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1.
BMJ Paediatr Open ; 8(1)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599800

RESUMO

OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. DESIGN: Phase 3 double-blind randomised placebo-controlled trial. SETTING: Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa. PARTICIPANTS: 1682 children of black African ancestry attending government primary schools and aged 6-11 years at baseline. INTERVENTIONS: Oral vitamin D3 (10 000 IU/week) versus placebo for 3 years. MAIN OUTCOME MEASURES: Height-for-age and body mass index-for-age, measured in all participants; Tanner scores for pubertal development, spirometric lung volumes and body composition, measured in a subset of 450 children who additionally took part in a nested substudy. RESULTS: Mean serum 25-hydroxyvitamin D3 concentration at 3-year follow-up was higher among children randomised to receive vitamin D versus placebo (104.3 vs 64.7 nmol/L, respectively; mean difference (MD) 39.7 nmol/L, 95% CI 37.6 to 41.9 nmol/L). No statistically significant differences in height-for-age z-score (adjusted MD (aMD) -0.08, 95% CI -0.19 to 0.03) or body mass index-for-age z-score (aMD -0.04, 95% CI -0.16 to 0.07) were seen between vitamin D versus placebo groups at follow-up. Among substudy participants, allocation to vitamin D versus placebo did not influence pubertal development scores, % predicted forced expiratory volume in 1 s (FEV1), % predicted forced vital capacity (FVC), % predicted FEV1/FVC, fat mass or fat-free mass. CONCLUSIONS: Weekly oral administration of 10 000 IU vitamin D3 boosted vitamin D status but did not influence growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02880982, South African National Clinical Trials Register DOH-27-0916-5527.


Assuntos
Colestanos , Deficiência de Vitamina D , Criança , Humanos , Composição Corporal , Colecalciferol/uso terapêutico , Colestanos/uso terapêutico , Suplementos Nutricionais , África do Sul/epidemiologia , Espirometria , Vitamina D/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico , Método Duplo-Cego
2.
Phytochemistry ; 219: 113985, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237845

RESUMO

Ornithogalum thyrsoides Jacq belongs to the Asparagaceae family and is cultivated for ornamental purposes. The authors have previously reported several cholestane- and spirostan-type steroidal glycosides from O. thyrsoides. Conventional TLC analysis of the methanolic bulb extract of O. thyrsoides suggested the presence of unprecedented compounds; therefore, a detailed phytochemical investigation of the extract was performed and 35 steroidal glycosides (1-35), including 21 previously undescribed ones (1-21) were collected. The structures of 1-21 were determined mainly by analyses of their 1H and 13C NMR spectra with the aid of two-dimensional NMR spectroscopy. The isolated compounds were classified into three distinct groups: furostan-type (1, 2, 8-12, and 22), spirostan-type (3-7 and 23-26), and cholestane-type (13-21 and 27-35). Although the C/D-ring junction of the steroidal skeleton is typically trans-oriented, except for some cardiotonic and pregnane-type steroidal derivatives, 7 possess a cis C/D-ring junction. This is the first reported instance of such a configuration in spirostan-type steroidal derivatives, marking it as a finding of significant interest. Compounds 1-35 were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells and SBC-3 human small-cell lung cancer cells. Compounds 3-6, 9, 17-21, 23-25, and 30-35 demonstrated cytotoxicity in a dose-dependent manner with IC50 values ranging from 0.000086 to 18 µM and from 0.00014 to 37 µM toward HL-60 and SBC-3 cells, respectively. Compound 19, which is obtained in a good yield and shows relatively potent cytotoxicity among the undescribed compounds, induces apoptosis in HL-60 cells, accompanied by arresting the cell cycle of HL-60 cells at the G2/M phase. In contrast, 19 causes oxidative stress-associated necrosis in SBC-3 cells. The cytotoxic mechanism of 19 is different between HL-60 and SBC-3 cells.


