Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.255
Filtrar
1.
J Nat Med ; 74(4): 741-749, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32601830

RESUMO

Cancer cachexia is a complex and multifactorial syndrome that influences about 50-80% of cancer patients and may lead to 20% of cancer deaths and muscle atrophy is the key characteristic of the syndrome. Recent researches have shown that myostatin is a negative regulator in the growth and differentiation of skeletal muscle. Herein, C2C12 cancer cachexia model was established with C26 conditioned culture medium (CCM), then treated with magnolol to evaluate the pharmacological activity of magnolol in myotube atrophy. Our results demonstrated that magnolol inhibited the activity of myostatin promotor and the myostatin signaling pathway. In C2C12 cancer cachexia model, magnolol decreased myostatin expression, inhibited the phosphorylation of SMAD2/3 activated by C26 conditioned culture medium (CCM), and elevated the phosphorylation of FOXO3a lowered by CCM. Myosin heavy chain (MyHC), myogenin (MyoG), and myogenic differentiation (MyoD), as three common myotube markers in C2C12 myotube, were decreased by CCM, which could be effectively reversed by magnolol via activation of AKT/mTOR-regulated protein synthesis and inhibition of ubiquitin-mediated proteolysis. This study reveals that magnolol inhibits myotube atrophy induced by CCM by increasing protein synthesis and decreasing ubiquitin-mediated proteolysis, so that magnolol is a promising leading compound in treating muscle atrophy induced by cancer cachexia.


Assuntos
Anti-Inflamatórios não Esteroides/química , Produtos Biológicos/química , Compostos de Bifenilo/química , Caquexia/tratamento farmacológico , Lignanas/química , Fibras Musculares Esqueléticas/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Miostatina/metabolismo , Neoplasias/complicações , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Transfecção
2.
J Nat Med ; 74(4): 750-757, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32621255

RESUMO

Artemisia sieversiana is an annual herbaceous plant distributed throughout Central and East Eurasia and is regarded as an undesirable forage plant in Mongolia. It affects livestock, so information about its chemical composition is needed. We isolated three new sesquiterpenoids (1-3) and known compounds from A. sieversiana and investigated their activities. The absolute configuration of 1 was established using single-crystal X-ray diffraction crystallography, and its configuration differed from those of reported compounds with similar structures. Two additional new sesquiterpenoids (2 and 3) with similar structures were identified, and their configurations were determined. The trypanocidal activities of the isolated compounds (1-18) against Trypanosoma congolense and the pathogen responsible for fatal trypanosomosis in animals were estimated. Flavonoids and lignans were identified as active compounds with IC50 values ranging from 2.9 to 90.2 µM.


Assuntos
Artemisia/química , Flavonoides/química , Lignanas/química , Plantas/química , Sesquiterpenos/química , Estrutura Molecular , Mongólia
3.
Microb Cell Fact ; 19(1): 82, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245478

RESUMO

BACKGROUND: Dietary lignans belong to the group of phytoestrogens together with coumestans, stilbenes and isoflavones, and themselves do not exhibit oestrogen-like properties. Nonetheless, the gut microbiota converts them into enterolignans, which show chemical similarity to the human oestrogen molecule. One of the richest dietary sources of lignans are oilseeds, including flaxseed. The aim of this pilot study was to determine the concentration of the main dietary lignans in an oilseed mix, and explore the gut microbiota-dependent production of enterolignans for oestrogen substitution in young and premenopausal women. The oilseed mix was fermented in a pH-controlled batch culture system inoculated with women's faecal samples. The lignan content and enterolignan production were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and the faecal-derived microbial communities were profiled by 16S rRNA gene-based next-generation sequencing. RESULTS: In vitro batch culture fermentation of faecal samples inoculated with oilseed mix for 24 h resulted in a substantial increase in enterolactone production in younger women and an increase in enterodiol in the premenopausal group. As for the gut microbiota, different baseline profiles were observed as well as different temporal dynamics, mainly related to Clostridiaceae, and Klebsiella and Collinsella spp. CONCLUSIONS: Despite the small sample size, our pilot study revealed that lignan-rich oilseeds could strongly influence the faecal microbiota of both younger and premenopausal females, leading to a different enterolignan profile being produced. Further studies in larger cohorts are needed to evaluate the long-term effects of lignan-rich diets on the gut microbiota and find out how enterolactone-producing bacterial species could be increased. Diets rich in lignans could potentially serve as a safe supplement of oestrogen analogues to meet the cellular needs of endogenous oestrogen and deliver numerous health benefits, provided that the premenopausal woman microbiota is capable of converting dietary precursors into enterolignans.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Lignanas/química , Óleos Vegetais/química , Estudos de Casos e Controles , Feminino , Humanos , Projetos Piloto , Pré-Menopausa
4.
Z Naturforsch C J Biosci ; 75(3-4): 103-112, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32187019

