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1.
Planta Med ; 86(11): 767-775, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32512614

RESUMO

Sweet potato is a functional food with potential antitumor properties, but the bioactive constituents and biological mechanisms remain unclear. In this study, we investigated the antitumor effect of daucosterol linolenate extracted from sweet potato and its potential mechanism. An MTT assay indicated that DLA inhibited the proliferation of breast cancer MCF-7 cells but had only weak effects on the proliferation of MDA-MB-231, 4T1, and MCF-10A cells. Flow cytometry analysis revealed that daucosterol linolenate induced apoptosis of MCF-7 cells. Experiments with MCF-7 xenograft in nude mice further confirmed that DLA inhibited tumor growth dose-dependently. After DLA treatment, the expressions of B-cell lymphoma 2 and vascular endothelial growth factor were decreased and that of cleaved caspase 3 was increased as compared to the TC group. DLA also down-regulated the expression of phosphoinositide 3-kinase/protein kinase B and repressed insulin-induced phosphoinositide 3-kinase/protein kinase B activation. Our findings suggest that DLA suppresses breast tumor growth through inactivating the phosphoinositide 3-kinase/protein kinase B pathway.


Assuntos
Neoplasias da Mama , Ipomoea batatas , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Xenoenxertos , Humanos , Células MCF-7 , Camundongos , Camundongos Nus , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Sitosteroides , Fator A de Crescimento do Endotélio Vascular , Ensaios Antitumorais Modelo de Xenoenxerto , Ácido alfa-Linoleico
2.
Poult Sci ; 99(3): 1400-1408, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32111314

RESUMO

This research investigated effects of dietary ß-sitosterol addition at different levels on serum lipid levels, immune function, oxidative status, and intestinal morphology in broilers. One-day-old broiler chicks were allocated to 5 groups of 6 replicates. Chickens in the 5 groups were fed a basal diet supplemented with 0 (control group), 40, 60, 80, and 100 mg/kg of ß-sitosterol for 42 D, respectively. ß-Sitosterol linearly decreased (P < 0.05) concentrations of serum total cholesterol, jejunal tumor necrosis factor α (TNF-α), and ileal interleukin 1ß (IL-1ß) and mRNA relative expressions levels of jejunal TLR4 and ileal MyD88, whereas it linearly increased (P < 0.05) contents of jejunal immunoglobulin G (IgG), ileal secreted IgA and glutathione, jejunal catalase activity and Nrf2 mRNA relative expression level, villus height (VH), and VH-to-crypt depth (CD) ratio (VH:CD) in the jejunum and ileum. Linear and quadratic increases (P < 0.05) in absolute and relative spleen weight were observed by dietary ß-sitosterol, whereas malondialdehyde (MDA) concentration in the jejunum and ileum followed the opposite trend (P < 0.05). Compared with the control group, dietary ß-sitosterol at higher than or equal to 60 mg/kg level decreased (P < 0.05) contents of serum total cholesterol, ileal MDA, and jejunal TLR4 mRNA relative expression level, whereas it increased (P < 0.05) absolute spleen weight and ileal glutathione content. Higher than or equal to 80 mg/kg level of ß-sitosterol enhanced (P < 0.05) jejunal IgG concentration, VH, catalase activity, and Nrf2 relative expression level and ileal secreted IgA content, but reduced (P < 0.05) ileal IL-1ß content and MyD88 mRNA relative expression level. ß-Sitosterol addition at 60 and 80 mg/kg levels increased (P < 0.05) relative spleen weight, whereas it decreased (P < 0.05) jejunal MDA accumulation. Moreover, 100 mg/kg level of ß-sitosterol reduced (P < 0.05) jejunal TNF-α level, but it increased (P < 0.05) VH in the jejunum and VH:CD in the jejunum and ileum. Accordingly, dietary ß-sitosterol supplementation could regulate serum cholesterol level, promote immune function, and improve intestinal oxidative status and morphology in broilers.