Assuntos
Colestanos , Leucemia , Neoplasias Pulmonares , Ornithogalum , Espirostanos , Humanos , Células HL-60 , Ornithogalum/química , Glicosídeos/química , Colestanos/química , Esteroides/farmacologia , Esteroides/química , Extratos Vegetais/farmacologia
3.
S Afr Fam Pract (2004) ; 65(1): e1-e6, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37916701

RESUMO

Vitamin D is a fat-soluble molecule referring to the different isoforms, ergocalciferol (D2) and cholecalciferol (D3). Its physiological functions include increasing calcium serum concentrations. 25-hydroxyvitamin D3 (25(OH)D) (Calcifediol), a non-active, circulating instant precursor is seen as a pre-hormone. Studies have shown that a deficiency in calcifediol is related to chronic conditions such as cardiovascular, musculoskeletal, immune system, neurological, and anti-neoplastic functions. Vitamin D supplementation has shown its benefit as prophylaxis and treatment during the coronavirus disease 2019 (COVID-19) pandemic and an increase in the prescribing of vitamin D supplementation has been observed. The intention of this review article is to provide guidance on the recommended dosage regimen as a prophylactic measure during COVID-19 and its use as a supplement in general. From this review article, it is clear that vitamin D has an important role to play not only in COVID-19 but also in various other health aspects of the human body.Contribution: This review article highlighted the role of vitamin D in managing vitamin D deficiency and its role as a supplement in the management of respiratory tract infections, especially COVID-19. This overview can assist physicians in optimising healthcare by optimised dosing recommendations and indications.


Assuntos
COVID-19 , Colestanos , Humanos , Calcifediol , Ergocalciferóis/uso terapêutico , Pandemias , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Suplementos Nutricionais , COVID-19/epidemiologia , COVID-19/prevenção & controle
4.
Nutr Bull ; 48(4): 535-545, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37864477

RESUMO

Vitamin D deficiency is widespread in different populations and regions worldwide and has become a global health issue. The vitamin D status of the population in the Yunnan Province of Southwest China has not been evaluated to date. Therefore, in this study, we evaluated the vitamin D status according to the serum concentrations of 25-hydroxyvitamin D (25(OH)D) in individuals of Yunnan Province, a low-latitude, high-altitude and multiracial region in China. The data on 25(OH)D concentrations from October 2012 to December 2017 were retrospectively collected and assessed using the laboratory information system from 52 950 hospital-based participants (age, 1 day-96 years; females, 73.74%). The serum concentration of 25(OH)D was evaluated using a chemiluminescent immunoassay. The analysis was stratified by sex, age, sampling season, testing year, minority, residential district, latitude, altitude and meteorological factors. Vitamin D status was classified as follows: severe deficiency: <10 ng/mL; deficiency: <20 ng/mL; insufficiency: <30 ng/mL; and sufficiency: ≥30 ng/mL. The results showed that vitamin D deficiency is highly prevalent in Yunnan Province in a hospital-based cohort, with a deficiency and severe deficiency rate of 65.1% and a sufficiency rate of 5.30%. Significantly lower vitamin D levels and sufficiency rates were observed in females than in males (20.13 ± 7.22 ng/mL vs. 17.56 ± 6.66 ng/mL and 8.20% vs. 4.20%; p < 0.01, respectively); in spring and winter (16.93 ± 6.24 ng/mL; 2.97% and 16.38 ± 6.43 ng/mL; 3.06%, respectively) than in summer and autumn (20.23 ± 7.14 ng/mL; 8.02% and 19.10 ± 6.97 ng/mL; 6.61% [p < 0.01], respectively); and in older individuals (0-6 years: 28.29 ± 13.13 ng/mL vs. >60 years: 14.88 ± 8.39 ng/mL; p < 0.01). Relatively higher vitamin D levels were observed in individuals of Yi, Zhuang, Hani, Dai, Miao and Lisu minorities and lower levels in individuals of Hui and Zang minorities compared with those of the Han nationality (p < 0.01). The mean sunlight duration, mean air temperature, maximum ultraviolet value and latitude were significantly correlated with vitamin D levels (r = -0.53, 0.60, 0.31, -0.68, respectively; p < 0.05). These results suggest that vitamin D status is influenced by sex, age, minority, latitude and some meteorological factors in areas with high and low altitudes. Hence, new public health policies, such as advice on sunshine exposure, food fortification and nutrition education, as well as the implementation of vitamin D supplementation programmes must be considered to alleviate vitamin D deficiency in Yunnan province, Southwest China.


