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1.
Food Chem ; 301: 125207, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377621

RESUMO

Recent studies have shown that the high susceptibility of flaxseed oil nanoemulsions to lipid oxidation limits their incorporation into functional foods and beverages. For this reason, the impact of various flaxseed phenolic extracts on the physical and oxidative stability of flaxseed oil nanoemulsions was investigated. Flaxseed lignan extract (FLE) and secoisolariciresinol (SECO) exhibited antioxidant activity whereas secoisolariciresinol diglucoside (SDG) and p-coumaric acid (CouA) exhibited prooxidant activity in the flaxseed oil nanoemulsions. The antioxidant potential of flaxseed phenolics in the nanoemulsions was as follows: SECO < CouA < SDG ≈ FLE. Moreover, the antioxidant/prooxidant activity of the phenolics was also related to their free radical scavenging activity and partitioning in the nanoemulsions. Our results suggested that both SECO and FLE were good plant-based antioxidants for improving the stability of flaxseed oil nanoemulsions.


Assuntos
Butileno Glicóis/química , Emulsões/química , Linho/química , Lignanas/química , Óleo de Semente do Linho/química , Polifenóis/química , Antioxidantes/química , Glucosídeos/química , Hidrólise , Nanoestruturas/química , Oxirredução , Extratos Vegetais/química , Água/química
2.
AAPS PharmSciTech ; 20(6): 247, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286321

RESUMO

We aim to describe the influence of principal ingredients of Wuzhi capsule, schisandrin A (SIA) and schisantherin A (STA), on the pharmacokinetics of cyclosporin A (CsA) and to quantify the herb-drug interactions (HDIs) between SIA, STA, and CsA. CsA is a first-line immunosuppressant for anti-rejection therapy after solid organ transplantation, while narrow therapeutic window associated with strong hepatotoxicity largely limited its use. Wuzhi capsule, a liver-protective drug, was approved for coadministration with CsA to reduce the hepatotoxicity. There are few studies exploring HDIs of CsA when coadministered with Wuzhi capsule. The essential adjusted physicochemical data and pharmacokinetic parameters of SIA, STA, and CsA were collected. Then physiologically based pharmacokinetic (PBPK) models of SIA, STA, and CsA were built and verified in healthy subjects using Simcyp respectively. The refined PBPK models were used to estimate potential HDIs between CsA and SIA, STA. The simulated plasma concentration-time curves of CsA, SIA, and STA were in good accordance with the observed profiles respectively. CsA pharmacokinetics were improved after coadministration. After a single dose and multiple doses, the area under the plasma concentration-time curve (AUC) of CsA was increased by 47% and 226% when coadministered with STA, respectively, and by 8% and 36% when coadministered with SIA, respectively. PBPK models sufficiently described the pharmacokinetics of CsA, SIA, and STA. Compared with SIA, STA inhibited CsA metabolism to a greater extent. Our result revealed the dose of CsA can be reduced to maintain similar profile when used concomitantly with Wuzhi capsule.


Assuntos
Ciclo-Octanos/administração & dosagem , Ciclosporina/farmacocinética , Dioxóis/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Imunossupressores/farmacocinética , Lignanas/administração & dosagem , Compostos Policíclicos/administração & dosagem , Adulto , Ciclo-Octanos/química , Ciclosporina/administração & dosagem , Dioxóis/química , Interações Ervas-Drogas , Humanos , Imunossupressores/administração & dosagem , Lignanas/química , Masculino , Compostos Policíclicos/química
3.
Chem Pharm Bull (Tokyo) ; 67(7): 640-647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257319

RESUMO

Neuroinflammation manifested by over-activation of microglial cells plays an essential role in neurodegenerative diseases. Short-term activation of microglia can be beneficial, but chronically activated microglia can aggravate neuronal dysfunction possibly by secreting potentially cytotoxic substances such as tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO), which can result in dysfunction and death of neurons. Therefore inhibiting over-activation of microglia and the production of cytotoxic intermediates may become an effective therapeutic approach for neuroinflammation. In this paper, we review our continuous research on natural inhibitors of over-activated microglia from traditional herbals, including flavonoids, lignans, sesquiterpene coumarins, and stilbenes.