RESUMO

The current study aimed to evaluate the in vivo hypoglycemic potential of Myristica fragrans seed extract co-administered with glimepiride in Swiss albino mice. Computational tools were used to further verify the in vivo findings and to help compare this combination to the glimepiride-pioglitazone combination in terms of the binding affinity of the ligands to their respective target protein receptors and the relative stability of the drug-protein complexes. The effect of the combined therapy was observed both in alloxan- and glucose-induced hyperglycemic Swiss albino mice. The mean fasting blood glucose level of the test groups was measured and statistically evaluated using Student's t test. The combined therapy significantly reduced the blood glucose level in a time-dependent manner compared to glimepiride alone. The binding affinity of glimepiride was found to be -7.6 kcal/mol with sulfonylurea receptor 1 in molecular docking. Conversely, macelignan-peroxisome proliferator-activated receptor (PPAR) α and macelignan-PPAR γ complexes were stabilized with -9.2 and -8.3 kcal/mol, respectively. Molecular dynamic simulation revealed that macelignan-PPAR α and γ complexes were more stable than pioglitazone complexes. The combination shows promise in animal and computer models and requires further trials to provide evidence of its activity in humans.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Lignanas/administração & dosagem , Myristica/química , Compostos de Sulfonilureia/administração & dosagem , Aloxano/efeitos adversos , Animais , Diabetes Mellitus Tipo 2/induzido quimicamente , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Glucose/efeitos adversos , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Lignanas/química , Lignanas/farmacologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , PPAR alfa/metabolismo , PPAR gama/metabolismo , Pioglitazona/administração & dosagem , Pioglitazona/farmacologia , Extratos Vegetais/química , Compostos de Sulfonilureia/química , Compostos de Sulfonilureia/farmacologia , Fatores de Tempo
5.
J Chromatogr A ; 1618: 460942, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32057448

RESUMO

The fruit of Schisandra chinensis (Chinese magnolia vine), the medicinal plant well-known in Traditional Chinese Medicine, gains great popularity in the modern phytopharmacology. This phenomena is related to the wide and powerful healing properties, including supporting immune, nervous and digestive systems activity. S. chinensis is also known for its adaptogenic properties which can support the treatment of neurodegenerative disorders, particularly Alzheimer's disease. The components of S. chinensis have been analyzed mostly using chromatography, including HPLC, GC and TLC. The last technique can be easily hyphenated with biological assays performed directly on a TLC plate that is using effect directed detection. TLC-direct bioautography (TLC-DB) for acetylcholinesterase (AChE) inhibition and TLC-DB against Bacillus subtilis were performed, followed by micro-preparative separation of fractions which were subsequently subjected to LC-MS tentative identification. Additionally, screening analysis was done using both biological detection and derivatization reagents (e.g. PMA, thymol, NP-PEG). Both TLC screening and effect-directed analysis (TLC-DB followed by MS analysis) of S. chinensis fruit revealed components with biological activity, especially antibacterials (e.g. citric acid) and inhibitors of AChE (mainly dibenzocyclooctadiene lignans). AChE inhibition activities were confirmed by TLC-DB for nine standards that is: 6-O-benzoylgomisin, deoxyschisandrin, gomisin A, gomisin G, schisandrin, schisandrin C, schisanhenol, schisantherin A and schisantherin B. These lignans were further identified by LC-ESI-MS in the isolated fraction revealing AChE inhibition. Moreover three other lignans: γ-schisandrin, schisandrin B and gomisin J were tentatively identified by LC-ESI-MS.


