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1.
Artigo em Inglês | MEDLINE | ID: mdl-31841978

RESUMO

Steroids are essential hormones that play a crucial role in homeostasis of many biological processes including sexual development, spermatogenesis, sperm physiology and fertility. Although steroids have been largely studied in many biological matrices (such as urine and plasma), there is very limited information of the steroid content and their study as potential indicators of the quality of the seminal fluid. In this study, a LC-HRMS (liquid chromatography-high resolution mass spectrometry) strategy has been developed in order to obtain the extended steroid profile of human seminal fluid. A comparison between supported liquid extraction (SLE) and solid liquid extraction (SPE) was carried out and the chosen SPE method was further optimized to evidence the largest possible number of compounds. Steroids were automatically annotated by using DynaStI, a publicly available retention time prediction tool developed in our lab, to match the experimental data (i.e. accurate mass and tR). Altogether, these resources allowed us to develop a post-targeted approach able to consistently detect 41 steroids in seminal fluid (with half of them being androgens). Such steroid pattern was found to be stable across different extraction times and injection days. In addition to accurate mass and retention time, the identity of 70% of the steroids contained in such steroid profile was confirmed by comparing their fragmentation patterns in real samples to those of pure commercial standards. Finally, the workflow was applied to compare and distinguish the steroid profile in seminal fluid from healthy volunteers (n = 7, with one of them being a vasectomized subject). In all, the developed steroidomics strategy allows to reliably monitor an extended panel of 41 steroids in human seminal fluid.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Sêmen/química , Esteroides/análise , Humanos , Masculino , Metaboloma , Metabolômica , Sêmen/metabolismo , Extração em Fase Sólida , Esteroides/isolamento & purificação
2.
Phytochemistry ; 168: 112109, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494344

RESUMO

Eight undescribed ergostane-type steroids, (22E,24R)-ergosta-7,22-dien-3ß,5α-diol- 6,5-olide, (22E,24R)-ergosta-7,9(11),22-trien-3ß,5ß,6ß-triol, (22E,24R)-6ß-methoxy ergosta-7,9(11),22-trien-3ß,5α,14ß-triol, (22E,24R)-9α,15α-dihydroxyergosta-4,6,8 (14),22-tetraen-3-one, (22E,24R)-ergosta-5,8,22-trien-3ß,11α-dihydroxyl-7-one, (22E,24R)-ergosta-4,7,22-trien-3ß,9α,14ß-trihydroxyl-6-one, (22E,24R)-ergosta-7,22- dien-3ß,9α,14ß-trihydroxyl-6-one, and (22E,24R)-6ß-methoxyergosta-7,22-dien-3ß, 5α,9α,14ß-tetraol, and twenty-one known analogues were isolated from the fruiting bodies of Ganoderma resinaceum Boud. Their chemical structures were determined on the basis of comprehensive spectroscopic analysis and X-ray crystal diffraction, as well as empirical pyridine-induced deshielding effects. Furthermore, selected compounds were evaluated for their inhibitory effects on macrophage activation using an inhibition of nitric oxide production assay. Finally, (22E,24R)-ergosta-5,8,22- trien-3ß,11α-dihydroxyl-7-one, (22E,24R)-ergosta-4,7,22-trien-3ß,9α,14ß-tri hydroxyl-6-one, (22E,24R)-6ß-methoxyergosta-7,22-dien-3ß,5α,9α,14ß-tetraol, (22E,24R)-ergosta-6,9,22-trien-3ß,5α,8α-triol,ergost-6,22-dien-3ß,5α,8α-triol, 5α,6α-epoxy-(22E,24R)-ergosta-8,22-diene-3ß,7α-diol, 5α,6α-epoxy-(22E,24R)- ergosta-8(14),22-diene-3ß,7α-diol, 5α,6α-epoxy-(22E,24R)-ergosta-8(14),22-diene-3ß, 7ß-diol, and 22E-7α-methoxy-5α,6α-epoxyergosta-8(14),22-dien-3ß-ol showed inhibitory effects on NO production with IC50 values ranging from 3.24 ±â€¯0.02 to 35.19 ±â€¯0.41 µM compared with L-NMMA (IC50 49.86 ±â€¯2.13 µM), indicating that they have potential anti-inflammatory activity.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Carpóforos/química , Ganoderma/química , Esteroides/isolamento & purificação , Esteroides/farmacologia , Animais , Anti-Inflamatórios/química , Relação Dose-Resposta a Droga , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Conformação Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Esteroides/química
3.
Mar Drugs ; 17(9)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514359