Assuntos
Produtos Biológicos/química , Microglia/metabolismo , Animais , Produtos Biológicos/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Lignanas/química , Lignanas/farmacologia , Microglia/citologia , Microglia/efeitos dos fármacos , Óxido Nítrico/biossíntese , Estilbenos/química , Estilbenos/farmacologia , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/metabolismo
4.
Chem Pharm Bull (Tokyo) ; 67(9): 966-976, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31257308

RESUMO

Honokiol, a biphenolic neolignan isolated from Magnolia officinalis, was reported to have a promising anti-inflammatory activity for the treatment of various diseases. There are many efforts on the synthesis and structure-activity relationship of honokiol derivatives. However, regioselective O-alkylation of honokiol remains a challenge and serves as a tool to provide not only some derivatives but also chemical probes for target identification and mode of action. In this study, we examined the reaction condition for regioselective O-alkylation, in which C2 and C4'-alkylated analogs of honokiol were synthesized and evaluated for inhibitory activity on nitric oxide production and cyclooxygenase-2 expression. Furthermore, we successfully synthesized a potential photoaffinity probe consisting of biotin and benzophenone based on a C4'-alkylated derivative.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Compostos de Bifenilo/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inflamação/tratamento farmacológico , Lignanas/farmacologia , Alquilação , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Compostos de Bifenilo/síntese química , Compostos de Bifenilo/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Humanos , Inflamação/metabolismo , Lignanas/síntese química , Lignanas/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Estereoisomerismo
5.
Phytochemistry ; 165: 112047, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203102

RESUMO

Four undescribed lignans and two undescribed sesquiterpenic acids, together with three known compounds (hypochoeroside C, hypochoeroside D, and 5-O-caffeoylshikimic acid) were isolated from the roots of Hypochaeris radicata subsp. neapolitana (Asteraceae, Cichorieae). The lignans were identified as 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranosyl-2'-O-methacrylate, (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-7,8,7',8'-tetrahydronaphtho [8,8'-c]furan-1(3H)-one, and (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-8'-(hydroxymethyl)-7,8,7',8'-tetrahydronaphthalen-8-carboxylic acid. The two sesquiterpenic acids were identified as the ring open precursors of hypochoerosides C and D. Structures were elucidated using NMR and HRMS. Absolute configurations of (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-7,8,7',8'-tetrahydronaphtho [8,8'-c]furan-1(3H)-one and (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-8'-(hydroxymethyl)-7,8,7',8'-tetrahydronaphthalen-8-carboxylic acid were determined using electronic circular dichroism (ECD) spectroscopy. 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside was evaluated for its anti-proliferative activity against myeloma cell lines MM1S, U266, and NCI-H929 and showed cytotoxicity at 100 mM against MM1S strain. No neurotoxicity was observed for major compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, hypochoeroside C, and hypochoeroside D in a fluorescence assay measuring neurite outgrowth in dorsal root ganglion (DRG) neurons. Additionally, compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, hypochoeroside C, hypochoeroside D, and hypochoerosidic acid D were quantified in unstressed and drought-stressed plants using HPLC-DAD. Drought-stressed plants were found to contain lower concentrations of the lignan 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside and sesquiterpene lactone hypochoeroside C.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Lactonas/farmacologia , Lignanas/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Mieloma Múltiplo/patologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade
6.
Chem Biol Interact ; 309: 108675, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31150632

RESUMO

Liver fibrosis is a progression of chronic liver disease with lacks effective therapies at present. Schisandrin B (Sch B), a bioactive compound extracted from the traditional Chinese medicine Schisandra chinensis, was reported to benefit liver diseases. This study aimed to investigate the therapeutic effects and molecular mechanisms of Sch B against CCl4-induced liver fibrosis in rats. RNA sequencing and transcriptome analysis were performed collaboratively, including analysis of differential gene expression, gene ontology (GO) analysis, pathway analysis and pathway-act-network analysis. The results demonstrated that Sch B effectively alleviated CCl4-induced liver damage and fibrosis in rats, as evidenced by improved liver function and decreased extracellular matrix deposition. Furthermore, 4440 (1878 up-regulated, 2562 down-regulated) genes in the model group versus (vs) normal group, 4243 (2584 up-regulated, 1659 down-regulated) genes in Sch B-treated group vs model group were identified as differentially expressed genes (DEGs). Subsequently, GO analysis revealed that DEGs were mainly enriched in metabolism, oxidation-reduction, endoplasmic reticulum stress and apoptosis-related biological processes. Pathway analysis suggested that Sch B up-regulated cytochrome P450 drug metabolism, PPAR signaling pathways, and down-regulated glutathione metabolism pathways. In addition, the regulatory patterns of Sch B on key genes and pathways were also confirmed. In conclusion, our study demonstrated Sch B alleviated CCl4-induced liver fibrosis by multiple modulatory mechanisms, which provide new clues for further pharmacological study of Sch B.


Assuntos
Lignanas/farmacologia , Cirrose Hepática/patologia , Fígado/metabolismo , Compostos Policíclicos/farmacologia , Transcriptoma , Animais , Apoptose/efeitos dos fármacos , Tetracloreto de Carbono/toxicidade , Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , Ciclo-Octanos/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Perfilação da Expressão Gênica , Lignanas/química , Lignanas/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Masculino , Medicina Tradicional Chinesa , Compostos Policíclicos/química , Compostos Policíclicos/uso terapêutico , RNA/química , RNA/isolamento & purificação , RNA/metabolismo , Ratos , Ratos Wistar , Schisandra/química , Schisandra/metabolismo , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos
7.
Fitoterapia ; 137: 104190, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31163199

RESUMO

The genus Tripterygium belongs to the family Celastraceae, and contains three species, i.e. Tripterygium wilfordii Hook. F, Tripterygium hypoglaucum (Levl.) Hutch. and Tripterygium regelii Sprague et Takeda. All three species are reported to have excellent medicinal properties that help to cure rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus and widely used as a folk medicine in China. Phytochemical studies have led to discovering more than 500 secondary metabolites in this genus, including five main types: sesquiterpenoids, diterpenes, triterpenoids, flavonoids, lignans. This work provides structurally grouping statistic of 198 secondary metabolites of Tripterygium species published from 2008 to the present, as well as pharmacological knowledges in the past five years. The information will be helpful for developing the new discoveries of medicinal value related to the genus Tripterygium.


Assuntos
Tripterygium/química , Tripterygium/classificação , Animais , Anti-Inflamatórios/química , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Antivirais/química , Diterpenos/química , Flavonoides/química , Humanos , Imunossupressores/química , Lignanas/química , Estrutura Molecular , Fármacos Neuroprotetores/química , Compostos Fitoquímicos/química , Metabolismo Secundário , Sesquiterpenos/química , Triterpenos/química
8.
J Agric Food Chem ; 67(28): 7880-7885, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31250636

RESUMO

Ninety-two new 9-norlignan derivatives containing more effective compounds against both cancer and insect cells than lead compounds were synthesized. Against HeLa cells, 7-(3,4-dimethoxyphenyl)-7'-(3'-hydroxy-4'-methoxyphenyl) derivative 63 (IC50 = 0.9 ± 0.2 µM) was to be around 6-fold more potent than lead compound 5. Moreover, against HL-60 cells, 7-(4-trifluoromethylphenyl)-7'-(3'/4'-hydroxyphenyl) derivatives 78 and 79 (IC50 = 2.2 ± 0.4 µM and 2.4 ± 0.6 µM) were 3-fold more potent than lead compound 5. Furthermore, against Sf9 cells from the common cutworm, the 7-(4-trifluoromethylphenyl) derivatives bearing electron-withdrawing groups 76-96 showed a wider range of activity (around 20-fold difference), giving valuable information on the structure-activity relationship. The 7-(4-trifluoromethylphenyl)-7'-(2'/3'-hydroxyphenyl) derivatives 77 and 78 (IC50 = 4.7 ± 0.6 µM and 4.9 ± 0.9 µM) had around 2-fold higher activity against Sf9 cells than lead compound 5. The 7-(4-trifluoromethylphenyl)-7'-(3'-hydroxyphenyl) derivative 78 was also effective against mosquito NIAS-AcAl-2 cells with an IC50 value of 5.4 ± 0.3.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Lignanas/química , Lignanas/farmacologia , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Culicidae , Desenho de Drogas , Células HL-60 , Células HeLa , Humanos , Lignanas/síntese química , Spodoptera , Relação Estrutura-Atividade
9.
Chem Biol Interact ; 308: 339-349, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170387

RESUMO

Magnolol, the most abundant bioactive constituent of the Chinese herb Magnolia officinalis, has been found with multiple biological activities, including anti-oxidative, anti-inflammatory and enzyme-regulatory activities. In this study, the inhibitory effects and inhibition mechanism of magnolol on human carboxylesterases (hCEs), the key enzymes responsible for the hydrolytic metabolism of a variety of endogenous esters as well as ester-bearing drugs, have been well-investigated. The results demonstrate that magnolol strongly inhibits hCE1-mediated hydrolysis of various substrates, whereas the inhibition of hCE2 by magnolol is substrate-dependent, ranging from strong to moderate. Inhibition of intracellular hCE1 and hCE2 by magnolol was also investigated in living HepG2 cells, and the results showed that magnolol could strongly inhibit intracellular hCE1, while the inhibition of intracellular hCE2 was weak. Inhibition kinetic analyses and docking simulations revealed that magnolol inhibited both hCE1 and hCE2 in a mixed manner, which could be partially attributed to its binding at two distinct ligand-binding sites in each carboxylesterase, including the catalytic cavity and the regulatory domain. In addition, the potential risk of the metabolic interactions of magnolol via hCE1 inhibition was predicted on the basis of a series of available pharmacokinetic data and the inhibition constants. All these findings are very helpful in deciphering the metabolic interactions between magnolol and hCEs, and also very useful for avoiding deleterious interactions via inhibition of hCEs.


Assuntos
Compostos de Bifenilo/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Lignanas/metabolismo , Sítios de Ligação , Biocatálise , Compostos de Bifenilo/química , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Domínio Catalítico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Células Hep G2 , Humanos , Hidrólise , Cinética , Lignanas/química , Simulação de Acoplamento Molecular
10.
Phytochemistry ; 164: 102-110, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31112925

RESUMO

A bioassay-guided chemical investigation on the ethyl acetate extract of the stems of Herpetospermum pedunculosum led to the isolation and identification of 22 lignans including 6 previously undescribed ones, herpetosiols A-F. Their structures including stereochemistries were elucidated by analysis of NMR, HRMS and ECD data. The in vitro cytotoxic activities of all isolates were studied against human gastric carcinoma SGC7901, lung carcinoma A549, breast carcinoma MDA-MB-231 and hepatocellular carcinoma HepG2 cell lines. Among them, eight lignans exhibited anti-proliferative effects against four tumor cell lines with IC50 ranging from 1.7 ±â€¯0.1 to 32.6 ±â€¯1.1 µM. Hedyotol-B displayed potent inhibitory effect with IC50 values of 1.7 ±â€¯0.1 µM against SGC7901 and 6.1 ±â€¯0.5 µM against A549, respectively.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cucurbitaceae/química , Lignanas/farmacologia , Caules de Planta/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Conformação Molecular , Relação Estrutura-Atividade
11.
Chem Biol Interact ; 307: 82-90, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31047918

RESUMO

Honokiol (HKL) is a natural low-molecular-weight biphenolic compound derived from the bark of magnolia trees. Previous studies indicate that HKL exerts potent cardioprotective effects on ischemia/reperfusion (I/R) injury; however, evidence of the further relationship between HKL posttreatment and myocardial I/R injury has not been clearly found. In our study, we explored the protective effect of HKL post treatment on myocardial I/R injury in C57BL/6 mice. We also demonstrated that HKL significantly reduced cellular reactive oxygen species production and attenuated mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation (H/R). In addition, HKL was found to enhance autophagy during I/R or H/R; these effects could be partially blocked by the autophagic flux inhibitor chloroquine. Moreover, our results suggested that enhanced autophagic flux is associated with the Akt signaling pathway. Collectively, our results indicate that HKL posttreatment alleviates myocardial I/R injury and suggest a critical cardioprotective role of HKL in promoting autophagic flux.


Assuntos
Autofagia , Compostos de Bifenilo/uso terapêutico , Lignanas/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Cloroquina/farmacologia , Modelos Animais de Doenças , Lignanas/química , Lignanas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
12.
Eur J Med Chem ; 176: 162-174, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31103897

RESUMO

Chagas disease is a neglected protozoan disease that affects more than eight million people in developing countries. Due to the limited number and toxicity profiles of therapies in current use, new drugs are urgently needed. In previous studies, we reported the isolation of two related antitrypanosomal neolignans from Nectandra leucantha (Lauraceae). In this work, a semi-synthetic library of twenty-three neolignan derivatives was prepared to explore synthetically accessible structure activity relationships (SAR) against Trypanosoma cruzi. Five compounds demonstrated activity against trypomastigotes (IC50 values from 8 to 64 µM) and eight showed activity against intracellular amastigotes (IC50 values from 7 to 16 µM). Eighteen derivatives demonstrated no mammalian cytotoxicity up to 200 µM. The phenolic acetate derivative of natural dehydrodieugenol B was effective against both parasite forms and eliminated 100% of amastigotes inside macrophages. This compound caused rapid and intense depolarization of the mitochondrial membrane potential, with decreased levels of intracellular reactive oxygen species being observed. Fluorescence assays demonstrated that this derivative affected neither the permeability nor the electric potential of the parasitic plasma membrane, an effect also corroborated by scanning electron microscopy studies. Structure-activity relationship studies (SARs) demonstrated that the presence of at least one allyl side chain on the biaryl ether core was important for antitrypanosomal activity, and that the free phenol is not essential. This set of neolignan derivatives represents a promising starting point for future Chagas disease drug discovery studies.


Assuntos
Anisóis/farmacologia , Lignanas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Anisóis/síntese química , Anisóis/química , Anisóis/toxicidade , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Humanos , Lignanas/síntese química , Lignanas/química , Lignanas/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Testes de Sensibilidade Parasitária , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Tripanossomicidas/toxicidade , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/metabolismo
13.
J Enzyme Inhib Med Chem ; 34(1): 999-1009, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31072143

RESUMO

This study explored the possible bioactive ingredients and target protein of Rostellularia procumbens (L.) Nees. The results of optical turbidimetry revealed that the ethyl acetate extraction obtained from R. procumbens (L.) Nees could inhibit platelet aggregation. Gene chip was used to investigate differentially expressed genes. According to the results of the gene chip, the targets of compounds isolated from the ethyl acetate extraction were predicted by network pharmacology. Computational studies revealed that chinensinaphthol methyl ether and neojusticin B may target the integrin αIIbß3 protein. The results of Prometheus NT.48 and microscale thermophoresis suggested that the molecular interactions between the two compounds with purified integrin αIIbß3 protein in the optimal test conditions were coherent with the docking results. To our best knowledge, this is the first report to state that chinensinaphthol methyl ether and neojusticin B target the integrin αIIbß3 protein.


Assuntos
Acanthaceae/química , Derivados de Benzeno/farmacologia , Dioxolanos/farmacologia , Éteres/farmacologia , Lignanas/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Derivados de Benzeno/química , Derivados de Benzeno/isolamento & purificação , Dioxolanos/química , Dioxolanos/isolamento & purificação , Relação Dose-Resposta a Droga , Éteres/química , Éteres/isolamento & purificação , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/química , Inibidores da Agregação de Plaquetas/isolamento & purificação , Testes de Função Plaquetária , Relação Estrutura-Atividade
14.
Chem Biol Interact ; 307: 51-57, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31026422

RESUMO

Nasopharyngeal carcinoma (NPC) is a head and neck epithelial malignancy with high prevalence and represents a significant disease burden. Eudesmin is a natural lignin that has been reported to exhibit antitumor effect on lung cancer. However, the effect of eudesmin on NPC has not been investigated. The aim of the present study was to evaluate the role of eudesmin in NPC and to explore the underlying mechanism. The NPC cell lines CNE-1 and HONE-1 were treated with eudesmin for 48 h. Cell viability was measured using MTT assay. Cell apoptosis was detected using flow cytometry. The expression levels of enhancer of zeste homolog 2 (EZH2), Akt, and p-Akt were measured using Western blot analysis. We found that eudesmin inhibited cell viability and induced cell apoptosis of NPC cell lines in a dose-dependent manner. Eudesmin suppressed the expression of EZH2 and blocked the activation of Akt signaling pathway. Inhibition of Akt signaling pathway caused significant decrease in EZH2 expression. Moreover, knockdown of EZH2 attenuated the effects of Akt overexpression on cell viability and apoptosis in NPC cells. In conclusion, eudesmin exhibited antitumor activity via downregulating EZH2 expression through the inhibition of Akt signaling pathway. Eudesmin could be developed as a new pharmacologic approach for NPC treatment.


Assuntos
Antineoplásicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Furanos/farmacologia , Lignanas/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Furanos/química , Humanos , Lignanas/química , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
J Microbiol Biotechnol ; 29(4): 571-576, 2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-30955254

RESUMO

Microenvironmental stress, which is naturally observed in solid tumors, has been implicated in anticancer drug resistance. This tumor-specific stress causes the degradation of topoisomerase IIα, rendering cells resistant to topoisomerase IIα-targeted anticancer agents. In addition, microenvironmental stress can induce the overexpression of 78kDa glucose regulated protein (GRP78), which can subsequently block the activation of apoptosis induced by treatment with anticancer agents. Therefore, inhibition of topoisomerase IIα degradation and reduction in GRP78 expression may be effective strategies for inhibiting anticancer drug resistance. In this study, we investigated the active compound arctigenin, which inhibited microenvironmental stress-induced etoposide resistance in HT-29 cells. Arctigenin was also highly toxic to etoposide-resistant HT-29 cells, with an IC50 value of 10 µM for colony formation. We further showed that arctigenin inhibited the degradation of topoisomerase IIα and reduced the expression of GRP78. Thus, these results suggest that arctigenin is a novel therapeutic agent that inhibits resistance to etoposide associated with microenvironmental stress conditions.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Etoposídeo/farmacologia , Furanos/antagonistas & inibidores , Células HT29/efeitos dos fármacos , Lignanas/antagonistas & inibidores , Estresse Fisiológico , Microambiente Tumoral/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , DNA Topoisomerases Tipo II , Furanos/química , Células HT29/citologia , Proteínas de Choque Térmico/metabolismo , Humanos , Lignanas/química
17.
Molecules ; 24(7)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934777

RESUMO

Lignans from Schisandra chinensis (Turcz.) Baill can ameliorate cognitive impairment in animals with Alzheimer's disease (AD). However, the metabolism of absorbed ingredients and the potential targets of the lignans from S. chinensis in animals with AD have not been systematically investigated. Therefore, for the first time, we performed an in-vivo ingredient analysis and implemented a target-network pharmacology strategy to assess the effects of lignans from S. chinensis in rats with AD. Ten absorbed prototype constituents and 39 metabolites were identified or tentatively characterized in the plasma of dosed rats with AD using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Based on the results of analysis of the effective constituents in vivo, the potential therapeutic mechanism of the effective constituents in the rats with AD was investigated using a target-network pharmacology approach and independent experimental validation. The results showed that the treatment effects of lignans from S. chinensis on cognitive impairment might involve the regulation of amyloid precursor protein metabolism, neurofibrillary tangles, neurotransmitter metabolism, inflammatory response, and antioxidant system. Overall, we identified the effective components of lignans in S. chinensis that can improve the cognitive impairment induced by AD and proposed potential therapeutic metabolic pathways. The results might serve as the basis for a fundamental strategy to explore effective therapeutic drugs to treat AD.


Assuntos
Cromatografia Líquida de Alta Pressão , Lignanas/química , Lignanas/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Schisandra/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Biomarcadores , Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , Redes e Vias Metabólicas , Estrutura Molecular , Neurônios/metabolismo , Neurotransmissores/metabolismo , Compostos Policíclicos/química , Compostos Policíclicos/farmacologia , Ratos
18.
Molecules ; 24(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30978936

RESUMO

The 13 research articles/communications, six reviews, and one perspective that comprise this Special Issue on Lignans, highlight the most recent research and investigations into this diverse and important class of bioactive natural products [...].


Assuntos
Produtos Biológicos/química , Lignanas/química , Produtos Biológicos/classificação , Humanos , Lignanas/classificação
19.
Fitoterapia ; 135: 15-21, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30923011

RESUMO

Rhododendron micranthum is used traditionally as a remedy for the treatment of chronic bronchitis in China. To clarify the chemical basis and provide a reference for the rational use of this medicinal plant, a phytochemical study was carried out on the twigs and leaves of R. micranthum, which afforded eight new compounds (1-8) and eight known compounds (9-16). Their structures were rigorously determined by comprehensive HRESIMS, NMR and electronic circular dichroism (ECD) analyses. The anti-inflammatory activities of these compounds were evaluated. Compounds 3, 13, and 14 suppressed the transcription of the NF-κB-dependent reporter gene in LPS-induced 293T/NF-κB-luc cells at 10 µM, while no effect on cell viability was observed.


Assuntos
Anti-Inflamatórios/química , Bronquite Crônica/tratamento farmacológico , Lignanas/química , Compostos Fitoquímicos/química , Rhododendron/química , Sesquiterpenos/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , China , Genes Reporter , Células HEK293 , Humanos , Lignanas/isolamento & purificação , Lignanas/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , NF-kappa B/efeitos dos fármacos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Plantas Medicinais , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia
20.
J Pharm Biomed Anal ; 170: 153-160, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30925272

RESUMO

An effective strategy based on high-speed counter-current chromatography (HSCCC) knockout combination with HPLC-DAD-QTOF-MS/MS analysis were developed to identify minor lignans, alkaloids, and phenylpropanoid glycosides in M. officinalis. Petroleum ether/ethyl acetate/methanol/water (8:4:7:5, v/v/v/v) as solvent system was firstly selected to separate the crude extract of M. officinalis. Two major lignans, honokiol and magnolol were knocked out, and minor components were enriched. Then, five standards (honokiol, magnolol, magnocurarine, magnoflorine and acteoside) were used as examples to discuss their fragmentation patterns for structural identification. By comprehensive screening, sixteen lignans, nine alkaloids, six phenylpropanoid glycosides were unambiguously or tentatively identified by comparing their retention time, UV spectra, accurate mass and fragmentation patterns with standards or reported components. Eight of them, as far as was known, were discovered from M. officinalis for the first time. The proposed method might provide a model for the effective identification of minor components from complex herbs. Additionally, this study laid a foundation for the study of quality control, and clinical applications of M. officinalis.


Assuntos
Alcaloides/química , Glicosídeos/química , Lignanas/química , Magnolia/química , Propanóis/química , Aporfinas/química , Compostos de Bifenilo/química , Cromatografia Líquida de Alta Pressão/métodos , Glucosídeos/química , Isoquinolinas/química , Metanol/química , Fenóis/química , Espectrometria de Massas em Tandem/métodos
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