Assuntos
Cromatografia em Camada Delgada/métodos , Lignanas/análise , Schisandra/química , Acetilcolinesterase , Inibidores da Colinesterase/análise , Inibidores da Colinesterase/química , Cromatografia Líquida , Ciclo-Octanos/análise , Frutas/química , Lignanas/química , Espectrometria de Massas
6.
AAPS PharmSciTech ; 21(2): 62, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925586

RESUMO

The study mainly aimed to improve the solubility of honokiol (HK) by preparing honokiol nanosuspensions (HNS). In this study, HNS were obtained using Kolliphor®P407 (P407) as a stabilizer through melting method combined with high pressure homogenization (HPH). The crystalline state of HNS was confirmed through differential scanning calorimetry (DSC) and X-ray Diffraction (XRD). In vitro, the dissolution rate of HNS was significantly improved than that of pure HK. In vivo, higher anti-inflammatory activity was achieved after free HK had been made into HNS. There was no significant difference between the degree of edema (DE) of HNS group and that of aspirin group. Consequently, melting method combined with HPH was a potent technique to prepare HNS. Furthermore, nanosuspension was a valid formulation that could be utilized to enhance the anti-inflammatory effect of HK.


Assuntos
Anti-Inflamatórios/farmacologia , Compostos de Bifenilo/farmacologia , Lignanas/farmacologia , Animais , Compostos de Bifenilo/química , Feminino , Lignanas/química , Masculino , Camundongos , Nanopartículas/química , Solubilidade , Suspensões
7.
Molecules ; 25(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906391

RESUMO

Lignans are widely produced by various plant species; they are a class of natural products that share structural similarity. They usually contain a core scaffold that is formed by two or more phenylpropanoid units. Lignans possess diverse pharmacological properties, including their antiviral activities that have been reported in recent years. This review discusses the distribution of lignans in nature according to their structural classification, and it provides a comprehensive summary of their antiviral activities. Among them, two types of antiviral lignans-podophyllotoxin and bicyclol, which are used to treat venereal warts and chronic hepatitis B (CHB) in clinical, serve as examples of using lignans for antivirals-are discussed in some detail. Prospects of lignans in antiviral drug discovery are also discussed.


Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Lignanas/química , Plantas/química , Podofilotoxina/química , Antivirais/química , Benzodioxóis/química , Benzodioxóis/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , Desenvolvimento de Medicamentos , Furanos/química , Furanos/farmacologia , Lignanas/farmacologia , Masoprocol/análogos & derivados , Masoprocol/química , Masoprocol/farmacologia , Masoprocol/uso terapêutico , Podofilotoxina/farmacologia , Podofilotoxina/uso terapêutico
8.
Molecules ; 25(2)2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31940776

RESUMO

Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen C. pneumoniae is tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of C. pneumoniae clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan schisandrin reverted C. pneumoniae persistence and promoted productive infection. The concomitant administration of schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection from the macrophages. The observed chemosensitization of C. pneumoniae was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia-host interactions. These data indicate that schisandrin lignans induce a phenotypic switch in C. pneumoniae, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation.


Assuntos
Bioensaio/métodos , Chlamydophila pneumoniae/fisiologia , Ciclo-Octanos/farmacologia , Lignanas/farmacologia , Macrófagos/microbiologia , Azitromicina/administração & dosagem , Azitromicina/farmacologia , Chlamydophila pneumoniae/efeitos dos fármacos , Chlamydophila pneumoniae/crescimento & desenvolvimento , Ciclo-Octanos/administração & dosagem , Ciclo-Octanos/química , Glutationa/metabolismo , Humanos , Cinética , Lignanas/administração & dosagem , Lignanas/química , Macrófagos/efeitos dos fármacos , Oxirredução , Fenótipo , Compostos Policíclicos/administração & dosagem , Compostos Policíclicos/química , Compostos Policíclicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Células THP-1
9.
Molecules ; 25(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947789

RESUMO

In this review article, the occurrence of nor-lignans and their biological activities are explored and described. Nor-lignans have proven to be present in several different families also belonging to chemosystematically distant orders as well as to have many different beneficial pharmacological activities. This review article represents the first one on this argument and is thought to give a first overview on these compounds with the hope that their study may continue and increase, after this.