RESUMO

Two new steroids, dendronesterones D (1) and E (2), featuring with 1,4-dienone moiety, along with three known steroids, methyl 3-oxochola-4,22-diene-24-oate (3), 5α,8α-epidioxy-24(S)- methylcholesta-6,22-dien-3ß-ol (4), and 5α,8α-epidioxy-24(S)-methylcholesta-6,9(11),22-trien-3ß-ol (5), were isolated from an octocoral Dendronephthya sp. The structures of steroids 1 and 2 were elucidated by using spectroscopic methods and steroid 1 was found to exhibit significant in vitro anti-inflammatory activity in lipopolysaccharides (LPS)-induced RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein.


Assuntos
Antozoários/química , Anti-Inflamatórios/farmacologia , Esteroides/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Células RAW 264.7 , Esteroides/isolamento & purificação
4.
Fitoterapia ; 137: 104281, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381957

RESUMO

Veratrum californicum is a rich source of steroidal alkaloids, many of which have proven to be antagonists of the Hedgehog (Hh) signaling pathway that becomes aberrant in over twenty types of cancer. These alkaloids first became known in the 1950's due to their teratogenic properties, which resulted in newborn and fetal lambs developing cyclopia as a result of pregnant ewes consuming Veratrum californicum. It was discovered that the alkaloids in V. californicum were concentrated in the root and rhizome of the plant with much lower amounts of the most active alkaloid, cyclopamine, present in the aerial plant, especially in the late growth season. Inspired by the limitations in analytical instrumentation and methods available to researchers at the time of the original investigation, we have used state-of-the-art instrumentation and modern analytical methods to quantitate four steroidal alkaloids based on study parameters including plant part, harvest location, and growth stage. The results of the current inquiry detail differences in alkaloid composition based on the study parameters, provide a detailed assessment for alkaloids that have been characterized previously (cyclopamine, veratramine, muldamine and isorubijervine), and identify at least six alkaloids that have not been previously characterized. This study provides insight into optimal harvest time, plant growth stage, harvest location, and plant part required to isolate, yet to be characterized, alkaloids of interest for exploration as Hh pathway antagonists with desirable medicinal properties.


Assuntos
Alcaloides/química , Esteroides/química , Veratrum/química , Alcaloides/isolamento & purificação , Proteínas Hedgehog/antagonistas & inibidores , Idaho , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Componentes Aéreos da Planta/química , Rizoma/química , Estações do Ano , Esteroides/isolamento & purificação , Alcaloides de Veratrum
5.
Fitoterapia ; 137: 104268, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306720

RESUMO

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


Assuntos
Alcaloides/farmacologia , Glicosídeos/farmacologia , Solanum nigrum/química , Esteroides/farmacologia , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , China , Frutas/química , Glicosídeos/isolamento & purificação , Humanos , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Células RAW 264.7 , Esteroides/isolamento & purificação
6.
Org Biomol Chem ; 17(24): 5925-5928, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31165123

RESUMO

A novel ergostane, sarocladione (1), was isolated from the deep-sea-derived fungus Sarocladium kiliense, along with 20 known compounds. The structure of 1 was determined mainly by a detailed analysis of its experimental and calculated NMR spectroscopic data. It is worth noting that 1 was the first steroid bearing a 5,10:8,9-diseco moiety. All 21 compounds were tested for in vitro antitumor activities against five cancer cell lines. ß-Sitostenone (7) and 4,6-dihydroxyeudesmane (20) showed significant effects on HeLa-S3 cells with the IC50 values of 9.2 µM and 9.3 µM, respectively.


