Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.688
Filtrar
1.
J Agric Food Chem ; 67(39): 10871-10879, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31517482

RESUMO

This study evaluated the effect of triterpenoids from edible mushroom Poria cocos on intestinal epithelium integrity and revealed the transcriptional regulatory pathways that underpin restorative mechanisms in the gut. Based on computational docking studies, transcriptional activation experiments and glucocorticoid receptor (GR) protein immunofluorescence localization assays in cultured cells, 16α-hydroxytrametenolic acid (HTA) was discovered as a novel GR agonist in this study. HTA ameliorates TNF-α-induced Caco-2 monolayer intestinal epithelial barrier damage and suppressed activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt), which attenuated downstream IκB and nuclear factor kappa-B (NF-κB) phosphorylation through GR activation. Moreover, HTA prevented NF-κB translocation into the nucleus and binding to its cis-element and suppressed lipopolysaccharide-induced downstream NO production and pro-inflammatory cytokines at both protein and mRNA expression levels. In conclusion, HTA from P. cocos improves intestinal barrier function through a GR-mediated PI3K/Akt/NF-κB signaling pathway and may be potentially exploited as a supportive dietary therapeutic strategy for restoring gut health.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Glucocorticoides/metabolismo , Triterpenos/farmacologia , Wolfiporia/química , Células CACO-2 , Humanos , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Mucosa Intestinal/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/genética , Fosfatidilinositol 3-Quinase/genética , Fosforilação , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/genética , Receptores de Glucocorticoides/genética , Transdução de Sinais/efeitos dos fármacos , Triterpenos/química , Verduras/química
2.
J Med Microbiol ; 68(10): 1438-1444, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385784

RESUMO

Introduction. Combretum leprosum (Combretaceae) is commonly found in the Northeast Region of Brazil and is known for several bioactivities, including antimicrobial ones. Because of increasing bacterial antibiotic resistance, natural products from several plants have been studied as putative adjuvants to antibiotic activity, including products from C. leprosum. Aims. This study was carried out to investigate the structural properties, bactericidal activity and antibiotic modifying action of the lupane triterpene 3ß,6ß,16ß-trihydroxylup-20(29)-ene (CLF1) isolated from C. leprosum Mart. leaves.Methods. The CLF1 was evaluated by the Fourier transform infrared spectroscopy method and the antibacterial activity of this compound was assayed alone and in association with antibiotics by microdilution assay.Results. Spectroscopic studies confirmed the molecular structure of the CLF1 and permitted assignment of the main infrared bands of this natural product. Microbiological assays showed that this lupane triterpene possesses antibacterial action with clinical relevance against Staphylococcus aureus. The CLF1 triterpene increased antimicrobial activity against the multidrug-resistant Escherichia coli 06 strain when associated with the antibiotics gentamicin and amikacin. Synergistic effects were observed against the S. aureus 10 strain in the presence of the CLF1 triterpene with the antibiotic gentamicin.Conclusion. In conclusion, the CLF1 compound may be useful in the development of antibacterial drugs against the aforementioned bacteria.


Assuntos
Antibacterianos/farmacologia , Combretum/química , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Brasil , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Gentamicinas/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Triterpenos/química , Triterpenos/isolamento & purificação
3.
J Agric Food Chem ; 67(37): 10330-10341, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31469960

RESUMO

Fomitopsis pinicola (Sw. Ex Fr.) Krast has been commonly used as a health food source and antitumor agent. To uncover bioactive key composition of F. pinicola, in our study, we investigated the chemical constituents of a methanol extract of F. pinicola and thirty-five lanostane-type tritetpenoids; 13 new compounds (1-13) and twenty-two known analogues (14-35) were isolated. Among them, compounds 1-9 were C30 lanostane triterpenoids and triterpene sugar esters, while compounds 10-13 were C31 triterpenoids and triterpene sugar esters. Their structures and absolute configurations were elucidated by extensive 1D, 2D NMR, MS, and IR spectra. Furthermore, cytotoxic activities of all isolates against five human tumor cell lines (HL-60, A549, SMMC-7721, MCF-7, and SW480) were evaluated. The results showed that compounds 12, 14, 17, 18, 22, and 23 displayed cytotoxic effects against five human tumor cell lines with IC50 values ranging from 3.92-28.51 µM. Meanwhile, compounds 9 and 35 exhibited selected inhibitory activities against HL-60, SMMC-7721, and MCF-7 with IC50 values in the range of 13.57-36.01 µM. Furthermore, the flow cytometry analysis revealed that compounds 17, 22, and 35 induced apoptosis in HL-60 cell lines. Their structure-activity relationships were preliminarily reported. These findings indicate the vital role of triterpenoids and their glycosides in explaining antitumor effects of F. pinicola and provide important evidence for further development and utilization of this fungus.


Assuntos
Coriolaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Verduras/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
4.
Eur J Med Chem ; 179: 667-679, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279299

RESUMO

Ovarian cancer is associated with a high percentage of recurrence of tumors and resistance to chemotherapy. Cancer stem cells (CSCs) are responsible for cancer progression, tumor recurrence, metastasis, and chemoresistance. Thus, developing CSC-targeting therapy is an urgent need in cancer research and clinical application. In an attempt to achieve potent and selective anti-CSC agents, a series of celastrol derivatives with cinnamamide chains were synthesized and evaluated for their anti-ovarian cancer activities. Most of the compounds exhibited stronger antiproliferative activity than celastrol, and celastrol derivative 7g with a 3,4,5-trimethoxycinnamamide side chain was found to be the most potent antiproliferative agent against ovarian cancer cells with an IC50 value of 0.6 µM. Additionally, compound 7g significantly inhibited the colony formation ability and reduced the number of tumor spheres. Furthermore, compound 7g decreased the percentage of CD44+, CD133+ and ALDH+ cells. Thus, compound 7g is a promising anti-CSC agent and could serve as a candidate for the development of new anti-ovarian cancer drugs.