Assuntos
Colestanos , Deficiência de Vitamina D , Masculino , Feminino , Humanos , Idoso , Estudos Transversais , Estudos Retrospectivos , Altitude , China/epidemiologia , Vitamina D , Calcifediol , Deficiência de Vitamina D/epidemiologia , Vitaminas
5.
Int J Mol Sci ; 24(4)2023 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-36835539

RESUMO

Irisin is a myokine synthesized by skeletal muscle, which performs key actions on whole-body metabolism. Previous studies have hypothesized a relationship between irisin and vitamin D, but the pathway has not been thoroughly investigated. The purpose of the study was to evaluate whether vitamin D supplementation affected irisin serum levels in a cohort of 19 postmenopausal women with primary hyperparathyroidism (PHPT) treated with cholecalciferol for six months. In parallel, to understand the possible link between vitamin D and irisin, we analyzed the expression of the irisin precursor, Fndc5, in the C2C12 myoblast cell line treated with a biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Our results demonstrate that vitamin D supplementation resulted in a significant increase in irisin serum levels (p = 0.031) in PHPT patients. In vitro, we show that vitamin D treatment on myoblasts enhanced Fndc5 mRNA after 48 h (p = 0.013), while it increased mRNAs of sirtuin 1 (Sirt1) (p = 0.041) and peroxisome proliferator-activated receptor γ coactivator 1α (Pgc1α) (p = 0.017) over a shorter time course. Overall, our data suggest that vitamin-D-induced modulation of Fndc5/irisin occurs through up-regulation of Sirt1, which together with Pgc1α, is an important regulator of numerous metabolic processes in skeletal muscle.


Assuntos
Colestanos , Fibronectinas , Humanos , Feminino , Fibronectinas/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/metabolismo , Músculo Esquelético/metabolismo , Fatores de Transcrição/metabolismo , Vitaminas/metabolismo , Vitamina D/metabolismo
6.
Sci Rep ; 12(1): 16807, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207476

RESUMO

Evidence for an association between the amount of particulate matter (PM) in the atmosphere and vitamin D status of pregnant women is limited. We aimed to examine the independent association between PM and maternal levels of serum 25-hydroxyvitamin D (25OHD) during the second trimester and to explore possible modifications to the association by meteorological factors. 27,768 pregnant women presenting for prenatal examination who were tested for serum 25OHD concentration during the second trimester between January 1, 2016, and December 31, 2020, were included in this retrospective analysis. Exposure to PM was evaluated based on daily average PM with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) and PM with an aerodynamic diameter of ≤ 10 µm (PM10). Corresponding meteorological data for daily average atmospheric temperature, atmospheric pressure, relative humidity, sunshine duration, and wind speed were collected. The maximum cumulative effects of PM2.5 occurred at lag 45 days, and the maximum cumulative effects of PM10 occurred at lag 60 days. In crude models, 45-day moving daily average PM2.5 concentrations were negatively associated with 25OHD levels (ß, - 0.20; 95% CI - 0.21 to - 0.19), as were 60-day moving daily average PM10 concentrations (ß, - 0.14; 95% CI - 0.15 to - 0.14). After adjusting for temporal and meteorological factors, the effect values were drastically reduced (adjusted ß of PM2.5, - 0.032; 95% CI - 0.046 to - 0.018; adjusted ß of PM10, - 0.039; 95% CI - 0.049 to - 0.028). Our study showed there was a small, independent, negative association between PM in the atmosphere and maternal serum 25OHD levels during the second trimester of pregnancy after adjusting for temporal and/or meteorological factors, which indicates that PM may have a limited influence on maternal serum 25OHD levels. Besides taking vitamin D supplements, pregnant women should keep participating in outdoor activities while taking PM protection measures to improve their vitamin D levels when PM levels are high in winter and spring.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Colestanos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Feminino , Humanos , Conceitos Meteorológicos , Material Particulado/análise , Gravidez , Estudos Retrospectivos , Estações do Ano , Vitamina D/análise , Vitaminas/análise
7.
Fitoterapia ; 158: 105174, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35296434