Assuntos
Acremonium/química , Antineoplásicos/farmacologia , Esteroides/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Conformação Molecular , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-Atividade
7.
Phytochemistry ; 164: 172-183, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158602

RESUMO

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


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Glicosídeos/farmacologia , Polygonatum/química , Rizoma/química , Esteroides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-Atividade
8.
Pak J Pharm Sci ; 32(2): 721-741, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31081788

RESUMO

Present review discuss the reported work on structures, origins and the potent biologically active natural products isolated from Genus Buddleja, which is known for having many important pharmacologically active substances. The Genus Buddleja have more than 100 species, many of them are distributed in Mediterranean and Asian regions. A very small number of common species of the Genus in majority of fruiting plants have been investigated for their biological potential. So for, isolation of about 153 or more new/novel chemical substances have been reported. Purposes of the review is to discuss the structurally established and pharmacologically significant natural substances from wide variety of different species of this genus. Traditionally, species of the genus are reported to be used for healing, treatment of liver diseases, bronchial complaints, preventing several other diseases by exhibiting diuretic properties, sedative functions, analgesic potential, antirheumatic actions, antimicrobial activities, anti hyperglycemic functions and antioxidant properties. In this review we will describe recently established medicinal chemistry aspects and complete list of phytoconstituents as well as their sources and reference.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Buddleja/química , Parassimpatolíticos/farmacologia , Plantas Medicinais/química , Analgésicos/farmacologia , Animais , Anti-Infecciosos/química , Antioxidantes/química , Buddleja/metabolismo , Diuréticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Humanos , Hipnóticos e Sedativos/farmacologia , Parassimpatolíticos/química , Plantas Medicinais/metabolismo , Esteroides/química , Esteroides/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificação
9.
Int J Mol Sci ; 20(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035460

RESUMO

A total of 85 strains of lactic acid bacteria were isolated from corn silage in this study and analyzed in vitro for their cholesterol removal, NPC1L1 protein down-regulation and bile salt deconjugation ability, respectively. Nineteen strains were selected for further analysis for their probiotic potential. Finally, 3 strains showing better probiotic potential were evaluated for their cholesterol-lowering activity in hamsters. The strains showing the greater cholesterol removal and NPC1L1 protein down-regulation activity had no significant effects on serum and hepatic cholesterol levels in hamsters (p > 0.05). However, Lactobacillus plantarum CAAS 18008 (1 × 109 CFU/d) showing the greater bile salt deconjugation ability significantly reduced serum low-density lipoprotein cholesterol, total cholesterol, and hepatic total cholesterol levels by 28.8%, 21.7%, and 30.9%, respectively (p < 0.05). The cholesterol-lowering mechanism was attributed to its bile salt hydrolase activity, which enhanced daily fecal bile acid excretion levels and thereby accelerated new bile acid synthesis from cholesterol in liver. This study demonstrated that the strains showing greater cholesterol removal and NPC1L1 protein down-regulation activity in vitro hardly reveal cholesterol-lowering activity in vivo, whereas the strains showing greater bile salt deconjugation ability in vitro has large potential to decrease serum cholesterol levels in vivo.


Assuntos
Lactobacillales/isolamento & purificação , Probióticos/isolamento & purificação , Silagem/microbiologia , Zea mays/microbiologia , Animais , Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase , Cricetinae , Fezes/química , Humanos , Lactobacillales/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Proteínas de Membrana/metabolismo , Redes e Vias Metabólicas , Viabilidade Microbiana , Probióticos/metabolismo , Esteroides/química , Esteroides/isolamento & purificação
10.
J Nat Med ; 73(4): 814-819, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31054009

RESUMO

Two new steroidal saponins, scrobiculosides A and B, were isolated from the deep-sea sponge Pachastrella scrobiculosa, collected at a depth of 200 m off Miura Peninsula, Japan. The aglycones of scrobiculosides A and B feature a vinylic cyclopropane and a ∆24,25 exomethylene on the side chains, respectively. Both saponins have a common sugar moiety composed of ß-D-galactopyranosyl-(1 → 2)-6-acetyl-ß-D-glucopyranoside, with the exception of an acetyl group on C6″ in scrobiculoside A. Scrobiculoside A exhibited cytotoxicity against HL-60 and P388 cells, with IC50 values of 52 and 61 µM, respectively.