Assuntos
Galinhas/fisiologia , Imunidade Inata/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Lipídeos/sangue , Estresse Oxidativo/efeitos dos fármacos , Sitosteroides/metabolismo , Ração Animal/análise , Animais , Galinhas/sangue , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Intestinos/anatomia & histologia , Distribuição Aleatória , Sitosteroides/administração & dosagem
3.
Food Chem ; 315: 126217, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32007812

RESUMO

This study investigated the direct citric acid hydrolysis extraction method to optimize phytosterols extraction from hickory husk. Single factor experiments followed by a three-level three-factor Box-Behnken experiments were performed. The optimal extraction parameters were determined as: pH of 2.0, liquid-to-solid ratio of 17.12: 1 mL/g, and temperature of 55.81 °C. Practical experiments were carried out in triplicate, and subsequently yielded phytosterols of 912.452 ± 17.452 µg/g DW, in good consistence with the predicted extraction yield of 902.874 µg/g DW. The conductivity of the extract was also found to play effective role under direct citric acid hydrolysis and recorded 36.30 ± 1.08 µs/cm at optimum extraction condition. ß-Sitosterol stigmasterol, campsterol, ergosterol and lupeol were detected as main PSs and triterpenoids in hickory husk using UPLC-Triple-TOF/MS. Finally, the comparison between direct hydrolysis extraction and traditional solvent extraction showed that this new method was more effective and eco-friendlier to extract both free and conjugated phytosterols.


Assuntos
Carya/química , Modelos Teóricos , Fitosteróis/isolamento & purificação , Triterpenos/isolamento & purificação , Ácido Cítrico/química , Ergosterol/química , Ergosterol/isolamento & purificação , Concentração de Íons de Hidrogênio , Hidrólise , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Fitosteróis/química , Sitosteroides/química , Sitosteroides/isolamento & purificação , Estigmasterol/química , Estigmasterol/isolamento & purificação , Triterpenos/química
4.
Nat Commun ; 11(1): 983, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080183

RESUMO

Endosomal sequestration of lipid-based nanoparticles (LNPs) remains a formidable barrier to delivery. Herein, structure-activity analysis of cholesterol analogues reveals that incorporation of C-24 alkyl phytosterols into LNPs (eLNPs) enhances gene transfection and the length of alkyl tail, flexibility of sterol ring and polarity due to -OH group is required to maintain high transfection. Cryo-TEM displays a polyhedral shape for eLNPs compared to spherical LNPs, while x-ray scattering shows little disparity in internal structure. eLNPs exhibit higher cellular uptake and retention, potentially leading to a steady release from the endosomes over time. 3D single-particle tracking shows enhanced intracellular diffusivity of eLNPs relative to LNPs, suggesting eLNP traffic to productive pathways for escape. Our findings show the importance of cholesterol in subcellular transport of LNPs carrying mRNA and emphasize the need for greater insights into surface composition and structural properties of nanoparticles, and their subcellular interactions which enable designs to improve endosomal escape.


Assuntos
Colesterol/análogos & derivados , Lipídeos/química , Nanopartículas/química , RNA Mensageiro/administração & dosagem , Animais , Transporte Biológico Ativo , Linhagem Celular , Colesterol/química , Microscopia Crioeletrônica , Endossomos/metabolismo , Células HEK293 , Células HeLa , Humanos , Camundongos , Nanopartículas/ultraestrutura , Células RAW 264.7 , RNA Mensageiro/genética , Sitosteroides/química , Transfecção , Difração de Raios X
5.
Food Chem ; 314: 126146, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31954944

RESUMO

Sunflower oil enriched with curcuminoid compounds (CUs) was gelled by adding 5% (w/w) saturated monoglycerides (MG), rice bran waxes (RW) or a mixture of ß-sitosterol and γ-oryzanol (PS). The resulting oleogels differed for rheological properties and firmness due to the difference in gel network structure. PS oleogel was the firmest sample followed by RW and MG ones. Upon in vitro digestion, fatty acid release as a function of digestion time was greatly affected by oleogel structure: the extent of lipolysis decreased as oleogel strength increased (PS < RW < MG). On the other hand, the nature of the oleogelator affected CUs bioaccessibility, which was lower in oleogels containing crystalline particles (MG and RW). These findings appear interesting in the attempt to develop oleogels able to control lipid digestion as well as to deliver bioactive molecules in food systems.


Assuntos
Diarileptanoides/farmacocinética , Lipólise , Óleo de Girassol/farmacocinética , Disponibilidade Biológica , Diarileptanoides/química , Digestão , Ácidos Graxos/farmacocinética , Humanos , Monoglicerídeos/química , Compostos Orgânicos/química , Compostos Orgânicos/farmacocinética , Tamanho da Partícula , Fenilpropionatos/química , Reologia , Sitosteroides/química , Óleo de Girassol/química
6.
Food Chem ; 311: 125890, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31757493

RESUMO

The recovery of α-tocopherol and ß-sitosterol from the deodorizer distillate of sunflower oil using solid phase extraction is reported. Performance of the silicon-rich and inexpensive zeolite, ZSM-5, and its modified versions were compared as adsorbents. Modifications of the zeolite frame were performed under both acidic and basic conditions to desilicate and dealuminate the parent ZSM-5. Base treatment resulted in hierarchical porosity and increased mesoporosity in the structure, which made the desilicated material as the best adsorbent of the study. Optimization of the solid phase extraction conditions was also studied and high recoveries of α-tocopherol and ß-sitosterol, up to 99.20% and 97.32%, respectively, were achieved. The preparation and characterisation of the reported sorbents, as high-performance adsorbents, were not only proved to be economically promising, due to recycling of nutritious products, but also improves the ecological credentials of the process through reduction in waste.