RESUMO

Five new cholestane glycosides, named parisfargosides A-E (1-5), were isolated from the rhizomes of Paris fargesii. Their structures were elucidated on the basis of UV, HR-ESI-MS, 1D and 2D NMR data as well as chemical methods. The structures of all compounds contained α, ß-unsaturated ketone unit. Compounds 3-5 possessed a 16,23-cyclocholest skeleton with 6/6/6/5/5 condensed ring, and the absolute configurations of C-16 and C-23 were confirmed according to ROESY spectra with pyridine­d5 and DMSO­d6 as solvents. In addition, the platelet aggregation activity and cytotoxic activity against five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480) of compounds 1-5 were evaluated.


Assuntos
Colestanos , Liliaceae , Colestanos/farmacologia , Glicosídeos/química , Humanos , Estrutura Molecular , Rizoma/química
8.
J Asian Nat Prod Res ; 24(7): 663-672, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34292111

RESUMO

Ornithogalum caudatum Ait (OCA) is a natural product used in Chinese traditional medicine. The cholestane saponin OSW-1 is isolated from plant OCA and has recently been shown to have potent cytotoxic effects against different types of cancers. The therapeutic efficacy of OSW-1 on prostate cancer and its underlying mechanism are yet to be established. OSW-1 inhibited the growth of prostate cancer cells by interrupting the interaction between mTOR and Rictor/mTORC2. This mechanism showed a better therapeutic outcome than that of the conventional inhibition of mTOR and provided a basis for as sisting modern prostate cancer treatment strategies.


Assuntos
Colestanos , Ornithogalum , Neoplasias da Próstata , Saponinas , Colestenonas , Humanos , Masculino , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Estrutura Molecular , Ornithogalum/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Saponinas/farmacologia , Serina-Treonina Quinases TOR/metabolismo
9.
Am J Physiol Cell Physiol ; 321(3): C569-C584, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34288720

RESUMO

Rheumatoid arthritis (RA) is a debilitating autoimmune disease of unknown cause, characterized by infiltration and accumulation of activated immune cells in the synovial joints where cartilage and bone destructions occur. Myeloid-derived suppressor cells (MDSCs) are of myeloid origin and are able to suppress T cell responses. Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) was shown to be involved in the regulation of MDSC differentiation. The purpose of the present study was to investigate the effect of inhibition of SHIP1 on the expansion of MDSCs in RA using a collagen-induced inflammatory arthritis (CIA) mouse model. In DBA/1 mice, treatment with a small molecule-specific SHIP1 inhibitor 3α-aminocholestane (3AC) induced a marked expansion of MDSCs in vivo. Both pretreatment with 3AC of DBA/1 mice prior to CIA induction and intervention with 3AC during CIA progression significantly reduced disease incidence and severity. Adoptive transfer of MDSCs isolated from 3AC-treated mice, but not naïve MDSCs from normal mice, into CIA mice significantly reduced disease incidence and severity, indicating that the 3AC-induced MDSCs were the cellular mediators of the observed amelioration of the disease. In conclusion, inhibition of SHIP1 expands MDSCs in vivo and attenuates development of CIA in mice. Small molecule-specific inhibition of SHIP1 may therefore offer therapeutic benefit to patients with RA and other autoimmune diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Colestanos/farmacologia , Células Supressoras Mieloides/imunologia , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Animais , Artrite Experimental/genética , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Comunicação Celular , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Expressão Gênica , Humanos , Cápsula Articular/efeitos dos fármacos , Cápsula Articular/imunologia , Cápsula Articular/patologia , Camundongos , Camundongos Endogâmicos DBA , Camundongos Knockout , Células Supressoras Mieloides/citologia , Células Supressoras Mieloides/transplante , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/antagonistas & inibidores , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/imunologia , Índice de Gravidade de Doença , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/patologia
10.
Sci Rep ; 10(1): 20590, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239727