Assuntos
Lignanas/química , Lignanas/uso terapêutico , Plantas/química , Animais , Humanos
10.
J Sci Food Agric ; 100(5): 1842-1851, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31802495

RESUMO

Extra virgin olive oil (EVOO), a key component of the Mediterranean diet, has aroused interest in recent years due to its health properties. Nuclear magnetic resonance (NMR) spectroscopy is an appropriate tool for the accurate quantification of minor compounds in complex food matrices, such as polyphenols in olive oil. Flavonoids, lignans, secoiridoids and phenolic acids and alcohols in EVOO have been identified and quantified by NMR. This review provides an overview of the major developments in the structural elucidation of polyphenol compounds in EVOO. © 2019 Society of Chemical Industry.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Azeite de Oliva/química , Polifenóis/química , Flavonoides/química , Iridoides/química , Lignanas/química
11.
Nat Prod Res ; 34(2): 197-203, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30856343

RESUMO

Two new norneolignans, (7S,8R)-3-methoxy-3',4,9-trihydroxy-4',7-epoxy-8,3'-neolignane-1'-carboxylic acid (1) and (7R,8R)-3-methoxyl-4,9-dihydroxy-3':7,4':8-diepoxyneolignan-1'-carboxylic acid methyl ester (2) were isolated from Callicarpa kwangtungensis, together with ten known compounds, genistin (3), daidzin (4), silybin A (5), isosilybin A (6), isosilybin B (7), p-hydroxybenzaldehyde (8), syringic acid (9), lanceolatin A (10), icariside C5 (11), and (3S,6E,10R)-10-ß-D-glucopyranosyloxy-3,11-dihydroxy-3,7,11-trimethyldodeca-1,6-diene (12). Compounds 1 and 2 were evaluated for their effects on the inhibition of nitric oxide (NO) production in lipopolysaccharide induced RAW264.7 cells. Compounds 1 and 2 exhibited inhibitory activity with IC50 values of 31.45 ± 0.38 and 40.72 ± 0.54 µM, respectively.


Assuntos
Callicarpa/química , Lignanas/isolamento & purificação , Óxido Nítrico/antagonistas & inibidores , Animais , Concentração Inibidora 50 , Lignanas/análise , Lignanas/química , Lignanas/farmacologia , Lipopolissacarídeos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Células RAW 264.7
12.
Nat Prod Res ; 34(3): 390-397, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30600696

RESUMO

Twenty-seven compounds, including a new diarypropane and two new lignans were isolated from the twigs and leaves of Endocomia macrocoma. Their structures were elucidated by spectroscopic analysis. Cytotoxicity evaluation of the new compounds against five human tumor lines showed no inhibitory effects.[Formula: see text].


Assuntos
Lignanas/isolamento & purificação , Myristicaceae/química , Propano/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lignanas/química , Lignanas/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Folhas de Planta/química , Propano/química , Propano/farmacologia
13.
Nat Prod Res ; 34(3): 359-368, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30600708

RESUMO

Phytochemical investigation of the roots of Solanum melongena L. resulted in the isolation of ten terpenes and sixteen lignans, including a new triterpene saponin, officinoterpenoside E (1) and twenty-five known compounds (2-26). All compounds were firstly isolated from S. melongena except 2, 13, 21, 22. The structures of these compounds were determined by 1 D and 2 D NMR spectra referring to the literatures, together with high-resolution mass spectrometric analysis. All compounds were evaluated for the cytotoxicity against three cancer cell lines (HepG2, Hela, and MCF-7) in vitro. The results showed that compounds 1, 6, 20, 25 and 26 exhibited moderate cytotoxicity against HepG2, Hela and MCF-7 cells with IC50 values in the range of 16.8 ± 1.7 to 29.1 ± 1.9 µM. Therefore, these terpenoids and lignans may have potential biological activity, and also seemed to be of great chemotaxonomic value for S. melongena.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Citotoxinas/isolamento & purificação , Lignanas/isolamento & purificação , Raízes de Plantas/química , Solanum melongena/química , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Citotoxinas/farmacologia , Células HeLa , Células Hep G2 , Humanos , Lignanas/química , Lignanas/farmacologia , Células MCF-7 , Estrutura Molecular , Compostos Fitoquímicos/análise , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Triterpenos/análise , Triterpenos/farmacologia
14.
Nat Prod Res ; 34(4): 456-463, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30445834

RESUMO

The phytochemical investigation on the twigs and leaves of Archidendron clypearia (Jack) I.C.N. led to the isolation of three pairs of furolactone-type lignans enantiomers, including a pair of new compounds (1R,5S,6S)-Kachiranol (1a) and (1S,5R,6R)-Kachiranol (1b) and four known compounds (2a/2b and 3a/3b). Separation of the furolactone-type lignans enantiomeric mixtures was achieved using chiral HPLC for the first time. Their structures were determined by spectroscopic analysis and comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All optical pure compounds were evaluated for their inhibitory effects on ß-amyloid aggregation by ThT assay. Among them, the inhibitory activity of the compound 1b (71.1%) was higher than the positive control (61.0%) and other compounds. In addition, molecular dynamics and molecular docking were employed to explore the binding relationship between the ligand and the receptor.


