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1.
Mediators Inflamm ; 2022: 2222270, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060927

RESUMO

Airway inflammation in asthma is managed with anti-inflammatory steroids such as dexamethasone (DEX). However, about 20% of asthmatics do not respond to this therapy and are classified as steroid-resistant. Currently, no effective therapy is available for steroid-resistant asthma. This work therefore evaluated the effect of a plant sterol, stigmasterol (STIG), and stigmasterol-dexamethasone combination (STIG+DEX) in LPS-ovalbumin-induced steroid-resistant asthma in Guinea pigs. To do this, the effect of drugs on inflammatory features such as airway hyperreactivity and histopathology of lung tissue was evaluated. Additionally, the possible pathway of drug action was assessed by measuring events such neutrophil levels, oxidative and nitrative stress, and histone deacetylase 2 (HDAC2) and interleukin 17 (IL-17) levels. STIG alone did not affect inflammatory features, although it caused some changes in the molecular events associated with steroid-resistant asthma. However, STIG+DEX caused significant modulation of inflammatory features by protecting against destruction of lung tissue. The modulation of inflammatory features was associated with significant inhibition of neutrophilia and oxidative and nitrative stress, decrease in HDAC2, and increase in IL-17 levels that are usually associated with steroid-resistant asthma. Our findings show that although STIG and DEX individually do not protect against steroid-resistant asthma, their coadministration results in significant modulation of inflammatory features and the associated molecular events that lead to steroid-resistant asthma.


Assuntos
Asma , Estigmasterol , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Dexametasona/uso terapêutico , Resistência a Medicamentos , Cobaias , Interleucina-17/uso terapêutico , Esteroides/farmacologia
2.
Int J Mol Sci ; 23(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35955570

RESUMO

Cotton is an important economic crop. Cotton Verticillium wilt caused by Verticillium dahliae seriously damages production. Phytosterols play roles in plant-pathogen interaction. To explore the function and related mechanism of phytosterols in the interaction between Verticillium dahliae and cotton plants, and the resistance to Verticillium wilt, in this study, we analyzed the changes of sterol composition and content in cotton roots infected by Verticillium dahliae, and identified the sterol C22-desaturase gene GhCYP710A1 from upland cotton. Through overexpressing and silencing the gene in cotton plant, and ectopically expressing the gene in Arabidopsis, we characterized the changes of sterol composition and the resistance to Verticillium wilt in transgenic plants. The infection of Verticillium dahliae resulted in the content of total sterol and each sterol category decreasing in cotton root. The ratio of stigmasterol to sitosterol (St/Si) increased, indicating that the conversion of sitosterol to stigmasterol was activated. Consistently, the expression level of GhCYP710A1 was upregulated after infection. The GhCYP710A1 has the conservative domain that is essential for sterol C22-desaturase in plant and is highly expressed in root and stem, and its subcellular location is in the endoplasmic reticulum. The ectopic expression of GhCYP710A1 gene promoted the synthesis of stigmasterol in Arabidopsis. The St/Si value is dose-dependent with the expression level of GhCYP710A1 gene. Meanwhile, the resistance to Verticillium wilt of transgenic Arabidopsis increased and the permeability of cell membrane decreased, and the content of ROS decreased after V991 (a strain of Verticillium dahliae) infection. Consistently, the resistance to Verticillium wilt significantly increased in the transgenic cotton plants overexpressing GhCYP710A1. The membrane permeability and the colonization of V991 strain in transgenic roots were decreased. On the contrary, silencing GhCYP710A1 resulted in the resistance to Verticillium wilt being decreased. The membrane permeability and the colonization of V991 were increased in cotton roots. The expression change of GhCYP710A1 and the content alteration of stigmasterol lead to changes in JA signal transduction, hypersensitivity and ROS metabolism in cotton, which might be a cause for regulating the Verticillium wilt resistance of cotton plant. These results indicated that GhCYP710A1 might be a target gene in cotton resistance breeding.


Assuntos
Arabidopsis , Verticillium , Arabidopsis/genética , Arabidopsis/metabolismo , Membrana Celular/metabolismo , Resistência à Doença/genética , Ácidos Graxos Dessaturases/metabolismo , Regulação da Expressão Gênica de Plantas , Gossypium/genética , Gossypium/metabolismo , Melhoramento Vegetal , Doenças das Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sitosteroides , Estigmasterol/farmacologia , Verticillium/fisiologia
3.
Chem Biodivers ; 19(9): e202200495, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35856892

RESUMO

OBJECT: Edible Brown Seaweed Sargassum fusiforme (Harvey) Setchell, 1931 abbreviated as Sargassum fusiforme was used for folk medical therapy in East Asia countries over five hundred years. Saringosterol acetate (SA) was isolated from S. fusiforme in our previous study and indicated various effects. However, anti-obesity activity of SA and its mechanism still unknown. METHOD: The inhibitory effect of SA, isolated from S. fusiforme, on adipogenesis in 3T3-L1 adipocytes was investigated in vitro and in zebrafish model. Cell toxicity, differentiation, signaling pathway, and lipid accumulation of SA treated 3T3-L1 adipocytes were determined. The body weight and triglyceride content of diet-induced obese (DIO) adult male zebrafish were measured from 12 to 17 weeks after fertilization. RESULT: SA attenuated the differentiation of cells and reduced lipid accumulation, and triglyceride content in the 3T3-L1 adipocytes. During the differentiation of adipocytes, SA suppressed fat accumulation and decreased the expression of signal factors responsible for adipogenesis. In SA-treated adipocytes, while fatty acid synthetase was downregulated, AMP-activated protein kinase (AMPK) was upregulated. Furthermore, SA suppressed body weight and triglyceride content in DIO zebrafish. CONCLUSION: SA is a potential therapeutic agent in the management of metabolic disorders, such as obesity.


Assuntos
Proteínas Quinases Ativadas por AMP , Peixe-Zebra , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Acetatos/farmacologia , Adipogenia , Animais , Peso Corporal , Dieta Hiperlipídica , Ácido Graxo Sintases/metabolismo , Ácido Graxo Sintases/farmacologia , Ácido Graxo Sintases/uso terapêutico , Masculino , Camundongos , Obesidade/tratamento farmacológico , Estigmasterol/análogos & derivados , Estigmasterol/farmacologia , Triglicerídeos/metabolismo , Peixe-Zebra/metabolismo
4.
BMC Pharmacol Toxicol ; 23(1): 42, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725497

RESUMO

BACKGROUND: Breast cancer is one of the most common types of cancer in women worldwide. Anti-apoptotic activity of cancer cells is considered the main reason for drug resistance in BC which reduces the 5-year survival rate of patients and is still considered the main obstacle for cancer therapy. Stigmasterol (SS) is natural phytosterols compound in the plant which has been proved to play an important role to lower cholesterol and inducing anti-inflammatory, and anticancer properties. METHODS: In this, study, we aimed to evaluate the effect of SS on the expression of anti-apoptotic genes (Bcl-2 and BCL-XL), and also evaluate its effects on cell apoptosis and cell viability using MCF-7 cell line as well as evaluating its effect on tumor growth of spontaneous breast tumor (SMMT) in vivo. RESULT: SS significantly decreased the expression of Bcl-2 and BCL-XL genes (*P < 0.05), induced apoptosis, and reduced cell proliferation in MCF-7 cell lines. Our in vivo study also indicated that SS could inhibit tumor size after treatment with (0, 10, 20 µM) compared to the normal control. CONCLUSION: SS can be suggested as a potential agent in BC cancer treatment or as an adjuvant based on its ability to decrease the expression of Bcl-2 and BCL-XL genes and induce apoptosis.


Assuntos
Neoplasias da Mama , Estigmasterol , Animais , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Estigmasterol/farmacologia , Estigmasterol/uso terapêutico , Proteína bcl-X/genética , Proteína bcl-X/metabolismo , Proteína bcl-X/farmacologia
5.
Biomed Pharmacother ; 153: 113317, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35772378

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Although its pathogenesis remains unclear, studies have indicated microglia-mediated neuroinflammation playing an important role. Phytosterols are a class of natural compounds presented in food, and have anti-inflammatory abilities. Recent studies suggested that phytosterols can traverse the blood-brain barrier and enter the brain, however, it remains largely unknown that whether phytosterols affect neuroinflammation in the AD pathogenesis. Here, we used APPswe/PS1dE9 mice as the animal model of AD, and found that stigmasterol treatment attenuated cognitive deficits, and decreased Aß42 concentration in cortex and hippocampus. Stigmasterol treatment also suppressed neuroinflammation, by reducing pro-inflammatory cytokine levels and microglia activation. Next, we simulated BV2 cells with Aß42 oligomers, which induced inflammatory responses of microglia. Stigmasterol protected BV2 cells against Aß42 oligomers induced inflammation, and mediated secretion of pro-inflammatory cytokines via NF-κB and NLRP3 signaling pathways by AMPK activation. Stigmasterol also alleviated the M1 polarization of BV2 cells. In general, our study demonstrates that stigmasterol ameliorated neuroinflammation in APP/PS1 mice, and suppressed inflammatory response of microglia to Aß42 oligomers via AMPK/NF-κB and AMPK/NLRP3 signaling, which provides a mechanistic insight for stigmasterol in anti-inflammation and AD therapy.