RESUMO

Vitamin D plays a critical role in calcium homeostasis and in the maintenance and development of skeletal health. Vitamin D status has increasingly been linked to non-skeletal health outcomes such as all-cause mortality, infectious diseases and reproductive outcomes in both humans and veterinary species. We have previously demonstrated a relationship between vitamin D status, assessed by the measurement of serum concentrations of the major vitamin D metabolite 25 hydroxyvitamin D (25(OH)D), and a wide range of non-skeletal health outcomes in companion and wild animals. The aims of this study were to define the host and environmental factors associated with vitamin D status in a cohort of 527 calves from Western Kenya which were part of the Infectious Disease of East African Livestock (IDEAL) cohort. A secondary aim was to explore the relationship between serum 25(OH)D concentrations measured in 7-day old calves and subsequent health outcomes over the following 12 months. A genome wide association study demonstrated that both dietary and endogenously produced vitamin D metabolites were under polygenic control in African calves. In addition, we found that neonatal vitamin D status was not predictive of the subsequent development of an infectious disease event or mortality over the 12 month follow up period.


Assuntos
Bovinos/metabolismo , Vitamina D/análogos & derivados , Vitamina D/análise , Animais , Animais Recém-Nascidos/sangue , Animais Recém-Nascidos/metabolismo , Animais Lactentes/sangue , Animais Lactentes/metabolismo , Calcifediol , Bovinos/sangue , Colestanos , Estudos de Coortes , Dieta , Suplementos Nutricionais , Feminino , Estudo de Associação Genômica Ampla , Quênia , Masculino , Vitamina D/sangue , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/veterinária , Vitaminas
11.
J Nat Prod ; 83(4): 1043-1050, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32227943

RESUMO

An extract of Galtonia regalis from the Natural Products Discovery Institute showed moderate antiplasmodial activity, with an IC50 value less than 1.25 µg/mL. The two known cholestane glycosides 1 and 2 and the five new cholestane glycosides galtonosides A-E (3-7) were isolated after bioassay-directed fractionation. The structures of the new compounds were determined by interpretation of their NMR and mass spectra. Among these compounds, galtonoside B (4) displayed the most potent antiplasmodial activity, with an IC50 value of 0.214 µM against the drug-resistant Dd2 strain of Plasmodium falciparum.


Assuntos
Antimaláricos/química , Colestanos/farmacologia , Glicosídeos/farmacologia , Asparagales/química , Colestanos/química , Colestanos/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plasmodium falciparum/química
12.
Cell Rep ; 28(11): 2905-2922.e5, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509751

RESUMO

The importance of hypothalamic leptin and insulin resistance in the development and maintenance of obesity remains unclear. The tyrosine phosphatases protein tyrosine phosphatase 1B (PTP1B) and T cell protein tyrosine phosphatase (TCPTP) attenuate leptin and insulin signaling and are elevated in the hypothalami of obese mice. We report that elevated PTP1B and TCPTP antagonize hypothalamic leptin and insulin signaling and contribute to the maintenance of obesity. Deletion of PTP1B and TCPTP in the hypothalami of obese mice enhances CNS leptin and insulin sensitivity, represses feeding, and increases browning, to decrease adiposity and improve glucose metabolism. The daily intranasal administration of a PTP1B inhibitor, plus the glucocorticoid antagonist RU486 that decreases TCPTP expression, represses feeding, increases browning, promotes weight loss, and improves glucose metabolism in obese mice. Our findings causally link heightened hypothalamic PTP1B and TCPTP with leptin and insulin resistance and the maintenance of obesity and define a viable pharmacological approach by which to promote weight loss in obesity.