Assuntos
Fabaceae/química , Lignanas/química , Compostos Fitoquímicos/análise , Agregação Patológica de Proteínas/tratamento farmacológico , Peptídeos beta-Amiloides/efeitos dos fármacos , Dicroísmo Circular , Lignanas/isolamento & purificação , Lignanas/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Agregação Patológica de Proteínas/prevenção & controle , Estereoisomerismo
15.
Nat Prod Res ; 34(2): 225-232, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30580619

RESUMO

One new aryldihydronaphthalene-type lignan (1) together with eight known lignans (2-4, 7-11) as well as two caffeic-acid dimers (5, 6) were isolated from an ethanol extract of the whole plant of Corispermum mongolicum Iljin (Chenopodiaceae). The chemical structures of these compounds were determined from 1D and 2D NMR and HR-ESI-MS spectra, and results were compared with data from the literature. This study is the first demonstration of nine compounds (2 and 4-11) isolated from the Chenopodiaceae family, with one of these (3) from the genus Corispermum. Anti-inflammatory effects of the isolated compounds were evaluated in terms of inhibition of production of nitric oxide, tumour necrosis factor-α, and interleukin-6 in lipopolysaccharide-induced RAW 264.7 cells.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Chenopodiaceae/química , Lignanas/isolamento & purificação , Extratos Vegetais/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Chenopodiaceae/metabolismo , Interleucina-6/biossíntese , Lignanas/química , Lignanas/farmacologia , Lipopolissacarídeos , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/efeitos dos fármacos
16.
Nat Prod Res ; 34(3): 329-334, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30587031

RESUMO

A new dibenzocyclooctdiene (1), and a new eupodienone (2) type lignans were isolated along with five known analogues from the whole plant of Gymnotheca involucrata Pei. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis. Bioassay results showed that compounds 1 and 2 exhibited no antimicrobial activity against four Gram-positive bacterial strains and four Gram-negative bacteria at the concentration of 1 mg/mL.


Assuntos
Lignanas/isolamento & purificação , Saururaceae/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Lignanas/química , Estrutura Molecular , Análise Espectral/métodos
17.
Molecules ; 25(1)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861910

RESUMO

In the search for new compounds with antileishmanial activity, we synthesized a triazole hybrid analogue of the neolignans grandisin and machilin G (LASQUIM 25), which was previously found highly active against both promastigotes and intracellular amastigote forms of Leishmania amazonensis. In this work, we investigated the leishmanicidal effects of LASQUIM 25 to identify the mechanisms involved in the cell death of L. amazonensis promastigotes. Transmission electron microscopy (TEM) analysis showed marked effects of LASQUIM 25 (IC50 = 7.2 µM) on the morphology of promastigote forms, notably on mitochondria. The direct action of the triazole derivative on the parasite was noticed over time from 2 h to 48 h, and cells displayed several ultrastructural alterations characteristic of apoptotic cells. Also, flow cytometric analysis (FACS) after TMRE staining detected changes in mitochondrial membrane potential after LASQUIM 25 treatment (64.83% labeling versus 83.38% labeling in nontreated cells). On the other hand, FACS after PI staining in 24 h-treatment showed a slight alteration in the integrity of the cell membrane, a necrotic event (16.76% necrotic cells versus 3.19% staining in live parasites). An abnormal secretion of lipids was observed, suggesting an exocytic activity. Another striking finding was the presence of autophagy-related lysosome-like vacuoles, suggesting an autophagic cell death that may arise as consequence of mitochondrial stress. Taken together, these results suggest that LASQUIM 25 leishmanicidal mechanisms involve some degree of mitochondrial dysregulation, already evidenced by the treatment with the IC50 of this compound. This effect may be due to the presence of a methylenedioxy group originated from machilin G, whose toxicity has been associated with the capacity to generate electrophilic intermediates.


