phosphorylation of p38, c-Jun N-terminal kinase, inhibitory kappa B alpha, and p65 was examined by western blot analysis. RESULTS: AA-Ex increased cell proliferation by extending the cell cycle S-phase; timosaponin B and timosaponin B-II affected cell proliferation and the cell cycle as active compounds of A. asphodeloides. Next, we determined that A. asphodeloides displayed anti-inflammatory effects, including the inhibition of the production of NO, ROS, and pro-inflammatory cytokines through the suppression of mitogen-activated protein kinase and nuclear factor kappa B phosphorylation downstream of the toll-like receptor 4 signaling pathway. Moreover, we identified that timosaponin B and timosaponin B-II were the active compounds for these effects. CONCLUSION: Our results suggest that A. asphodeloides promotes the immune response and has anti-inflammatory effects. Moreover, timosaponin B and B-II played important roles as the active compounds of A. asphodeloides in enhancing the immune and anti-inflammatory responses in this model.


Assuntos
Anemarrhena/química , Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/imunologia , Citocinas/genética , Citocinas/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/imunologia , Plantas Medicinais/química , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Esteroides/farmacologia , Receptor 4 Toll-Like/metabolismo
15.
Chem Biodivers ; 16(6): e1800692, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30957385

RESUMO

Marine natural products display a wide range of biological activities, which play a vital role in the innovation of lead compounds for the drug development. Soft corals have been ranked at the top in regard to the discovery of bioactive metabolites with potential pharmaceutical applications. Many of the isolated cembranoids revealed diverse biological activities, such as anticancer, antidiabetic and anti-osteoporosis. Likewise, sterols from soft corals exhibited interesting biological potential as anti-inflammatory, antituberculosis and anticancer. Consequently, investigating marine soft corals will definitely lead to the discovery of a large number of chemically varied secondary metabolites with countless bioactivities for possible applications in medicine and pharmaceutical industry. This review provides a complete survey of all metabolites isolated from the family Nephtheidae, from 2011 until November 2018, along with their natural sources and biological potential whenever possible.


Assuntos
Antozoários/química , Produtos Biológicos/química , Animais , Antozoários/metabolismo , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia
16.
Eur J Med Chem ; 171: 434-461, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30928713

RESUMO

γ-Aminobutyric acid (GABA) is the major inhibitory transmitter controlling synaptic transmission and neuronal excitability. It is present in a high percentage of neurons in the central nervous system (CNS) and also present in the peripheral nervous system, and acts to maintain a balance between excitation and inhibition. GABA acts via three subclasses of receptors termed GABAA, GABAB, and GABAC. GABAA and GABAC receptors are ligand-gated ion channels, while GABAB receptors are G-protein coupled receptors. Each class of GABA receptor has distinct pharmacology and physiology. GABAA receptors are heteropentameric transmembrane protein complexes made up of α1-6, ß1-3, γ1-3, δ, ε, θ, π subunits, giving rise to numerous allosteric binding sites and have thus attracted much attention targets for the treatment of conditions such as epilepsy, anxiety and sleep disorders. The development of ligands for these binding sites has also led to an improved understanding of the different physiological functions and pathological processes and offers the opportunity for the development of novel therapeutics. This review focuses on the medicinal chemistry aspects including drug design, structure-activity relationships (SAR), and mechanism of actions of GABA modulators, including non-benzodiazepine ligands at the benzodiazepine binding site and modulators acting at sites other than the high-affinity benzodiazepine binding site. Recent advances in this area their future applications and potential therapeutic effects are also highlighted.


Assuntos
Moduladores GABAérgicos/farmacologia , Receptores de GABA/metabolismo , Sítio Alostérico/efeitos dos fármacos , Carbolinas/química , Carbolinas/farmacologia , Etomidato/química , Etomidato/farmacologia , Moduladores GABAérgicos/química , Compostos Heterocíclicos com 2 Anéis/química , Compostos Heterocíclicos com 2 Anéis/farmacologia , Ligantes , Estrutura Molecular , Propofol/química , Propofol/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Esteroides/química , Esteroides/farmacologia
17.
Cell Mol Neurobiol ; 39(4): 471-472, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30941611

RESUMO

Steroids are complex molecules, exerting known and still unknown effects in the nervous system. Throughout this volume, the reader will find a wide spectrum of articles, giving an up-to-date account of the molecular, physiological, pharmacological, and clinical aspects of steroid action on the nervous system.


Assuntos
Sistema Nervoso/efeitos dos fármacos , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo , Esteroides/farmacologia , Animais , Humanos , Camundongos , Neuroproteção/efeitos dos fármacos
18.
Pharm Biol ; 57(1): 176-183, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30860934