Assuntos
Hipotálamo/metabolismo , Resistência à Insulina/genética , Leptina/metabolismo , Obesidade/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 2/metabolismo , Redução de Peso/genética , Tecido Adiposo Branco/metabolismo , Administração Intranasal , Animais , Barreira Hematoencefálica/metabolismo , Colestanos/administração & dosagem , Dieta Hiperlipídica , Comportamento Alimentar/efeitos dos fármacos , Gliose/genética , Gliose/metabolismo , Glucocorticoides/farmacologia , Hipotálamo/efeitos dos fármacos , Leptina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mifepristona/administração & dosagem , Obesidade/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Espermina/administração & dosagem , Espermina/análogos & derivados
13.
Nat Commun ; 10(1): 225, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30644384

RESUMO

Transient oligomeric species formed during the aggregation process of the 42-residue form of the amyloid-ß peptide (Aß42) are key pathogenic agents in Alzheimer's disease (AD). To investigate the relationship between Aß42 aggregation and its cytotoxicity and the influence of a potential drug on both phenomena, we have studied the effects of trodusquemine. This aminosterol enhances the rate of aggregation by promoting monomer-dependent secondary nucleation, but significantly reduces the toxicity of the resulting oligomers to neuroblastoma cells by inhibiting their binding to the cellular membranes. When administered to a C. elegans model of AD, we again observe an increase in aggregate formation alongside the suppression of Aß42-induced toxicity. In addition to oligomer displacement, the reduced toxicity could also point towards an increased rate of conversion of oligomers to less toxic fibrils. The ability of a small molecule to reduce the toxicity of oligomeric species represents a potential therapeutic strategy against AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Colestanos/uso terapêutico , Fragmentos de Peptídeos/metabolismo , Espermina/análogos & derivados , Peptídeos beta-Amiloides/efeitos dos fármacos , Animais , Caenorhabditis elegans , Linhagem Celular Tumoral , Colestanos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Fragmentos de Peptídeos/efeitos dos fármacos , Espermina/farmacologia , Espermina/uso terapêutico
14.
J Nat Med ; 73(1): 131-145, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30327993

RESUMO

A search for cytotoxic cholestane glycosides from Ornithogalum saundersiae bulbs resulted in the isolation of three new OSW-1 analogues (1-3), a new cholestane bisdesmoside (4), a 5ß-cholestane diglycoside (5), and four new 24(23 → 22)-abeo-cholestane glycosides (6-9), together with 11 known cholestane glycosides (10-20), including OSW-1 (11). The structures of 1-9 were determined based on conventional spectroscopic analysis and chemical evidence. As expected, based on previous data, 1-3 exhibited potent cytotoxic activity against HL-60 human promyelocytic leukemia cells and A549 human lung adenocarcinoma cells. Furthermore, the ability of OSW-1 to induce apoptosis in HL-60 cells was examined. Aggregation of nuclear chromatin, accumulation of the sub-G1 cells, DNA fragmentation, and caspase-3 activation were assessed in HL-60 cells treated with OSW-1, providing evidence for OSW-1-induced apoptosis in HL-60 cells. No mitochondrial membrane potential or release of cytochrome c into the cytoplasm were observed in the OSW-1-treated apoptotic HL-60 cells, indicating that a mitochondria-independent signaling pathway is involved in apoptotic cell death.