Assuntos
Poríferos/metabolismo , Saponinas/isolamento & purificação , Saponinas/farmacologia , Esteroides/farmacologia , Animais , Linhagem Celular Tumoral , Células HL-60 , Humanos , Japão , Estrutura Molecular , Saponinas/química , Esteroides/química , Esteroides/isolamento & purificação
11.
Fitoterapia ; 136: 104171, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31085309

RESUMO

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


Assuntos
Cynanchum/química , Células Estreladas do Fígado/efeitos dos fármacos , Raízes de Plantas/química , Esteroides/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Esteroides/isolamento & purificação , Fator de Crescimento Transformador beta1
12.
Chem Biodivers ; 16(6): e1800692, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30957385

RESUMO

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


Assuntos
Antozoários/química , Produtos Biológicos/química , Animais , Antozoários/metabolismo , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia
13.
J Sep Sci ; 42(15): 2471-2481, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31012280

RESUMO

Overcoming epidermal growth factor receptor resistance is a critical problem that needs to be solved in clinical practice. Drugs that downregulate the fatty acid synthase-epidermal growth factor receptor will become novel treatments for non-small cell lung cancer. Solanum nigrum, extracted with water at 4°C, shows strong cytotoxic activity and inhibits tumor growth in Lewis tumor bearing-mice in a dose-dependent manner. A novel active compound in S. nigrum, solaoiacid, was successfully separated and purified from S. nigrum by preparative high-performance liquid chromatography with mass spectrometry and ultra high performance liquid chromatography with time-of-flight tandem mass spectrometry. The IC50 of solaoiacid on lung cancer cells was 2.3 µmol/L, which was significantly lower than that of the known steroidal glycoalkaloid. Label-free proteomics and STRING Network analysis were used to identify significantly deregulated proteins in lung cancer cells that were treated with the fresh ripe fruit extracts of S. nigrum. S. nigrum regulates multiple signal pathways, including the epidermal growth factor receptor pathway. S. nigrum downregulated 24 main proteins with direct roles in fatty acid biosynthesis. Both S. nigrum and solaoiacid showed strong downregulation of the fatty acid synthase-epidermal growth factor receptor and anti-non-small cell lung cancer effects, and thus will become a novel drug for the treatment of non-small cell lung cancer.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Solanum nigrum/química , Esteroides/farmacologia , Células A549 , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Frutas/química , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Esteroides/química , Esteroides/isolamento & purificação
14.
Prep Biochem Biotechnol ; 49(3): 298-306, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30821599

RESUMO

Hyaluronidase (hyase) is a hyaluronic acid (HA) depolymerizing enzyme produced by many pathogenic bacteria as a virulence factor to establish and spread infections. Present studies established that a steroidal fraction (SF) isolated from leaves of Carissa carandas act as a strong hyase inhibitor. The kinetic parameters involved in the inhibition of hyase by purified SF were studied and compared with standard hyase inhibitor quercetin. The purified SF showed the highest inhibition with an IC50 of 5.19 mM in comparison with a standard inhibitor, quercetin (IC50 8.63 mM). The inhibition constant (Ki) of purified SF determined by Dixon plot was 8.32 mM, which was significantly lower than that of quercetin standard. The kinetic behavior of enzyme hyase revealed to be more complex than classical competitive and uncompetitive inhibition where inhibitor affects both Km and Vmax. The inhibitor (I) favored the binding to the enzyme-substrate (ES) complex where Km value appeared to decrease (Kmapp < Km). The inhibitor also leads to decrease in the apparent maximum velocity of the enzyme-substrate reaction (Vmaxapp < Vmax). These results signpost toward mixed nature of inhibition of enzyme hyase by purified SF. Anti-hyaluronidase activity by a bioactive metabolite from C. carandas has not been reported so far and has high therapeutic potential against spread of pathogen and its toxins in the host.