Assuntos
Doença de Alzheimer , Microglia , Proteínas Quinases Ativadas por AMP/metabolismo , Doença de Alzheimer/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Camundongos , Microglia/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estigmasterol/farmacologia , Estigmasterol/uso terapêutico
6.
Nutrients ; 14(11)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35683987

RESUMO

Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although the symptoms are absent or poorly expressed in most cases, some patients may progress to end-stage liver disease. The pathogenesis of NAFLD is known to be multifactorial. Current therapeutic recommendations focus on lifestyle changes in order to reduce the incidence of risk factors and drugs targeting major molecular pathways potentially involved in the development of this disease. Given that a pharmacological treatment, completely safe and effective, is not currently known in recent years more research has been done on the effects that some bio-active natural compounds, derived from plants, have in preventing the onset and progression of NAFLD. Numerous studies, in animals and humans, have shown that phytosterols (PSs) play an important role in this pathology. Phytosterols are natural products that are found naturally in plant. More than 250 phytosterols have been identified, but the most common in the diet are stigmasterol, ß-sitosterol, and campesterol. Consumption of dietary PSs can reduce serum cholesterol levels. Due to these properties, most studies have focused on their action on lipid metabolism and the evolution of NAFLD. PSs may reduce steatosis, cytotoxicity oxidative stress, inflammation, and apoptosis. The purpose of this review is to provide an overview of the importance of dietary phytosterols, which are a window of opportunity in the therapeutic management of NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Fitosteróis , Animais , Dieta , Humanos , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fitosteróis/farmacologia , Fitosteróis/uso terapêutico , Estigmasterol
7.
Molecules ; 27(11)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35684341

RESUMO

New carriers of phytosterols; acylglycerols containing natural myristic acid at sn-1 and sn-3 positions and stigmasterol residue linked to sn-2 position by carbonate and succinate linker have been designed and synthesized in three-step synthesis from dihydroxyacetone (DHA). The synthetic pathway involved Steglich esterification of DHA with myristic acid; reduction of carbonyl group of 1,3-dimyristoylpropanone and esterification of 1,3-dimyristoylglicerol with stigmasterol chloroformate or stigmasterol hemisuccinate. The structure of the obtained hybrids was established by the spectroscopic methods (NMR; IR; HRMS). Obtained hybrid molecules were used to form new liposomes in the mixture with model phospholipid and their effect on their physicochemical properties was determined, including the polarity, fluidity, and main phase transition of liposomes using differential scanning calorimetry and fluorimetric methods. The results confirm the significant effect of both stigmasterol-containing acylglycerols on the hydrophilic and hydrophobic region of liposome membranes. They significantly increase the order in the polar heads of the lipid bilayer and increase the rigidity in the hydrophobic region. Moreover, the presence of both acylglycerols in the membranes shifts the temperature of the main phase transition towards higher temperatures. Our results indicate stabilization of the bilayer over a wide temperature range (above and below the phase transition temperature), which in addition to the beneficial effects of phytosterols on human health makes them more attractive components of novel lipid nanocarriers compared to cholesterol.


Assuntos
Lipossomos , Fitosteróis , Varredura Diferencial de Calorimetria , Glicerídeos , Humanos , Bicamadas Lipídicas/química , Lipossomos/química , Ácido Mirístico , Fitosteróis/química , Estigmasterol/química
8.
Sci Rep ; 12(1): 9910, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35701649