Assuntos
Colestanos/química , Colestenonas/metabolismo , Glicosídeos/química , Células HL-60/metabolismo , Mitocôndrias/metabolismo , Ornithogalum/química , Saponinas/metabolismo , Apoptose , Humanos , Transdução de Sinais
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 210: 372-380, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30502725

RESUMO

Ganoderic Acids (GAs) are the major medicinal compounds in Ganoderma lucidum used as traditional Chinese medicine since ancient times. Ganoderic acid A (GAA) is the first discovered ganoderic acids reported in the literature, which is also one of most abundant triterpenoids of Ganoderma lucidum. Especially, GAA has been extensively investigated in recent decades for its positive medicinal activities. However, the vibrational properties of GAs have rarely been studied or reported. In this work, we focused on the typical GAA and studied the infrared (IR) and Raman spectra based on both experiments and DFT calculations. As such, we could not only achieve the assignments of the vibrational modes, but also from the IR and Raman spectra, we found that the spectral region from 1500 cm-1 to 1800 cm-1 is particularly useful for distinguishing different types of GAs. In addition, its dehydrogenated derivative ganoderenic acid A (GOA) was also studied, which could be identified due to its spectral feature of strong IR and Raman bands around 1620 cm-1. This work therefore may facilitate the application of IR and Raman spectroscopies in the inspection and quality control of Ganoderma lucidum.


Assuntos
Ácidos Heptanoicos/química , Lanosterol/análogos & derivados , Espectrofotometria Infravermelho/métodos , Análise Espectral Raman/métodos , Colestanos/química , Teoria da Densidade Funcional , Lanosterol/química , Estrutura Molecular , Reishi/química , Espectroscopia de Infravermelho com Transformada de Fourier , Vibração
16.
Fitoterapia ; 130: 241-246, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30196076

RESUMO

Three new cholestane-type sterols bearing an unusual ∆22-24-oxo side chain, namely, dictyoptesterols A-C (1-3), were isolated from the brown alga Dictyopteris undulata Holmes, together with five known strutural analogues (4-8). Their structures were elucidated on the basis of by extensive spectroscopic analysis. The absolute configurations of the steroidal nuclei of the new compounds were proposed by a comparison of NMR data with those of related known compounds as well as biogenetic considerations. All of the isolates were evaluated in vitro for their potential to inhibit protein tyrosine phosphatase-1B (PTP1B) activity. The results showed that compounds 1-5 exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 3.03 ±â€¯0.76 to 15.01 ±â€¯2.88 µM. In particular, compounds 3 and 4 showed promising inhibitory effects towards PTP1B with IC50 values of 3.03 ±â€¯0.76 and 3.72 ±â€¯0.40 µM, respectively, when compared to the positive control oleanolic acid (IC50, 2.83 ±â€¯0.39 µM). The chemotaxonomic significance of these isolated ∆22-24-oxo cholestanes has also been discussed.


Assuntos
Colestanos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Phaeophyceae/química , Fitosteróis/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , China , Colestanos/farmacologia , Inibidores Enzimáticos/farmacologia , Estrutura Molecular , Fitosteróis/farmacologia
17.
Phytochemistry ; 136: 125-132, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28139298

RESUMO

Phytochemical investigation of the tubers of Ophiopogon japonicus led to the isolation of five previously undescribed steroidal saponins, ophiojaponins A-E, together with twelve known ones. The structures of these isolated compounds were elucidated by detailed spectroscopic analyses and chemical methods. Ophiojaponins A-C are rare naturally occurring C29 steroidal glycosides possessing a homo-cholestane skeleton with an aromatized ring E. Ruscogenin 1-O-α-L-rhamnopyranosyl-(1 â†’ 2)-4-O-sulfo-ß-D-fucopyranosido-3-O-ß-D-glucopyranoside was isolated as single component and its full spectroscopic data was reported for the first time. The isolated steroidal saponins were evaluated for their cytotoxicities against two human tumor cell lines MG-63 and SNU387. Among them, five known spirostane-type glycosides showed cytotoxic activity against both MG-63 and SNU387 cell lines with IC50 values ranging from 0.76 to 27.0 µM.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Colestanos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Ophiopogon/química , Tubérculos/química , Saponinas/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Colestanos/química , Colestanos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Estrutura Molecular , Saponinas/química , Saponinas/farmacologia , Estereoisomerismo
18.
J Steroid Biochem Mol Biol ; 169: 210-218, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27343991