Assuntos
Apocynaceae/química , Inibidores Enzimáticos/farmacologia , Hialuronoglucosaminidase/antagonistas & inibidores , Esteroides/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Hialuronoglucosaminidase/química , Cinética , Folhas de Planta/química , Esteroides/química , Esteroides/isolamento & purificação
15.
Pharm Biol ; 57(1): 176-183, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30860934

RESUMO

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


Assuntos
Cardiotônicos/farmacologia , Insuficiência Cardíaca/prevenção & controle , Ophiopogon/química , Saponinas/farmacologia , Animais , Cardiotônicos/isolamento & purificação , Doença Crônica , Doxorrubicina/toxicidade , Ecocardiografia , Insuficiência Cardíaca/induzido quimicamente , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Masculino , Medicina Tradicional Chinesa/métodos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Saponinas/isolamento & purificação , Esteroides/isolamento & purificação , Esteroides/farmacologia
16.
J Ethnopharmacol ; 235: 309-319, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30772481

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima (Roxb.) Wight et Arn is a vine distributed in southwest area of China and used in folk medicine for treatment of tumors. Recent decades of studies on this plant reveal its synergistic effects with certain anticancer drugs in cancer therapy. In our previous study, an extract ETA which contains total aglycones made from M. tenacissima significantly enhanced antitumor activity of paclitaxel in tumor-bearing mice. However, the effective constituents in ETA and the underlying mechanisms remain unclear. AIM OF THE STUDY: Reveal the active components in ETA as well as the molecular mechanism in enhancing antitumor efficacy of paclitaxel. MATERIAL AND METHODS: Main constituents in ETA were purified by chemical methods. Effects of the purified constituents on metabolic activity of CYP450 enzymes were evaluated in human liver microsomes. Ability of the constituents to enhance antitumor activity of paclitaxel were investigated in nude mice bearing HeLa tumors. Pharmacokinetic study was performed in SD rats. Molecular docking was carried out for investigation of drug-protein interactions. RESULTS: Three main C21 steroidal aglycones, 11α-O-tigloyl-12ß-O-acetyl-tenacigenin B (MT1), 11α-O-2-methylbutanoyl-12ß-O-tigloyl-tenacigenin B (MT2) and 11α-O-2-methylbutanoyl-12ß-O-acetyl-tenacigenin B (MT3), together with tenacigenin B (MT4) was prepared from ETA. Among them, MT1, MT2 and MT3 strongly inhibit the metabolic activity of CYP3A4. MT2 also showed inhibitory effects on CYP2C8, CYP2B6 and CYP2C19. In HeLa tumor xenografts, MT1, MT2 and MT3 (30 mg/kg) did not affect tumor growth themselves, but significantly enhanced paclitaxel-induced growth inhibition. In addition, coadministration of MT2 with paclitaxel resulted in significant reduction of liver CYP2C8. In pharmacokinetic study, MT2 significantly increased the blood concentration of paclitaxel with increased AUC value by 2.2-5.3 folds. Molecular docking analysis suggested hydrophobic interaction modes of tenacigenin B derivatives with CYP3A4, and also the essential roles of the C-11 and C-12 ester groups for effective interaction with CYP3A4. CONCLUSION: Our study proves that, 11α-O-tigloyl-12ß-O-acetyl-tenacigenin B, 11α-O-2-methylbutanoyl-12ß-O-tigloyl-tenacigenin B and 11α-O-2-methylbutanoyl-12ß-O-acetyl-tenacigenin B, which are the main constituents of ETA, are active inhibitors of CYP3A4 with potential to increase therapeutic efficacy of anticancer drugs that are substrates of CYP3A4. Tenacigenin B derivatives with C-11 and C-12 ester group substitutions, or at least a large part of them, are active components in ETA and M. tenacissima to enhance in vivo antitumor efficacies of paclitaxel.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Marsdenia/química , Paclitaxel/farmacologia , Esteroides/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Citocromo P-450 CYP3A/efeitos dos fármacos , Citocromo P-450 CYP3A/metabolismo , Sinergismo Farmacológico , Ésteres/química , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Simulação de Acoplamento Molecular , Paclitaxel/administração & dosagem , Ratos , Ratos Sprague-Dawley , Esteroides/química , Esteroides/isolamento & purificação , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Anal Chim Acta ; 1054: 59-73, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30712594