Assuntos
Antiprotozoários , Leishmania mexicana/metabolismo , Lignanas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Triazóis , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Lignanas/química , Lignanas/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Triazóis/química , Triazóis/farmacologia
18.
Molecules ; 25(1)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861927

RESUMO

Anwuligan, a natural 2,3-dibenzylbutane lignan from the nutmeg mace of Myristica fragans, has been proved to possess a broad range of pharmacological effects. A rapid, simple, and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been established and successfully applied to the study of pharmacokinetics and tissue distribution of anwuligan after intravenous or intragastric administration. Sample preparation was carried out through a liquid-liquid extraction method with ethyl acetate as the extraction reagent. Arctigenin was used as the internal standard (IS). A gradient program was employed with a mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile. The mass spectrometer was operated in a positive ionization mode with multiple reaction monitoring. The transitions for quantification were m/z 329.0→205.0 for anwuligan and m/z 373.0→137.0 for IS, respectively. Calibration curves were linear over the ranges of 0.5-2000 ng/mL for both plasma samples and tissue samples (r > 0.996). The absolute bioavailability is 16.2%, which represented the existing of the obvious first-pass effect. An enterohepatic circulation was found after the intragastric administration. Anwuligan could be distributed rapidly and widely in different tissues and maintained a high concentration in the liver. The developed and validated LC-MS/MS method and the pharmacokinetic study of anwuligan would provide reference for the future investigation of the preclinical safety of anwuligan as a candidate drug.


Assuntos
Lignanas , Fígado/metabolismo , Myristica/química , Administração Intravenosa , Animais , Lignanas/química , Lignanas/farmacocinética , Lignanas/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
19.
Chin J Nat Med ; 17(12): 945-952, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31882050

RESUMO

Twenty-one lignans including three new ones (1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1D and 2D NMR analysis. These compounds were evaluated for their cytotoxic and anti-HIV activities. The new secoisolariciresinol dimethyl ether acetate (13) exhibited anti-HIV-1 activity with an IC50 value of 5.27 µmol·L-1 and a selective index (SI) value of 2.2. The known arylnaphthalene lignan procumbenoside A (3) and diphyllin (8) demonstrated inhibitory activity against HIV-1 with IC50 values of 4.95 (SI > 6.2) and 0.38 µmol·L-1 (SI = 5.3), respectively.


Assuntos
Fármacos Anti-HIV/química , HIV-1/efeitos dos fármacos , Adhatoda/química , Lignanas/química , Extratos Vegetais/química , Fármacos Anti-HIV/isolamento & purificação , China , Cromatografia Líquida de Alta Pressão , Lignanas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Componentes Aéreos da Planta/química
20.
J Agric Food Chem ; 67(51): 14152-14159, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31747278

RESUMO

While lignans and their biogenetic precursors can have various health benefits, the poor liposolubilities of such phenolic systems have restricted their application as antioxidants in the food industry. The research reported here was aimed at addressing these matters through derivatizing certain forms of such compounds and then assessing their properties as potential nutraceuticals. In particular, crude flaxseed lignan was purified to afford secoisolariciresinol diglucoside (SDG, 1) that was then subjected to structural modification. By such means, the SDG long-chain fatty acid esters 4-9 and 11-13, the fully acetylated SDG 10, secoisolariciresinol (SECO, 2), and anhydrosecoisolariciresinol (ASECO, 14) were obtained. The antioxidant activities of these derivatives were determined while their permeability properties were evaluated. Such studies revealed that certain SDG derivatives possessing useful liposolubilities also retained their antioxidative properties, as well as being capable of permeating Caco-2 cell monolayers while being nontoxic to them. SDG fatty acid esters 4-9 and 11-13 could be developed into emulsifiers with enhanced health benefits, especially considering their improved antioxidative (ca. <11 000 µmol Trolox/g) and permeability properties. This study thus highlights strategies for the structural modification of SDG so as to generate derivatives with superior properties in terms of their utility in the food and pharmaceutical industries.


Assuntos
Antioxidantes/química , Linho/química , Lignanas/química , Extratos Vegetais/química , Sementes/química , Antioxidantes/metabolismo , Células CACO-2 , Humanos , Lignanas/metabolismo , Estrutura Molecular , Permeabilidade , Extratos Vegetais/metabolismo , Solubilidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA