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2.
Sci Rep ; 14(1): 4756, 2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413628

RESUMO

This study assesses the prevalence of Vitamin D deficiency and its potential association with cardiometabolic risk factors among South African adults residing in the Eastern Cape province. In this cross-sectional study, 1244 healthcare workers (HCWs) completed a self-administered questionnaire and venous blood samples were drawn at two academic hospitals in the Eastern Cape. History of hypertension and diabetes mellitus were self-reported. Participants were categorised as obese if their body mass index (BMI) ≥ 30 kg/m2. Participants were classified as having metabolic syndrome if they had hypertension, diabetes mellitus and obesity. Vitamin D [25(OH)D] deficiency was defined as venous blood concentrations < 50 nmol/L. Associations between vitamin D deficiency and participants' characteristics were assessed using multivariate logistic regression model analysis. The prevalence of vitamin D deficiency was 28.5% (n = 355), of whom 292 were female. Among the participants who were deficient in vitamin D, the prevalence of obesity, diabetes mellitus, hypertension, chronic kidney disease, and metabolic syndrome was 64.9% (n = 230), 9% (n = 32), 16.6% (n = 59), 2.3% (n = 8) and 18% (n = 64), respectively. In the adjusted multivariate logistic regression model, black Africans (AOR = 2.87; 95% CI 1.52-5.43) and individuals ≥ 42 years (AOR = 1.37; 95% CI 1.07-1.77) were more likely to exhibit vitamin D deficiency. However, there was no significant association by age, sex, and cardiometabolic markers. More than one in four healthcare workers was deficient in vitamin D among the study sample, especially the black Africans and older individuals. Further studies are needed at the population level to elucidate on the vitamin D status in the region.


Assuntos
Colestanos , Diabetes Mellitus , Hipertensão , Síndrome Metabólica , Deficiência de Vitamina D , Adulto , Humanos , Feminino , Masculino , Estudos Transversais , África do Sul/epidemiologia , Fatores de Risco , Fatores de Risco Cardiometabólico , Prevalência , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Vitamina D , Obesidade/complicações , Vitaminas , Hipertensão/epidemiologia , Hipertensão/complicações
3.
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
4.
Cells ; 13(2)2024 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-38247843

RESUMO

Equine metabolic syndrome (EMS) is a significant global health concern in veterinary medicine. There is increasing interest in utilizing molecular agents to modulate hepatocyte function for potential clinical applications. Recent studies have shown promising results in inhibiting protein tyrosine phosphatase (PTP1B) to maintain cell function in various models. In this study, we investigated the effects of the inhibitor Trodusquemine (MSI-1436) on equine hepatic progenitor cells (HPCs) under lipotoxic conditions. We examined proliferative activity, glucose uptake, and mitochondrial morphogenesis. Our study found that MSI-1436 promotes HPC entry into the cell cycle and protects them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the cells' morphological architecture. Furthermore, our findings suggest that MSI-1436 enhances 2-NBDG uptake by increasing the expression of SIRT1, which is associated with liver insulin sensitivity. It also promotes mitochondrial dynamics by modulating mitochondria quantity and morphotype as well as increasing the expression of PINK1, MFN1, and MFN2. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in treating EMS and insulin dysregulation.


Assuntos
Colestanos , Resistência à Insulina , Síndrome Metabólica , Dinâmica Mitocondrial , Espermina , Animais , Glucose , Cavalos , Insulina/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Palmitatos , Espermina/análogos & derivados , Resistência à Insulina/fisiologia
5.
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
6.
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
7.
Molecules ; 28(16)2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37630192

RESUMO

The present study describes the synthesis, characterization, and in vitro molecular interactions of a steroid 3ß,6ß-diacetoxy-5α-cholestan-5-ol. Through conventional and solid-state methods, a cholestane derivative was successfully synthesized, and a variety of analytical techniques were employed to confirm its identity, including high-resolution mass spectrometry (HRMS), Fourier transforms infrared (FT-IR), nuclear magnetic resonance (NMR), elemental analysis, and X-ray single-crystal diffraction. Optimizing the geometry of the steroid was undertaken using density functional theory (DFT), and the results showed great concordance with the data from the experiments. Fluorescence spectral methods and ultraviolet-vis absorption titration were employed to study the in vitro molecular interaction of the steroid regarding human serum albumin (HSA). The Stern-Volmer, modified Stern-Volmer, and thermodynamic parameters' findings showed that steroids had a significant binding affinity to HSA and were further investigated by molecular docking studies to understand the participation of active amino acids in forming non-bonding interactions with steroids. Fluorescence studies have shown that compound 3 interacts with human serum albumin (HSA) through a static quenching mechanism. The binding affinity of compound 3 for HSA was found to be 3.18 × 104 mol-1, and the Gibbs free energy change (ΔG) for the binding reaction was -9.86 kcal mol-1 at 298 K. This indicates that the binding of compound 3 to HSA is thermodynamically favorable. The thermodynamic parameters as well as the binding score obtained from molecular docking at various Sudlow's sites was -8.2, -8.5, and -8.6 kcal/mol for Sites I, II, and III, respectively, supporting the system's spontaneity. Aside from its structural properties, the steroid demonstrated noteworthy antioxidant activity, as evidenced by its IC50 value of 58.5 µM, which is comparable to that of ascorbic acid. The findings presented here contribute to a better understanding of the pharmacodynamics of steroids.