Assuntos
Sitosteroides/isolamento & purificação , Óleo de Girassol/química , Zeolitas/química , alfa-Tocoferol/isolamento & purificação , Adsorção , Cromatografia Líquida de Alta Pressão , Porosidade , Sitosteroides/análise , Extração em Fase Sólida , alfa-Tocoferol/análise
7.
Pest Manag Sci ; 76(2): 704-711, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31347760

RESUMO

BACKGROUND: ß-Sitosterol is a plant metabolite with a broad range of anti-fungal activity, however, this compound is not toxic against a few fungal species. The target of ß-sitosterol and the nature of its selective toxicity are not yet clear. Using a yeast model system and taking advantage of molecular biology and computational approaches, we identify the target and explain why ß-sitosterol is not toxic against some fungal pathogens. RESULTS: ß-Sitosterol (200 µg mL-1 ) is toxic against yeast cells expressing only Osh4 (an oxysterol-binding protein) and harbouring a upc2-1 mutation (which enables sterol uptake), but not against yeast strains expressing all seven Osh proteins and harbouring a upc2-1 mutation. Furthermore, ß-sitosterol is not toxic against yeast strains without the upc2-1 mutation irrespective of the number of Osh proteins being expressed. The deletion of COQ1 (a gene known to be highly induced upon deletion of OSH4) enhances the toxicity of ß-sitosterol in yeast cells expressing only Osh4 and harbouring the upc2-1 mutation. Molecular modelling suggests that ß-sitosterol binds to Osh4 and the binding mode is similar to the binding of cholesterol to Osh4. CONCLUSION: Our results indicate that the concentrations of ß-sitosterol, and Osh4, as well as its homologues within cells, are most likely the main determinants of ß-sitosterol toxicity. Furthermore, some fungal species do not take up sterols, e.g. Saccharomyces cerevisiae, under aerobic conditions. Therefore, sterol uptake may also contribute to the ß-sitosterol anti-fungal effect. These findings enable predicting the toxicity of ß-sitosterol against plant fungal pathogens. © 2019 Society of Chemical Industry.


Assuntos
Saccharomyces cerevisiae , Oxisteróis , Proteínas de Saccharomyces cerevisiae , Sitosteroides
8.
Nat Prod Res ; 34(3): 421-424, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30499332

RESUMO

Phytochemical investigation of the Jurinea macrocephala roots afforded six compounds namely ß-sitosterol (1), lupenone (2), physcion (3), ptiloepoxide (4), 20, 21α-epoxytaraxastan-3ß-ol (5) and chlorogenic acid (6). All the compounds were isolated for the first time in roots. The structures of the compounds were established by analysis of their spectroscopic (1H and 13C NMR) and spectrometric (MS) data, as well as by comparison of these with those reported in the literature. Metabolic profiling of chloroform and ethyl acetate fractions were also accomplished using NMR. In NMR analysis, ERETIC (electronic reference to access in-vivo concentration) 2 method was used for the quantification of identified metabolites. High quantity of chlorogenic acid (6, 130 mg/g) lupenone (2, 33.4 mg/g) and amyrins (α, ß) (170.6 mg/g) were detected in ethyl acetate and chloroform fractions. Further studies on the biological evaluation of phenolic-rich and chloroform fractions could be beneficial to explore its pharmaceutical potential.