RESUMO

Many individual herbs and herbal formulae have been demonstrated to provide safe and effective treatment for pancreatic ductal adenocarcinoma (PDAC); however, the therapeutic mechanisms underlying their effects have not been fully elucidated. A total of 114 herbal formulae comprising 216 single herbal medicines used to treat PDAC were identified. Cluster analysis revealed a core prescription including four herbs [Glycyrrhizae Radix et Rhizome (Gan Cao), Codonopsis Radix (Dang Shen), Citri Reticulatae Pericarpium (Chen Pi), and Pinelliae Rhizoma (Ban Xia)] in combination to treat PDAC, and 295, 256, 141, and 365 potential targets were screened for each of these four herbs, respectively. PDAC-related proteins (n = 2940) were identified from the DisGeNET database. Finally, 44 overlapping targets of herbs and PDAC were obtained, representing potential targets of the herbal medicines for PDAC treatment. GO enrichment analysis indicated that targets common to herbs and PDAC primarily functioned in response to steroid hormones. KEGG pathway enrichment analysis indicated that the herbs may prevent PDAC by influencing apoptotic, p53, and PI3K/Akt signaling pathways. Further, molecular docking analysis indicated that of identified bioactive compounds, stigmasterol, phaseol, perlolyrine, shinpterocarpin, and licopyranocoumarin have good binding ability with proteins involved in responses to steroid hormones, while stigmasterol, phaseol, perlolyrine, and DIOP have good binding ability with PTGS2(also known as COX-2), ESR1, ESR2, AR, and PGR. The anti-PDAC activity of herbal medicines may be mediated via regulation of proteins with roles in responses to steroid hormones. This study provides further evidence supporting the potential for use of herbal medicines to treat PDAC.


Assuntos
Adenocarcinoma , Medicamentos de Ervas Chinesas , Plantas Medicinais , Adenocarcinoma/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Hormônios , Humanos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Esteroides , Estigmasterol
9.
Dis Markers ; 2022: 2008556, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493299

RESUMO

The cholesterol metabolism in humans can be indirectly reflected by measuring cholesterol metabolism marker levels. We aimed to investigate the association of cholesterol homeostasis markers on standard lipid profiling components in familial hypercholesteremia and hyperlipidemia patients. A total of 69 hyperlipidemia patients, 25 familial hypercholesteremia (FHC) patients, and 64 healthy controls were enrolled in this study. We performed routine testing of blood lipid water. Gas chromatography was used to determine the changes in the concentration of cholesterol synthesis (squalene, desmosterol, and lathosterol) and absorption markers (campesterol, sitosterol, and stigmasterol) in the blood. Baseline hyperlipidemia patients displayed significantly higher total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels in comparison to the control group, which was reflected in the increased levels of squalene, desmosterol, campesterol, and sitosterol observed (P < 0.05) in the hyperlipidemia patients. The desmosterol, lathosterol, campesterol, stigmasterol, and sitosterol were statistically different in the FHC group than the hyperlipidemic group (P < 0.05). The proportions of squalene/cholesterol, lathosterol/cholesterol, stigmasterol/cholesterol, and sitosterol/cholesterol in the FHC group were lower than those in the hyperlipidemic group; only desmosterol/cholesterol was higher than that in the hyperlipidemic group. Correlation studies between lipid metabolic factors showed that the proportion of moderate and strong correlations was much higher in the FHC group than in the other two groups (76.92% vs. 32.50% and 31.25%). Logistic regression analysis showed that the concentrations of glucose, LDL-C, lactosterol, and sitosterol were all independent risk factors for developing hyperlipidemia. This result was further confirmed by the ROC curve. These results indicated that the study of cholesterol synthesis and decomposition markers can serve as a reference index for related diseases caused by changes in its concentration.


Assuntos
Hipercolesterolemia , Hiperlipidemias , Hiperlipoproteinemia Tipo II , Colesterol , LDL-Colesterol , Desmosterol , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Lipídeos , Sitosteroides , Esqualeno , Estigmasterol
10.
Food Chem ; 390: 133150, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35551028

RESUMO

The study investigated the thermo-oxidative stability of distigmasterol-modified acylglycerols as a new structured acylglycerols. Samples were heated at 60 and 180 °C for 8 h. Their percentage degradation and products formed during heating were compared with free stigmasterol and stigmasteryl esters. The remaining of stigmasterol and fatty acid parts, the formation of stigmasterol oxidation products and the composition of polar and non-polar fractions were analysed using chromatographic methods. The cytotoxicity and genotoxicity were determined with the use of an MTT test and a comet assay, respectively. The highest stability during heating was observed for 2,3-distigmasterylsuccinoyl-1-oleoyl-sn-glycerol (dStigS-OA) and the lowest for 2,3-distigmasterylcarbonoyl-1-oleoyl-sn-glycerol (dStigC-OA). Data showed that the formation of thermo-oxidative degradation products is affected by the temperature and chemical structure of lipids present in the molecule. The dStigMAs bonded by a succinate linker and products formed during their thermo-oxidation showed no cytotoxic or genotoxic activity to normal human cells.