RESUMO

Accumulating evidence indicates that cholesterol oxygenation products, also known as oxysterols (OS), are involved in breast cancer (BC) promotion. The impact of Tam, as well as aromatase inhibitors (AI), an alternative BC endocrine therapy (ET), on OS metabolism in patients is currently unknown. We conducted a prospective clinical study in BC patients receiving Tam (n=15) or AI (n=14) in adjuvant or in metastatic settings. The primary end point was the feasibility of detecting and quantifying 11 different OS in the circulation of patients before and after 28days of treatment with Tam or AI. Key secondary end points were the measurements of variations in the concentrations of OS according to differences between patients and treatments. OS profiling in the serum of patients was determined by gas chromatography coupled to mass spectrometry. OS profiling was conducted in all patients both at baseline and during treatment regimens. An important inter-individual variability was observed for each OS. Interestingly 5,6ß-epoxycholesterol relative concentrations significantly increased in the entire population (p=0.0109), while no increase in Cholestane-triol (CT) levels was measured. Interestingly, we found that, in contrast to AI, Tam therapy significantly decreased blood levels of 24-hydroxycholesterol (24-HC), 7α-HC and 25-HC (a tumor promoter) (p=0.0007, p=0.0231 and p=0.0231, respectively), whereas 4ß-HC levels increased (p=0.0010). Interestingly, levels of 27-HC (a tumor promoter) significantly increased in response to AI (p=0.0342), but not Tam treatment. According to these results, specific OS are promising candidate markers of Tam and AI efficacy. Thus, further clinical investigations are needed to confirm the use of oxysterols as biomarkers of both prognosis and/or the efficacy of ET.


Assuntos
Neoplasias da Mama/sangue , Oxisteróis/metabolismo , Adulto , Idoso , Androstadienos/uso terapêutico , Aromatase/metabolismo , Inibidores da Aromatase/uso terapêutico , Biomarcadores/sangue , Índice de Massa Corporal , Neoplasias da Mama/metabolismo , Colestanos/sangue , Colesterol/análogos & derivados , Colesterol/metabolismo , Estudos de Viabilidade , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Hormônios/química , Humanos , Letrozol , Pessoa de Meia-Idade , Metástase Neoplásica , Nitrilas/uso terapêutico , Estresse Oxidativo , Oxisteróis/sangue , Projetos Piloto , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Transdução de Sinais , Tamoxifeno/uso terapêutico , Triazóis/uso terapêutico
20.
Steroids ; 89: 1-10, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25042471

RESUMO

Six new spirostane glycosides (1-6), named polygodosides A-F, one new furostanol glycoside, polygodoside G (7), one new cholestane glycoside, polygodoside H (8), and one new steroidal sapogenin, polygodosin A (9), together with thirteen known compounds (10-22) were isolated from a 90% MeOH extract of the fibrous roots of Polygonatum odoratum (Mill.) Druce. The structures of new compounds were elucidated by extensive 1D and 2D NMR spectroscopic analyses and mass spectrometry. The effects on TF procoagulant activity in THP-1 cells were tested for most of the compounds.


Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Colestanos/química , Glicosídeos/química , Sapogeninas/química , Esteróis/química , Tromboplastina/metabolismo , Transtornos da Coagulação Sanguínea/metabolismo , Colestanos/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Glicosídeos/isolamento & purificação , Humanos , Estrutura Molecular , Raízes de Plantas/química , Polygonatum/química , Sapogeninas/isolamento & purificação , Esteroides/química , Esteroides/isolamento & purificação , Esteróis/isolamento & purificação , Tromboplastina/antagonistas & inibidores , Tromboplastina/química
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