Assuntos
Asteraceae/química , Compostos Fitoquímicos/análise , Extratos Vegetais/química , Raízes de Plantas/química , Ácido Clorogênico/análise , Estrutura Molecular , Triterpenos Pentacíclicos/análise , Compostos Fitoquímicos/isolamento & purificação , Sitosteroides/análise , Análise Espectral , Triterpenos/análise
9.
Nat Prod Res ; 34(2): 296-299, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30406669

RESUMO

Tephrosia apollinea is a legume species, native to southwest Asia and northeast Africa, rich in bioactive flavonoids (hydrophilic compounds). T. apollinea seeds were not considered previously as a potential source of lipophilic compounds such as: essential fatty acids, tocopherols, sterols, and squalene, hence, the present study were performed. The oil yield in T. apollinea seeds amounted to 11.8% dw. The T. apollinea seed oil was predominated by the polyunsaturated fatty acids - linoleic (26.8%) and α-linolenic (22.7%). High levels were recorded also for oleic (27.6%) and palmitic (14.9%) acids. Four tocopherols and one tocotrienol, with the domination of γ-tocopherol (98%) were identified in T. apollinea seed oil. The ß-sitosterol (59%), Δ5-stigmasterol (21%) and campesterol (9%) were detected as main sterols in T. apollinea seed oil. The total content of tocochromanols, sterols, carotenoids and squalene in the T. apollinea seed oil was 256.7, 338.1, 12.5 and 1103.8 mg/100 g oil, respectively. T. apollinea seeds oil, due to the high concentration of lipophilic bioactive compounds can find a potential application in the food, cosmetic and pharmaceutical industry.


Assuntos
Ácidos Graxos Insaturados/análise , Sementes/química , Esqualeno/isolamento & purificação , Esteróis/isolamento & purificação , Tephrosia/química , Tocoferóis/isolamento & purificação , Carotenoides/análise , Colesterol/análogos & derivados , Fitosteróis , Óleos Vegetais/química , Sitosteroides , Esqualeno/análise , Esteróis/análise , Tocoferóis/análise , Tocotrienóis
10.
J Ethnopharmacol ; 247: 112251, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31560992

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Crateva adansonii DC (Capparaceae) is a shrub used to treat tumors in Cameroon. In our previous reports, a Crateva adansonii dichloromethane-methanol (DCM/MeOH) extract was shown to prevent chemically induced tumors in Wistar rats. AIM OF STUDY: To determine the bioactive principle of Crateva adansonii extract and to elucidate its underlying mechanism. MATERIALS AND METHODS: An activity-guided fractionation was realized using MTT assay. To investigate if the bioactive compound daucosterol (CA2) accounted for the previously observed anticancer effects of the C. adansonii extract, it was tested on cell growth, cell proliferation, cell cycle, cell death mechanism and cell migration. In addition, cell cycle- and apoptosis-regulating proteins were assessed by Western blotting. RESULTS: Daucosterol (CA2), a steroid saponin, was identified as major anticancer principle of the C. adansonii extract. Daucosterol significantly inhibited LNCaP, DU145 and PC3 prostate carcinoma cell growth and proliferation at the optimal concentration of 1 µg/mL. It also significantly increased the number of late apoptotic (DU145) and apoptotic (PC3) cells. The number of cells in S phase increased in DU145, while the number of G0/G1 cells decreased. Cell cycle proteins (cdk1, pcdk1, cyclin A and B) were down-regulated in DU145 and PC3 cells, whereas only cdk2 was down-regulated in PC3 cells. Moreover, the anti-apoptotic Akt, pAKT and Bcl-2 proteins were down-regulated, while the pro-apoptotic protein Bax was up-regulated. CA2 induced anti-metastatic effects by decreasing chemotaxis and cell migration, while it increased cell adhesion to fibronectin and collagen matrix. CONCLUSION: These results suggest that daucosterol is the major active principle responsible at least in part for the anticancer effect of the extract of Crateva adansonii.


Assuntos
Capparaceae/química , Extratos Vegetais/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Sitosteroides/farmacologia , Apoptose/efeitos dos fármacos , Bioensaio , Camarões , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fracionamento Químico , Quimiotaxia/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Medicina Tradicional Africana/métodos , Invasividade Neoplásica/prevenção & controle , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sitosteroides/isolamento & purificação , Regulação para Cima/efeitos dos fármacos
11.
Food Chem Toxicol ; 136: 111036, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862287

RESUMO

Maqui-berry (Aristotelia chilensis) is the emerging Chilean superfruit with high nutraceutical value. Until now, the research on this commodity was focused on the formulations enriched with polyphenols from the pulp. Herein, contents of tocols were compared in the seed oil of Maqui-berry obtained through three different extraction methods followed by determining their antioxidative and enzyme inhibitions in-vitro. Firstly, oilseed was extracted with n-hexane (Soxhlet method), chloroform/methanol/water (Bligh and Dyer method) and pressing (industrial). These samples were used to access their effects against DPPH, HORAC, ORAC, FRAP, Lipid-peroxidation (TBARS), α-amylase, α-glucosidase, and pancreatic lipase. All the isomers of tocopherol and tocotrienol were identified, and ß-sitosterol was the only sterol found in higher amounts than other vegetable oils. The Bligh and Dyer method could lead to the highest antioxidative capacity compared to Soxhlet and press methods likely because the latter have a higher amount of tocopherols. Further, seed oil from Maqui berry and their tocols (α, ß, γ, δ-tocopherols, tocotrienols, and ß-sitosterol) warrant clinical investigation for their antioxidative and antiobesity potential. Taken together, these findings provide relevant and suitable conditions for the industrial processing of Maqui-berry.


Assuntos
Fármacos Antiobesidade/farmacologia , Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Sitosteroides/farmacologia , Tocoferóis/farmacologia , Tocotrienóis/farmacologia , Animais , Fármacos Antiobesidade/análise , Antioxidantes/análise , Inibidores Enzimáticos/análise , Lipase/antagonistas & inibidores , Magnoliopsida/química , Masculino , Ratos Wistar , Sementes/química , Sitosteroides/análise , Tocoferóis/análise , Tocotrienóis/análise
12.
An Acad Bras Cienc ; 91(4): e20181088, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800700

RESUMO

Aged skin, featured with dryness and wrinkles, has received mounting attention due to its adverse influences on beauty. ß-Sitosterol and vermicularin are two common active ingredients of Thamnolia vermicularis (Sw.) Ach., a traditional Chinese medicine, of which the anti-aging effect has been discovered. Their protective performance against skin aging was assayed by co-culturing with skin cells in this work. Results showed that ß-sitosterol promoted the biosynthesis of hyaluronic acid by increasing the expression of hyaluronic acid synthases in fibroblasts and enhanced the expression of skin barrier functional proteins including aquaporin 3, loricrin, filaggrin and involucrin in keratinocytes, which conduced to the moisture retention within skin. Moreover, vermicularin might function as an anti-wrinkle agent by preventing the loss of collagen type I. Specifically, vermicularin reduced the amount of reactive oxygen species within hydrogen-peroxide-induced fibroblasts; together with suppressing the activation of mitogen-activated protein kinases, it could inhibit the production of matrix metalloproteinases-1. The present research will contribute to the development of the compounds as anti-aging ingredients for future applications in cosmetic formulations and functional food as well as promote further studies of raw materials containing alike compounds.


Assuntos
Fibroblastos/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sitosteroides/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Linhagem Celular , Humanos , Substâncias Protetoras/farmacologia
13.
Molecules ; 24(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683500

RESUMO

ß-sitosterol ß-d-glucoside (BSSG) was extracted from "piña" of the Agave angustifolia Haw plant by microwave-assisted extraction (MAE) with a KOH solution such as a catalyst and a conventional maceration method to determine the best technique in terms of yield, extraction time, and recovery. The quantification and characterization of BSSG were done by high-performance thin layer chromatography (HPTLC), Fourier-transform infrared spectroscopy (FT-IR), and high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS). With an extraction time of 5 s by MAE, a higher amount of BSSG (124.76 mg of ß-sitosterol ß-d-glucoside/g dry weight of the extract) than those for MAE extraction times of 10 and 15 s (106.19 and 103.97 mg/g dry weight respectively) was shown. The quantification of BSSG in the extract obtained by 48 h of conventional maceration was about 4-5 times less (26.67 mg/g dry weight of the extract) than the yields reached by the MAE treatments. MAE achieved the highest amount of BSSG, in the shortest extraction time while preserving the integrity of the compound's structure.


Assuntos
Agave/química , Etanol/química , Micro-Ondas , Extratos Vegetais/química , Sitosteroides/análise , Cromatografia em Camada Delgada , Padrões de Referência , Sitosteroides/química , Soluções , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier
14.
Cardiovasc Diabetol ; 18(1): 158, 2019 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733647

RESUMO

BACKGROUND: Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain. AIM AND METHODS: We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared with those of sitagliptin. The study was a secondary analysis using data obtained from the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. This trial in patients with type 2 diabetes at a high risk of cardiovascular events and on statin therapy showed that anagliptin reduced LDL-C levels to a greater extent than sitagliptin. Cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) markers were measured at baseline and 52 weeks in the study cohort (n = 353). RESULTS: There was no significant difference in the changes of campesterol or sitosterol between the two treatment groups (p = 0.85 and 0.55, respectively). Lathosterol concentration was increased significantly at 52 weeks with sitagliptin treatment (baseline, 1.2 ± 0.7 µg/mL vs. 52 weeks, 1.4 ± 1.0 µg/mL, p = 0.02), whereas it did not change in the anagliptin group (baseline, 1.3 ± 0.8 µg/mL vs. 52 weeks, 1.3 ± 0.7 µg/mL, p = 0.99). The difference in absolute change between the two groups showed a borderline significance (p = 0.06). CONCLUSION: These findings suggest that anagliptin reduces LDL-C level by suppressing excess cholesterol synthesis, even in combination with statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. https://clinicaltrials.gov/ct2/show/NCT02330406; registered January 5, 2015.


Assuntos
LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirimidinas/uso terapêutico , Fosfato de Sitagliptina/uso terapêutico , Idoso , Biomarcadores/sangue , Colesterol/análogos & derivados , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Japão , Masculino , Pessoa de Meia-Idade , Fitosteróis/sangue , Pirimidinas/efeitos adversos , Fosfato de Sitagliptina/efeitos adversos , Sitosteroides/sangue , Fatores de Tempo , Resultado do Tratamento
15.
J Agric Food Chem ; 67(45): 12461-12471, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31613618

RESUMO

In this study, derivatization of epigallocatechin (EGC) by representative phytosterols (stigmasterol and ß-sitosterol) was performed employing Steglich esterification. The structural identity and purity of epigallocatechin ß-sitosterol (ESi) and epigallocatechin stigmasterol (ESt) were confirmed by NMR, FT-IR, and HPLC-MS. Further evaluation of ESi and ESt revealed their extraordinary antioxidant activities in O/W emulsion. Two different radical sources in oil or aqueous phase were applied to explore the antioxidant behavior in O/W emulsion. The mechanism was further investigated by fluorescent microscopy and transmission electron microscopy (TEM). Furthermore, incorporation of EGC with stigmasterol and ß-sitosterol notably enhanced the cholesterol-reducing activity. TEM studies suggested the hydrogen bonding of EGC strengthened the aggregation network of ESi and ESt in the bile salt micelle. The exceptional properties of ESi and ESt signified their intriguing utilization in the food industry.


Assuntos
Antioxidantes/química , Catequina/análogos & derivados , Colesterol/química , Fitosteróis/química , Catequina/química , Emulsões/química , Esterificação , Oxirredução , Sitosteroides/química , Estigmasterol/química
16.
Lipids Health Dis ; 18(1): 185, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653257

RESUMO

BACKGROUND: Cholesterol is an essential component in human development. In fetuses affected by intrauterine growth restriction (IUGR), fetal blood cholesterol levels are low. Whether this is the result of a reduced materno-fetal cholesterol transport, or due to low fetal de novo synthesis rates, remains a matter of debate. By analyzing cholesterol interbolites and plant sterols we aimed at deeper insights into transplacental cholesterol transport and fetal cholesterol handling in IUGR with potential targets for future therapy. We hypothesized that placental insufficiency results in a diminished cholesterol supply to the fetus. METHODS: Venous umbilical cord sera were sampled post-partum from fetuses delivered between 24 weeks of gestation and at full term. IUGR fetuses were matched to 49 adequate-for-age delivered preterm and term neonates (CTRL) according to gestational age at delivery. Cholesterol was measured by gas chromatography-flame ionization detection using 5a-cholestane as internal standard. Cholesterol precursors and synthesis markers, such as lanosterol, lathosterol, and desmosterol, the absorption markers, 5α-cholestanol and plant sterols, such as campesterol and sitosterol, as well as enzymatically oxidized cholesterol metabolites (oxysterols), such as 24S- or 27-hydroxycholesterol, were analyzed by gas chromatography-mass spectrometry, using epicoprostanol as internal standard for the non-cholesterol sterols and deuterium labeled oxysterols for 24S- and 27-hydroxycholesterol. RESULTS: Mean cholesterol levels were 25% lower in IUGR compared with CTRL (p < 0.0001). Lanosterol and lathosterol to cholesterol ratios were similar in IUGR and CTRL. In relation to cholesterol mean, desmosterol, 24S-hydroxycholesterol, and 27-hydroxycholesterol levels were higher by 30.0, 39.1 and 60.7%, respectively, in IUGR compared to CTRL (p < 0.0001). Equally, 5α-cholestanol, campesterol, and ß-sitosterol to cholesterol ratios were higher in IUGR than in CTRL (17.2%, p < 0.004; 33.5%, p < 0.002; 29.3%, p < 0.021). CONCLUSIONS: Cholesterol deficiency in IUGR is the result of diminished fetal de novo synthesis rates rather than diminished maternal supply. However, increased oxysterol- and phytosterol to cholesterol ratios suggest a lower sterol elimination rate. This is likely caused by a restricted hepatobiliary function. Understanding the fetal cholesterol metabolism is important, not only for neonatal nutrition, but also for the development of strategies to reduce the known risk of future cardiovascular diseases in the IUGR fetus.