Assuntos
Fitosteróis , Glicerídeos , Glicerol , Humanos , Estresse Oxidativo , Fitosteróis/química , Estigmasterol/química
11.
Metab Brain Dis ; 37(5): 1609-1639, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35366129

RESUMO

Bupleurum chinense DC. (Chaihu) is a traditional Chinese medicine (TCM) used in the treatment of anxiety. But the anxiolytic mechanisms of bupleurum are still unclear. Therefore, this unknown is predicted by network pharmacology study with molecular docking in the present study. The components of bupleurum were obtained from the databases. Genes associated with components and disease were also provided by databases. Overlapping genes between components and disease were analyzed. The network of medicine-components-targets-disease was constructed, visualized, and analyzed. Protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG) and molecular docking were conducted to predict the potential mechanisms of bupleurum on anxiety. A total of 9 bioactive components derived from bupleurum with 80 target genes were involved in anxiety. Neurotransmitter receptor activity, G protein-coupled amine receptor activity, regulation of blood circulation, neuroactive ligand-receptor interaction, calcium signaling pathway and salivary secretion may play significant roles in the anxiolytic of bupleurum. Molecular docking implicated that ACHE and MAOA showed high affinity for stigmasterol. Based on network pharmacology study with molecular docking, multi-component-multi-target-multi-pathway action mode of bupleurum on anxiety was elaborated. Stigmasterol might be the core bioactive component, while ACHE and MAOA might be the core target genes in the pharmacological profile of bupleurum on anxiety.


Assuntos
Ansiolíticos , Bupleurum , Medicamentos de Ervas Chinesas , Estigmasterol/farmacologia , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Simulação de Acoplamento Molecular , Estigmasterol/química
12.
Sci Rep ; 12(1): 4910, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35318417

RESUMO

Terpenoids from natural plant sources are valuable for their diverse biological activities that have important roles in the medical and agrochemical industries. In this study, we assessed the antioxidant, antifungal, and aphicidal activities of a mixture of spinasterol and 22,23-dihydrospinasterol from the leaves of Citrullus colocynthis. We used 1,1-diphenyl-2-picrylhydrazyl (DPPH) to assess antioxidant activity, and we measured antifungal activity using mycelium growth inhibition assays with three pathogenic fungi, Magnaporthe grisea, Rhizoctonia solani, and Phytophthora infestans. Aphicidal activity against adults of Myzus persicae was determined using in vitro and in vivo assays. Spinasterol and 22,23-dihydrospinasterol exhibited moderate antioxidant activity, even at lower concentrations: 19.98% at 0.78 µg mL-1, 31.52% at 3.0 µg mL-1, 36.61% at 12.5 µg mL-1, and 49.76% at 50 µg mL-1. Spinasterol and 22,23-dihydrospinasterol showed reasonable levels of fungicidal activity toward R. solani and M. grisea, with EC50 values of 129.5 and 206.1 µg mL-1, respectively. The positive controls boscalid and carbendazim were highly effective against all fungi except boscalid for M. grisea (EC50 = 868 µg mL-1) and carbendazim for P. infestans (EC50 = 8721 µg mL-1). Significant insecticidal activity was observed in both residual and greenhouse assays, with LC50 values of 42.46, 54.86, and 180.9 µg mL-1 and 32.71, 42.46, and 173.8 µg mL-1 at 72, 48, and 24 h, respectively. The antioxidant activity of spinasterol and 22,23-dihydrospinasterol was strongly positively correlated with their antifungal and insecticidal activity. Spinasterol and 22,23-dihydrospinasterol therefore show good antioxidant and aphicidal activity with moderate fungicidal activity, making them suitable candidates for an alternative to synthetic agents.


Assuntos
Citrullus colocynthis , Triterpenos , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Folhas de Planta , Sitosteroides , Estigmasterol/análogos & derivados , Triterpenos/farmacologia
13.
PLoS One ; 17(3): e0265420, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35298541

RESUMO

Human papillomavirus (HPV) induced cervical cancer is becoming a major cause of mortality in women. The present research aimed to identify the natural inhibitors of HPV-18 E1 protein (1R9W) from Himalayan herbs with lesser toxicity and higher potency. In this study, one hundred nineteen phytoconstituents of twenty important traditional medicinal plants of Northwest Himalayas were selected for molecular docking with the target protein 1R9W of HPV-18 E1 Molecular docking was performed by AutoDock vina software. ADME/T screening of the bioactive phytoconstituents was done by SwissADME, admetSAR, and Protox II. A couple of best protein-ligand complexes were selected for 100 ns MD simulation. Molecular docking results revealed that among all the selected phytoconstituents only thirty-five phytoconstituents showed the binding affinity similar or more than the standard anti-cancer drugs viz. imiquimod (-6.1 kJ/mol) and podofilox (-6.9 kJ/mol). Among all the selected thirty-five phytoconstituents, eriodictyol-7-glucuronide, stigmasterol, clicoemodin and thalirugidine showed the best interactions with a docking score of -9.1, -8.7, -8.4, and -8.4 kJ/mol. Based on the ADME screening, only two phytoconstituents namely stigmasterol and clicoemodin selected as the best inhibitor of HPV protein. MD simulation study also revealed that stigmasterol and clicoemodin were stable inside the binding pocket of 1R9W, Stigmasterol and clicoemodin can be used as a potential investigational drug to cure HPV infections.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Papillomavirus Humano 18 , Humanos , Simulação de Acoplamento Molecular , Papillomaviridae , Estigmasterol , Neoplasias do Colo do Útero/tratamento farmacológico
14.
Phytochemistry ; 198: 113156, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35248579

RESUMO

Sterols (STs) have a key role in regulating the fluidity and permeability of membranes in plants (phytosterols) that have wide structural diversity. We studied the effect of structural STs diversity on salt tolerance in halophytes. Specifically, we used gas chromatography-mass spectrometry (GC-MS), including two-dimensional gas chromatography-mass spectrometry (GCxGC-MS), to assess the STs composition in leaves of 21 species of wild-growing halophytes from four families (Asteraceae, Chenopodiaceae, Plumbaginaceae, Tamaricaceae) and three ecological groups (Euhalophytes (Eu), recretophytes (Re), salt excluders (Ex)). Fifteen molecular species of STs from three main groups, Δ5-, Δ7-and Δ0- STs (stanols), were detected. Plants of the genus Artemisia were characterized by a high content of stigmasterol (30-49% of the total STs), while ß-sitosterol was the major compound in two Limonium spp., where it comprised 84-92% of the total STs. Species of Chenopodiaceae were able to accumulate both Δ5-and Δ7-STs and stanols. The content of the predominant Δ5-STs decreased in the order Ex → Re → Eu. Molecular species with a saturated steroid nucleus were identified in Eu and Re, suggesting their special salt-accumulating and salt-releasing functions. The structural analogues of stigmasterol, having a double bond C-22, were stigmasta-7,22-dien-3ß-ol (spinasterol) and stigmast-22-en-3ß-ol (Δ7--sitosterol). The ratio of Δ5-stigmasterol/Δ5-ß-sitosterol increased in Ex plants, and spinasterol/Δ7--sitosterol and 22-stigmastenol/sitostanol increased in Eu plants. These data support the well-known role of stigmasterol and its isomers in plant responses to abiotic and biotic factors. The variability in STs types and their ratios suggested some involvement of the sterol membrane components in plant adaptation to growth conditions. The balance of Δ5-, Δ7-and stanols, as well as the accumulation of molecular analogues of stigmasterol, was suggested to be associated with salt tolerance of the plant species in this investigation.


Assuntos
Chenopodiaceae , Fitosteróis , Humanos , Fitosteróis/análise , Tolerância ao Sal , Plantas Tolerantes a Sal , Esteróis , Estigmasterol
15.
J Sci Food Agric ; 102(11): 4759-4769, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35218222

RESUMO

BACKGROUND: Phytosterols are considered to be one of the most promising gelators for obtaining oleogel because of their additional health benefits and natural coexist with vegetable oils. Previous studies have confirmed that individual phytosterols are not capable of structuring vegetable oils unless they act synergistically with other components. However, based on the self-assembly properties of stigmasterol (ST) in organic solvents, we speculate that it can also structure vegetable oils as a gelator alone. RESULTS: For the first time, the present study confirmed the feasibility of using ST alone as a gelator for structuring of vegetable oils, including rapeseed oil (RSO), olive oil (OLO) and flaxseed oil (FSO). RSO had the lowest ST gelation concentration (4%, w/w), and the oil-binding capacity and firmness value of the oleogels were the highest. The rheological results showed that all the samples were gelatinous (G' > G″). The results of differential scanning calorimeter and X-ray diffraction further confirmed that the properties of RSO-based oleogels are superior to those prepared by OLO and FSO. The microscopic results also confirmed that the crystal structure of RSO oleogels was more uniform, smaller and more densely distributed. CONCLUSION: The structural properties of the oleogels were positively correlated with the ST concentration, and various analysis indicators showed that the performance of the oleogel based on RSO was better than that of OLO and FSO. In summary, the present study used ST as a gelator to successfully prepare oleogels with excellent properties, which provides a feasible reference for researchers in related fields. © 2022 Society of Chemical Industry.


Assuntos
Fitosteróis , Estigmasterol , Compostos Orgânicos/química , Óleos Vegetais/química
16.
Biomed Chromatogr ; 36(4): e5309, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34981527

RESUMO

Fucosterol is the main phytosterol in brown algae with various pharmacological effects such as cholesterol-lowering, anticancer, hepatoprotection and neuroprotection. Little is known about the pharmacokinetics and excretion characteristics of fucosterol. In this study, a GC-MS method was developed and validated for the determination of fucosterol in rat plasma, urine and feces. The method effectively avoids the interference of Δ5 -avenasterol, a cis-trans-isomer of fucosterol derived from feed, by using a TG-5 capillary column (a nonpolar column with 5% phenyl-methylpolysilicone as stationary phase material). The linearity ranges were fucosterol 0.300-18.0 µg/ml (R2 = 0.9960) for plasma, 0.0500-2.50 µg/ml for the urine sample (R2 = 0.9963) and 0.100-8.00 µg/mg (R2 = 0.9923) for the feces sample. With good extraction recoveries and stability, this rapid and sensitive method was successfully applied to the pharmacokinetic and excretion studies of fucosterol in Sprague-Dawley rats. Fucosterol from Sargassum fusiforme had poor absorption and slow elimination with an absolute oral bioavailability of 0.74%, and was mainly eliminated through fecal excretion.


Assuntos
Líquidos Corporais , Estigmasterol , Animais , Fezes , Ratos , Ratos Sprague-Dawley , Estigmasterol/análogos & derivados
17.
Chem Biodivers ; 19(3): e202100848, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34997687

RESUMO

Sargassum fusiformis is among the most important edible brown seaweeds in Eastern Asia that contains various bioactive compounds and strong activities. Saringosterol acetate (SA) was successfully isolated from S. fusiformis in our previous research. In this study, SA was investigated for its anticancer effect on MCF-7 breast cancer cells. SA attenuated the survival rate of MCF-7 cells with an IC50 value of 63.16±3.6 µg/mL. Staining with Hoechst 33342 demonstrated that SA treatment mediated apoptotic body generation. SA significantly downregulated Bcl-xL and upregulated Bax, and cleaved PARP, and cleaved caspase 3 in a dose-dependent manner. Thus, these results suggest that SA induced mitochondria-mediated apoptosis in MCF-7 cells, making it a plausible candidate for drug development against breast cancer.


Assuntos
Neoplasias da Mama , Sargassum , Acetatos/farmacologia , Apoptose , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Células MCF-7 , Mitocôndrias , Estigmasterol/análogos & derivados
18.
PLoS One ; 17(1): e0258980, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35085233

RESUMO

In this study, 5 sterols were isolated and purified from Laminaria japonica, commonly known as edible brown seaweed, and their structures were identified based on detailed chemical methods and spectroscopic analyses. Spectroscopic analyses characterized 5 sterols as 29-Hydroperoxy-stigmasta-5,24(28)-dien-3ß-ol, saringosterol (24-vinyl-cholest-5-ene-3ß,24-diol), 24-methylenecholesterol, fucosterol (stigmasta-5,24-diene-3ß-ol), and 24-Hydroperoxy-24-vinyl-cholesterol. The bioactivities of these sterols were tested using lipid peroxidation (LPO) and cyclooxygenase (COX-1 and -2) enzyme inhibitory assays. Fucosterol exhibited the highest COX-1 and -2 enzyme inhibitory activities at 59 and 47%, respectively. Saringosterol, 24-methylenecholesterol and fucosterol showed higher LPO inhibitory activity at >50% than the other compounds. In addition, the results of molecular docking revealed that the 5 sterols were located in different pocket of COX-1 and -2 and fucosterol with tetracyclic skeletons and olefin methine achieved the highest binding energy (-7.85 and -9.02 kcal/mol) through hydrophobic interactions and hydrogen bond. Our results confirm the presence of 5 sterols in L. japonica and its significant anti-inflammatory and antioxidant activity.


Assuntos
Colesterol/análogos & derivados , Inibidores de Ciclo-Oxigenase/farmacologia , Laminaria/química , Peroxidação de Lipídeos/efeitos dos fármacos , Esteróis/farmacologia , Colesterol/química , Colesterol/farmacologia , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Conformação Proteica , Esteróis/química , Estigmasterol/análogos & derivados , Estigmasterol/química , Estigmasterol/farmacologia
19.
Chirality ; 34(2): 396-420, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34788903

RESUMO

Diastereoisomeric stigmasterol oxiranes 4, 5, 8, and 9 are known phytosterol oxidation products (POPs) that have been evaluated for their cytotoxicity, although the results are of limited significance since, in most cases, they were evaluated as mixtures. Consequently, to establish biological activity hierarchy of these oxides, it is critical to evaluate individual pure POPs. Therefore, we now describe the obtention of individual molecules and their absolute configuration (AC) determination. The two acetylated C-5-C-6 oxiranes 6 and 7; the two acetylated C-22-C-23 oxides 10 and 11, obtained by means of Δ5 double bond protection-deprotection; and the four C-5-C-6, C-22-C-23 diepoxystigmasteryl acetates 19-22 were now individually gained and their AC determined by vibrational circular dichroism. Vibrational modes associated with the C-5-C-6 and the C-22-C-23 bonds were identified in dioxiranes 19-22 and used to assign the AC of monoepoxides 6, 7, 10, and 11. The AC of biological active non-acetylated molecules follows immediately. Due to the scarce spectroscopic information available for these POPs, the 1 H and 13 C NMR chemical shifts of 3-22 were assigned using 1D- and 2D-NMR experiments.


Assuntos
Compostos de Epóxi , Estigmasterol , Dicroísmo Circular , Estrutura Molecular , Estereoisomerismo , Vibração
20.
Anticancer Agents Med Chem ; 22(7): 1363-1369, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33906591

RESUMO

BACKGROUND: Survival and progression of cancer cells are highly dependent on aerobic glycolysis. Strobilanthes crispus has been shown to have promising anticancer effects on breast cancer cells. The involvement of the glycolysis pathway in producing these effects is unconfirmed, thus further investigation is required to elucidate this phenomenon. OBJECTIVE: This study aims to determine the effect of S. crispus active fraction (F3) and its bioactive components on glycolysis in triple-negative breast cancer cells (MDA-MB-231). METHODS: This study utilizes F3, lutein, ß-sitosterol, and stigmasterol to be administered in MDA-MB-231 cells for measurement of antiglycolytic activities through cell poliferation, glucose uptake, and lactate concentration assays. Cell proliferation was assessed by MTT assay of MDA-MB-231 cells after treatment with F3 and its bioactive components lutein, ß-sitosterol, and stigmasterol. The IC50 value in each compound was determined by MTT assay to be used in subsequent assays. The determination of glucose uptake activity and lactate concentration were quantified using fluorescence spectrophotometry. RESULTS: Antiproliferative activities were observed for F3 and its bioactive components, with IC50 values of 100 µg/mL (F3), 20 µM (lutein), 25 µM (ß-sitosterol), and 90 µM (stigmasterol) in MDA-MB-231 cells at 48 h. The percentage of glucose uptake and lactate concentration in MDA-MB-231 cells treated with F3, lutein, or ß sitosterol were significantly lower than those observed in the untreated cells in a time-dependent manner. However, treatment with stigmasterol decreased the concentration of lactate without affecting the glucose uptake in MDA-MB-231 cells. CONCLUSION: The antiglycolytic activities of F3 on MDA-MB-231 cells are attributed to its bioactive components.


Assuntos
Acanthaceae , Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Glucose , Humanos , Lactatos/farmacologia , Luteína/farmacologia , Extratos Vegetais/farmacologia , Estigmasterol/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo
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