Assuntos
Antioxidantes , Colestanos , Humanos , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Ácido Ascórbico
8.
Int J Mol Sci ; 24(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37047445

RESUMO

Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Our study aimed to explore differences in bone alterations between T2DM women and controls and to assess clinical predictors of bone impairment in T2DM. For this observational case control study, we recruited 126 T2DM female patients and 117 non-diabetic, age- and BMI-comparable women, who underwent clinical examination, routine biochemistry and dual-energy X-ray absorptiometry (DXA) scans for bone mineral density (BMD) and trabecular bone score (TBS) assessment-derived indexes. These were correlated to metabolic parameters, such as glycemic control and lipid profile, by bivariate analyses, and significant variables were entered in multivariate adjusted models to detect independent determinants of altered bone status in diabetes. The T2DM patients were less represented in the normal bone category compared with controls (5% vs. 12%; p = 0.04); T2DM was associated with low TBS (OR: 2.47, C.I. 95%: 1.19-5.16, p = 0.016) in a regression model adjusted for age, menopausal status and BMI. In women with T2DM, TBS directly correlated with plasma high-density lipoprotein cholesterol (HDL-c) (p = 0.029) and vitamin D (p = 0.017) levels. An inverse association was observed with menopausal status (p < 0.001), metabolic syndrome (p = 0.014), BMI (p = 0.005), and waist circumference (p < 0.001). In the multivariate regression analysis, lower HDL-c represented the main predictor of altered bone quality in T2DM, regardless of age, menopausal status, BMI, waist circumference, statin treatment, physical activity, and vitamin D (p = 0.029; R2 = 0.47), which likely underlies common pathways between metabolic disease and bone health in diabetes.


Assuntos
Colestanos , Diabetes Mellitus Tipo 2 , Humanos , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos de Casos e Controles , HDL-Colesterol , Densidade Óssea , Osso Esponjoso , Vitamina D/uso terapêutico , Vértebras Lombares
9.
Sci Rep ; 13(1): 4353, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36928441

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has been linked with a number of extra hepatic diseases and could be a potential risk factor of decreasing bone mineral density. To determine whether Upper Egyptian patients with NAFLD are at risk of developing osteoporosis. Cross sectional study was done on a total 100 individuals; 50 patients diagnosed with NAFLD (based on ultrasound imaging) crossed-matched with 50 individuals without NAFLD based on age, sex and body mass index. Bone mineral density, serum calcium and phosphorus levels, serum parathyroid hormone, serum vitamin D and fasting insulin level were assessed. Osteoporosis was prevalent in NAFLD patients versus to controls (19/50 vs. 0/50; P < 0.001). There was significant decrease in bone mineral density in NAFLD patients than controls (- 2.29 ± 0.4 vs. - 1.53 ± 0.1; P < 0.001). There was a statistical significance decrease in serum vitamin D and calcium levels in NAFLD patients than controls. Furthermore, vitamin D levels in the NAFLD group was a predictor for osteoporosis (OR 0.614; 95% CI 0.348-0.825). Patients with NAFLD tend to have a significant decrease in bone density, vitamin D, and serum calcium levels than controls.


Assuntos
Colestanos , Hepatopatia Gordurosa não Alcoólica , Osteoporose , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Densidade Óssea , Cálcio , Estudos Transversais , Egito/epidemiologia , Osteoporose/etiologia , Osteoporose/complicações , Vitamina D , Vitaminas
10.
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
11.
Molecules ; 28(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36677740

RESUMO

During the last decade, the evidence for the biological relevance of i-motif DNA (i-DNA) has been accumulated. However, relatively few molecules were reported to interact with i-DNA, and a controversy concerning their binding mode, affinity, and selectivity persists in the literature. In this context, the cholestane derivative IMC-48 has been reported to modulate bcl-2 gene expression by stabilizing an i-motif structure in its promoter. In the present contribution, we report on a novel, more straightforward, synthesis of IMC-48 requiring fewer steps compared to the previous approach. Furthermore, the interaction of IMC-48 with four different i-motif DNA sequences was thoroughly investigated by bio-layer interferometry (BLI) and circular dichroism (CD) spectroscopy. Surprisingly, our results show that IMC-48 is a very weak ligand of i-DNA as no quantifiable interaction or significant stabilization of i-motif structures could be observed, stimulating a quest for an alternative mechanism of its biological activity.


Assuntos
Colestanos , DNA , Sequência de Bases , DNA/genética , DNA/química , Piperidinas/química , Colestanos/química , Dicroísmo Circular , Ligantes
12.
Molecules ; 27(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36500556

RESUMO

Herein, we describe the synthesis and characterization of fused pyrroles in cholestane and norcholestane side chains derived from kryptogenin and diosgenin, respectively. Both conventional and microwave heating techniques were used to synthesize the steroidal pyrroles from primary amines, with the microwave method producing the highest yields. In particular, the norcholestane pyrroles were tested as acaricides against the two-spotted spider mite (Tetranychus urticae Koch) under laboratory conditions and as plant growth promoters on habanero pepper (Capsicum chinense Jacq) under greenhouse conditions.


Assuntos
Acaricidas , Capsicum , Colestanos , Tetranychidae , Animais , Acaricidas/farmacologia , Pirróis/farmacologia , Capsicum/química
13.
FASEB J ; 36(12): e22655, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36421008

RESUMO

Trodusquemine is an aminosterol with a variety of biological and pharmacological functions, such as acting as an antimicrobial, stimulating body weight loss and interfering with the toxicity of proteins involved in the development of Alzheimer's and Parkinson's diseases. The mechanisms of interaction of aminosterols with cells are, however, still largely uncharacterized. Here, by using fluorescently labeled trodusquemine (TRO-A594 and TRO-ATTO565), we show that trodusquemine binds initially to the plasma membrane of living cells, that the binding affinity is dependent on cholesterol, and that trodusquemine is then internalized and mainly targeted to lysosomes after internalization. We also found that TRO-A594 is able to strongly and selectively bind to myelinated fibers in fixed mouse brain slices, and that it is a marker compatible with tissue clearing and light-sheet fluorescence microscopy or expansion microscopy. In conclusion, this work contributes to further characterize the biology of aminosterols and provides a new tool for nerve labeling suitable for the most advanced microscopy techniques.


Assuntos
Colestanos , Animais , Camundongos , Colestanos/farmacologia , Espermina/farmacologia , Microscopia de Fluorescência/métodos , Colesterol
14.
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
16.
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
17.
Int J Mol Sci ; 23(3)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35162998

RESUMO

This review comprehensively describes the recent advances in the synthesis and pharmacological evaluation of steroid polyamines squalamine, trodusquemine, ceragenins, claramine, and their diverse analogs and derivatives, with a special focus on their complete synthesis from cholic acids, as well as an antibacterial and antiviral, neuroprotective, antiangiogenic, antitumor, antiobesity and weight-loss activity, antiatherogenic, regenerative, and anxiolytic properties. Trodusquemine is the most-studied small-molecule allosteric PTP1B inhibitor. The discovery of squalamine as the first representative of a previously unknown class of natural antibiotics of animal origin stimulated extensive research of terpenoids (especially triterpenoids) comprising polyamine fragments. During the last decade, this new class of biologically active semisynthetic natural product derivatives demonstrated the possibility to form supramolecular networks, which opens up many possibilities for the use of such structures for drug delivery systems in serum or other body fluids.


Assuntos
Organismos Aquáticos/química , Esteroides/química , Esteroides/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Colestanos/química , Colestanóis/química , Humanos , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Espermina/análogos & derivados , Espermina/química , Esteroides/síntese química , Triterpenos/síntese química
18.
Nat Prod Rep ; 39(4): 742-753, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-34698757

RESUMO

Covering: 1993 to 2021 (mainly 2017-2021)Alzheimer's and Parkinson's diseases are neurodegenerative conditions affecting over 50 million people worldwide. Since these disorders are still largely intractable pharmacologically, discovering effective treatments is of great urgency and importance. These conditions are characteristically associated with the aberrant deposition of proteinaceous aggregates in the brain, and with the formation of metastable intermediates known as protein misfolded oligomers that play a central role in their aetiology. In this Highlight article, we review the evidence at the physicochemical, cellular, animal model and clinical levels on how the natural products squalamine and trodusquemine offer promising opportunities for chronic treatments for these progressive conditions by preventing both the formation of neurotoxic oligomers and their interaction with cell membranes.


Assuntos
Doença de Alzheimer , Produtos Biológicos , Doenças Neurodegenerativas , Doença de Alzheimer/tratamento farmacológico , Animais , Produtos Biológicos/farmacologia , Físico-Química , Colestanos , Colestanóis , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Espermina/análogos & derivados
19.
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
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