Assuntos
Sangue Fetal/metabolismo , Retardo do Crescimento Fetal/sangue , Adulto , Colesterol/análogos & derivados , Colesterol/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hidroxicolesteróis/sangue , Recém-Nascido , Fitosteróis/sangue , Placenta/metabolismo , Gravidez , Sitosteroides/sangue
17.
BMC Complement Altern Med ; 19(1): 270, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623582

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is a pathological condition affecting older men. BPH complications often lead to deterioration in the quality of life. Serenoa repens (Saw Palmetto) is used for treating lower urinary tract infections in traditional medicine. METHODS: This study was performed to compare the efficacy of ß-sitosterol enriched saw palmetto oil (VISPO) and conventional saw palmetto oil (SPO) extracted using supercritical fluid extraction, in alleviating the BPH complications using testosterone-induced BPH model rats. The animals received testosterone (5 mg/kg s.c.) with or without SPO and VISPO (200 and 400 mg/kg b.w.) or Finasteride (1 mg/kg b.w.) p.o. for 28 days. At the end of the experiment, overnight fasted animals were euthanized, blood samples collected for serum analysis of testosterone. Prostate tissue histomorphology was examined by hematoxylin and eosin (H&E) staining. Western blot analysis was performed using prostate tissue homogenates. RESULTS: VISPO exhibited superior efficacy compared to SPO as evident from the significant decrease in prostate weight to body weight ratio, serum testosterone level and increase in growth inhibition of prostate tissue compared to BPH group (p < 0.001). Histological examination of prostate tissue samples showed that VISPO treatment was comparatively better than SPO in improving the hyperplastic patterns. Further, VISPO significantly regulated the expression of inflammatory and apoptotic marker proteins in BPH rats. CONCLUSION: Our data provide experimental evidence that ß-sitosterol enriched saw palmetto oil could be higher efficacious in treating the BPH complications compared to the conventional saw palmetto oil preparations.


Assuntos
Fitosteróis/administração & dosagem , Extratos Vegetais/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Animais , Cromatografia com Fluido Supercrítico , Humanos , Masculino , Fitosteróis/isolamento & purificação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Próstata/efeitos dos fármacos , Próstata/imunologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Ratos , Ratos Wistar , Serenoa/química , Sitosteroides/administração & dosagem , Sitosteroides/isolamento & purificação , Testosterona/efeitos adversos , Testosterona/sangue , Proteína X Associada a bcl-2/imunologia
18.
J Plant Res ; 132(6): 881-901, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31606785

RESUMO

Water stress reduces crop production significantly, and climate change has further aggravated the problem mainly in arid and semi-arid regions. This was the first study on the possible effects of ß-sitosterol application in ameliorating the deleterious changes in wheat induced by water stress under field condition and drip irrigation regimes. A field experiment with the split-plot design was conducted, and wheat plants were foliar sprayed with four ß-sitosterol (BBS) concentrations (0, 25, 75, and 100 mg L-1) and two irrigation regimes [50 and 100% of crop evapotranspiration (ETc)]. Water stress without BBS treatment reduced biological yield, grain yield, harvest index, and photosynthetic efficiency significantly by 28.9%, 42.8%, 19.6%, and 20.5% compared with the well-watered plants, respectively. Proline content increased in water-stressed and BSS-treated plants, owing to a significant role in cellular osmotic adjustment. Application of BSS was effective in reducing the generation of hydrogen peroxide (H2O2) and hence the malondialdehyde content significantly in water-stressed and well-watered wheat plants. Application of BSS up-regulated the activity of antioxidant enzymes (SOD, CAT, POD, and APX) significantly and increased the content of tocopherol, ascorbic acid, and carotene thereby reducing the levels of reactive oxygen species. The increased antioxidant system in BSS treated plants was further supported by the expression level of SOD and dehydrin genes in both water-stressed and well-watered plants. In the present study, the application of BBS at 100 mg L-1 was beneficial and can be recommended for improving the growth and yield of the wheat crop under water stress.


Assuntos
Antioxidantes/metabolismo , Secas , Substâncias Protetoras/administração & dosagem , Sitosteroides/administração & dosagem , Triticum/fisiologia , Relação Dose-Resposta a Droga , Distribuição Aleatória , Triticum/efeitos dos fármacos , Triticum/crescimento & desenvolvimento , Regulação para Cima/efeitos dos fármacos
19.
Molecules ; 24(19)2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31546651

RESUMO

Hechtia glomerata Zucc. is used both as a source of food and in ethnomedicine to treat various diseases derived from bacterial infections such as bronchitis, laryngitis, nephritis, whooping cough, urethritis, and sepsis. There are no previous reports about its chemistry and biological activities. Therefore, the aims of this study were to identify components from organic and aqueous extracts of H. glomerata and test the extracts and major isolate compounds against resistant bacteria. Hexane, CHCl3/MeOH, and aqueous extracts were prepared and analyzed by different chromatographic techniques. Structural elucidation was carried out by NMR spectroscopy and X-ray diffraction. The antibacterial activities of extracts, phytochemicals, and semisynthetic derivatives against resistant bacteria were determined by the broth micro-dilution method. From the hexane extract nonacosane (1), hexatriacontanyl stearate (2), hexacosanol (3), oleic acid (4), and ß-sitosterol (5) were isolated and characterized. From the CHCl3/MeOH extract, p-coumaric acid (6), margaric acid (7), caffeic acid (8), daucosterol (9), and potassium chloride (10) were isolated and characterized. A total of 58 volatile compounds were identified by GC-MS from the hexane extract and two solids were isolated from the CHCl3/MeOH extract. The UPLC-QTOF-MS analysis of the aqueous extract allowed the identification of 55 polar compounds. Hexane and aqueous extracts showed antibacterial activity against ESBL Escherichia coli, and three strains of Klebsiella pneumoniae ESBL, NDM-1 +, and OXA-48 with MIC values of 500 µg/mL. The CHCl3/MeOH extract was devoid of activity. The activity of phytocompounds and their semisynthetic derivatives toward resistant bacteria was weak. The most active compound was ß-sitosterol acetate, with a MIC value of 100 µg/mL against carbapenem-resistant A. baumannii. This is the first report of the secondary metabolites of H. glomerata Zucc. and the activity of its extracts and major pure compounds against resistant bacterial strains.


Assuntos
Bactérias/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Alcanos/química , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Medicina Tradicional , Testes de Sensibilidade Microbiana , Ácido Oleico/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Sitosteroides/química
20.
Planta ; 250(6): 2033-2046, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542810

RESUMO

MAIN CONCLUSION: ß-sitosterol influences amino acids, carbohydrates, organic acids, and other metabolite metabolism and homeostasis largely contributing to better tolerance to water stress in white clover. ß-sitosterol (BS) could act as an important plant growth regulator when plants are subjected to harsh environmental conditions. Objective of this study was to examine effects of BS on growth and water stress tolerance in white clover based on physiological responses and metabolomics. White clover was pretreated with or without BS and then subjected to water stress for 7 days in controlled growth chambers. Physiological analysis demonstrated that exogenous application of BS (120 µM) could significantly improve stress tolerance associated with better growth performance and photosynthesis, higher leaf relative water content, and less oxidative damage in white clover in response to water stress. Metabolic profiling identified 78 core metabolites involved in amino acids, organic acids, sugars, sugar alcohols, and other metabolites in leaves of white clover. For sugars and sugar alcohol metabolism, the BS treatment enhanced the accumulation of fructose, glucose, maltose, and myo-inositol contributing to better antioxidant capacity, growth maintenance, and osmotic adjustment in white clover under water stress. The application of BS was inclined to convert glutamic acid into proline, 5-oxoproline, and chlorophyll instead of going to pyruvate and alanine; the BS treatment did not significantly affect intermediates of tricarboxylic acid cycle (citrate, aconitate, and malate), but promoted the accumulation of other organic acids including lactic acid, glycolic acid, glyceric acid, shikimic acid, galacturonic acid, and quinic acid in white clover subjected to water stress. In addition, cysteine, an important antioxidant metabolite, was also significantly improved by BS in white clover under water stress. These altered amino acids and organic acids metabolism could play important roles in growth maintenance and modulation of osmotic and redox balance against water stress in white clover. Current findings provide a new insight into BS-induced metabolic homeostasis related to growth and water stress tolerance in plants.


Assuntos
Reguladores de Crescimento de Planta/fisiologia , Sitosteroides/metabolismo , Trifolium/metabolismo , Membrana Celular/metabolismo , Desidratação , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica , Estresse Oxidativo , Fotossíntese , Reguladores de Crescimento de Planta/metabolismo , Trifolium/crescimento & desenvolvimento , Trifolium/fisiologia
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