RESUMO

A new, relatively simple sample processing and detection workflow has been developed for the quantification and confirmation of banned growth-promoting substances in a wide variety of animal-based food products. The method covers all required compounds (belonging to the so-called A1, A3, A4 and B2f groups as termed by the relevant EU legislation) which are currently monitored by the official European community surveillance programs. The sample processing includes a thermal sample denaturation step, intended to prevent undesirable side-reactions during the following enzymatic deconjugation of covalently bound analytes. A pH-adjusted dual liquid/liquid-extraction produces sufficient clean extracts for a wide range of matrices (urine, muscle, liver, serum, full blood). The method has been validated using two hybrid quadrupole high-resolution mass spectrometers (Orbitrap and time-of-flight technology-based instruments). Full-scan data acquisition, interlaced with targeted modes (unit mass isolation of the precursors, followed by collision-induced fragmentation), produces sufficiently sensitive and selective detection of the analytes within all the validated matrices. The proposed method is an alternative to currently used methods that are restricted to a limited set of analytes and matrices.


Assuntos
Análise de Alimentos/métodos , Lactonas/análise , Espectrometria de Massas/métodos , Esteroides/análise , Estilbenos/análise , Métodos Analíticos de Preparação de Amostras , Animais , Concentração de Íons de Hidrogênio , Lactonas/química , Lactonas/isolamento & purificação , Extração Líquido-Líquido , Esteroides/química , Esteroides/isolamento & purificação , Estilbenos/química , Estilbenos/isolamento & purificação
18.
Nat Prod Res ; 33(3): 309-315, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29533080

RESUMO

Chemical investigation of the resinous exudates of Commiphora myrrha has led to the isolation of four sesquiterpenes (1a/1b, 2, and 3), including one pair of new sesquiterpene enantiomers (1a/1b), one new racemic mixture 2, and two steroids (4 and 5). Their structures were elucidated by spectroscopic analysis, and the absolute configurations of 1a/1b were determined by CD analysis. The antimigratory potential of compounds 1-5 were evaluated and compound 3 was found to inhibit human hepatocellular liver carcinoma HepG2 cell migration in dose-dependent manner.


Assuntos
Commiphora/química , Resinas Vegetais/química , Sesquiterpenos/isolamento & purificação , Esteroides/isolamento & purificação , Carcinoma Hepatocelular/patologia , Movimento Celular , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Estrutura Molecular , Sesquiterpenos/química , Esteroides/química
19.
Nat Prod Res ; 33(9): 1340-1344, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29863897

RESUMO

A new steroid, (3S,5R,9R,10S,13R,17R,20R,24S,22E)-ergosta-6,8,22-triene-3,25-diol (1), and its sulfonated analogue (2) together with a known one, 5α,8α-epidioxy-cholest-6-en-3ß-ol (3) were isolated from the marine sponge Dactylospongia elegans collected from the South China Sea. The new structures including absolute configurations were established by the HRESIMS and 1D and 2D NMR analysis coupled with the X-ray crystal analysis. Both of 1 and 2 exhibited cytotoxicity against cancer cell line MCF-7 with IC50 values of 9.7 and 8.5 µM, respectively.


Assuntos
Antineoplásicos/farmacologia , Poríferos/química , Esteroides/química , Esteroides/farmacologia , Animais , Antineoplásicos/química , Organismos Aquáticos/química , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Esteroides/isolamento & purificação
20.
Nat Prod Res ; 33(13): 1885-1890, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29865893

RESUMO

A new pregnane steroid, named aspergillon A (1), together with two known compounds, (22E,24R)-ergosta-5,7,22-trien-3ß-ol (2) and (22E, 24R)-ergosta-4,6,8(14),22-tetraen-3-one (3) were isolated from cultures of the tin mine tailings-associated fungus Aspergillus versicolor. The new structure and absolute configuration were determined with the help of extensive spectroscopic analyses and quantum chemical calculations of the electronic circular dichroism (ECD) spectra.


Assuntos
Aspergillus/química , Pregnanos/isolamento & purificação , Esteroides/isolamento & purificação , Dicroísmo Circular , Fungos , Mineração , Estrutura Molecular , Pregnanos/química , Análise Espectral , Esteroides/química
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