RESUMO

CONTEXT: Ophiopogonis Radix, the root of Ophiopogon japonicus (Thunb.) Ker-Gawl (Liliaceae), is a Traditional Chinese Medicine, which has been investigated to possess effective treatment of cardiovascular diseases. OBJECTIVE: This study evaluates the cardioprotective effects of steroidal saponins extract from Ophiopogon japonicus (SOJ) root against doxorubicin-induced chronic heart failure (CHF) through the amelioration of oxidative stress and inflammation. MATERIALS AND METHODS: A Sprague-Dawley rat model of CHF was established by intraperitoneally injected with DOX. All rats were randomly divided into four groups: Control group, CHF group, CHF + SOJ (100 mg/kg) treatment group, SOJ (100 mg/kg) treatment group (n = 8/group). After six weeks administration, biometric and echocardiography were measured. The levels of biochemical parameters were measured using commercial kits. RESULTS: The values of LVESP, +dP/dtmax, -dP/dtmax, EF and FS increased to 116.20 ± 1.68 mmHg, 2978.71 ± 168.26 mmHg/s, 3452.61 ± 286.09 mmHg/s, 68.26 ± 5.28% and 31.97 ± 3.79%, respectively; the values of LVEDP, LVESD and LVEDD decreased to 8.85 ± 0.84 mmHg, 8.39 ± 0.45 mm and 12.36 ± 0.87 mm in CHF + SOJ group. In addition, the levels of IL-6, TNF-α and IL-1ß decreased to 154.41 ± 7.72 pg/mg protein, 110.02 ± 6.96 pg/mg protein and 39.39 ± 5.27 pg/mg protein, respectively; the relative activity of p38 MAPK decreased to 2.60 ± 0.40 in CHF + SOJ group. Furthermore, the activities of SOD, CAT and GSH-Px increased to 268.77 ± 6.20 U/mg protein, 13.68 ± 0.68 U/mg protein and 316.90 ± 8.08 µmol/mg protein, and the content of MDA decreased to 4.03 ± 0.43 nmol/mg protein in CHF + SOJ group. CONCLUSIONS: SOJ exerts the cardioprotective effect against DOX-induced CHF through suppressing inflammatory and oxidative stress. These results provide evidence that SOJ might be an effective treatment for CHF.


Assuntos
Cardiotônicos/farmacologia , Insuficiência Cardíaca/prevenção & controle , Ophiopogon/química , Saponinas/farmacologia , Animais , Cardiotônicos/isolamento & purificação , Doença Crônica , Doxorrubicina/toxicidade , Ecocardiografia , Insuficiência Cardíaca/induzido quimicamente , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Masculino , Medicina Tradicional Chinesa/métodos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Saponinas/isolamento & purificação , Esteroides/isolamento & purificação , Esteroides/farmacologia
19.
Gen Comp Endocrinol ; 277: 56-65, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878349

RESUMO

Unlike its paralog Foxl2, which is well known for its role in ovarian development in vertebrates, the function of Foxl3 is still unclear. Foxl3 is an ancient duplicated copy of Foxl2. It is present as a single copy in ray-finned fish. But, due to repeated losses, it is absent in most tetrapods. Our transcriptomic data, however, show that two Foxl3s (Foxl3a and its paralog Foxl3b) are present in Japanese eel. Foxl3a is predominantly expressed in the pituitary, and Foxl3b is predominantly expressed in the gills. Both Foxl3s show a sex-dimorphic expression, being higher expression in testes than in ovaries. Moreover, Foxl3a and Foxl3b were exclusively expressed during gonadal differentiation in control eels (100% male). Conversely, Foxl3a and Foxl3b significantly decreased after gonadal differentiation in E2-treated eels (100% female). Furthermore, in accordance the difference in adhesive ability between somatic cells and germline cells in testes, Foxl3s showed a high expression in suspension cells (putative germline cells) and low expression in adhesive cells (putative somatic cells). In situ hybridization further showed that Foxl3a and Foxl3b were expressed in the testicular germline cells. In addition, Foxl3s expression was not changed by sex steroids in in vitro testes culture. Taken together, our results suggest that the teleost-specific Foxl3 paralog was repeatedly lost in most fish after the third round of whole genome duplication. The two germline-expressed Foxl3s had higher expression levels in males than in females during gonadal differentiation in Japanese eel. These results demonstrated that Foxl3s might play an important role in germline sexual fate determination from ancient fish to modern fish.


Assuntos
Anguilla/genética , Anguilla/fisiologia , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica no Desenvolvimento , Células Germinativas/metabolismo , Gônadas/fisiologia , Diferenciação Sexual/fisiologia , Sequência de Aminoácidos , Animais , Tamanho Corporal/efeitos dos fármacos , Estradiol/farmacologia , Fatores de Transcrição Forkhead/química , Fatores de Transcrição Forkhead/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Células Germinativas/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Masculino , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Diferenciação Sexual/efeitos dos fármacos , Diferenciação Sexual/genética , Esteroides/farmacologia , Testículo/citologia , Testículo/efeitos dos fármacos , Testículo/metabolismo
20.
Oncol Rep ; 41(5): 2937-2944, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896824

RESUMO

Timosaponin A­III (TAIII) is a saponin isolated from anemarrhena asphodeloides and possesses the inhibitory effect on proliferation of multiple tumor cells. In the present study, the antitumor effect of TAIII and its underlying molecular mechanisms were investigated in vitro in T­cell acute lymphoblastic leukemia (T­ALL) Jurkat cells. The results demonstrated that TAIII inhibits the viability of Jurkat cells in a time­ and dose­dependent manner, and induces apoptosis of Jurkat cells in a dose­dependent manner. Transmission electron microscopy demonstrated the formation of numerous autophagosomes in TAIII­treated Jurkat cells. Furthermore, monodansylcadaverine (MDC)­labeled autophagic vacuoles were observed following TAIII treatment by an inverted fluorescence microscope and MDC accumulation increased notably in TAIII treatment groups in a concentration­dependent manner. B­cell lymphoma­2 (Bcl­2)­associated X (Bax) was upregulated while Bcl­2 was reduced following TAIII treatment, indicating that the pro­apoptotic mechanism of TAIII may be associated with upregulation of Bax. Further investigation revealed that TAIII promotes the expression of autophagy­associated proteins Beclin 1 and LC3­II, and inhibits the phosphoinositide 3­kinase/Akt/mechanistic target of rapamycin kinase pathway. The present study revealed that the antitumor activity of TAIII was primarily achieved by the induction of cell apoptosis and autophagy, indicating a promising potential as a novel effective reagent against T­ALL.


Assuntos
Autofagia/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células Jurkat , Fosfatidilinositol 3-Quinases/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/uso terapêutico , Esteroides/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo
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