Assuntos
Antineoplásicos/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Triterpenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Estrutura Molecular , Neoplasias Ovarianas/patologia , Relação Estrutura-Atividade , Triterpenos/síntese química , Triterpenos/química , Cicatrização/efeitos dos fármacos
5.
Phytochemistry ; 166: 112076, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351331

RESUMO

Biotransformation of lupane-type triterpenoid betulin was carried out with Mucor subtilissimus CGMCC 3.2456. Yielded nine previously undescribed hydroxylated compounds. M. subtilissimus biotransformation provided C-7, C-11, C-15 and C-24 hydroxylated compounds along with C-7 oxidized and C-28 acetylated derivatives. The structures of the metabolites were established based on extensive NMR and HR-ESI-MS data analyses. Furthermore, we found that most of the metabolites exhibited pronounced inhibitory activities on lipopolysaccharides-induced NO production in RAW264.7 cells.


Assuntos
Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Mucor/metabolismo , Triterpenos/metabolismo , Triterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Biotransformação , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Modelos Moleculares , Conformação Molecular , Óxido Nítrico/biossíntese , Células RAW 264.7 , Triterpenos/química
6.
Chem Biodivers ; 16(8): e1900325, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31290253

RESUMO

Chronic myeloid leukemia (CML) is a lethal malignancy, and the progress toward long-term survival has stagnated in recent decades. Pristimerin, a quinone methide triterpenoid isolated from the Celastraceae and Hippocrateaceae families, is well-known to exert potential anticancer activities. In this study, we investigated the effects and the mechanisms of action on CML. We found that pristimerin inhibited cell proliferation of K562 CML cells by causing G1 phase arrest. Furthermore, we demonstrated that pristimerin triggered autophagy and apoptosis. Intriguingly, pristimerin-induced cell death was restored by an autophagy inhibitor, suggesting that autophagy is cross-linked with pristimerin-induced apoptosis. Further studies revealed that pristimerin could produce excessive reactive oxygen species (ROS), which then induce JNK activation. These findings provide clear evidence that pristimerin might be clinical benefit to patients with CML.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Células K562 , Espécies Reativas de Oxigênio/metabolismo , Triterpenos/química
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.
Microb Cell Fact ; 18(1): 115, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253150

RESUMO

BACKGROUND: Ganoderic acids (GAs), derived from the medicinal mushroom Ganoderma lucidum, possess anticancer and other important pharmacological activities. To improve production of GAs, a homologous farnesyl diphosphate synthase (FPS) gene was overexpressed in G. lucidum. Moreover, the influence of FPS gene overexpression on GA production was investigated by developing the corresponding mathematical models. RESULTS: The maximum levels of total GAs and individual GAs (GA-T, GA-S, and GA-Me) in the transgenic strain were 2.76 mg/100 mg dry weight (DW), 41 ± 2, 21 ± 5, and 28 ± 1 µg/100 mg DW, respectively, which were increased by 2.28-, 2.27-, 2.62-, and 2.80-folds compared with those in the control. Transcription levels of squalene synthase (SQS) and lanosterol synthase (LS) genes during GA biosynthesis were upregulated by 2.28- and 1.73-folds, respectively, in the transgenic G. lucidum. In addition, the developed unstructured models had a satisfactory fit for the process of GA production in submerged cultures of G. lucidum. Analysis of the kinetic process showed that FPS gene overexpression had a stronger positive impact on GA production compared with its influence on cell growth. Also, FPS gene overexpression led to a higher non-growth-associated-constant ß (1.151) over the growth-associated-constant α (0.026) in the developed models. CONCLUSIONS: FPS gene overexpression is an effective strategy to improve the production of GAs in G. lucidum. The developed mathematical models are useful for developing a better GA production process in future large-scale bioreactors.


Assuntos
Proteínas Fúngicas/genética , Geraniltranstransferase/genética , Reishi/metabolismo , Triterpenos/metabolismo , Farnesil-Difosfato Farnesiltransferase/genética , Farnesil-Difosfato Farnesiltransferase/metabolismo , Proteínas Fúngicas/metabolismo , Geraniltranstransferase/metabolismo , Transferases Intramoleculares/genética , Transferases Intramoleculares/metabolismo , Cinética , Reishi/química , Reishi/enzimologia , Reishi/genética , Triterpenos/química
9.
Mar Drugs ; 17(6)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146323

RESUMO

Pharmaceutical agents for halting the progression of Parkinson's disease (PD) are lacking. The current available medications only relieve clinical symptoms and may cause severe side effects. Therefore, there is an urgent need for novel drug candidates for PD. In this study, we demonstrated the neuroprotective activity of stellettin B (SB), a compound isolated from marine sponges. We showed that SB could significantly protect SH-SY5Y cells against 6-OHDA-induced cellular damage by inhibiting cell apoptosis and oxidative stress through PI3K/Akt, MAPK, caspase cascade modulation and Nrf2/HO-1 cascade modulation, respectively. In addition, an in vivo study showed that SB reversed 6-OHDA-induced a locomotor deficit in a zebrafish model of PD. The potential for developing SB as a candidate drug for PD treatment is discussed.


Assuntos
Apoptose/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poríferos/química , Triterpenos/farmacologia , Animais , Organismos Aquáticos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Locomoção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Doença de Parkinson/tratamento farmacológico , Triterpenos/química , Triterpenos/isolamento & purificação , Peixe-Zebra
10.
J Agric Food Chem ; 67(26): 7348-7364, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31180673

RESUMO

A chemical study on the peels of the cultivated edible mushroom Wolfiporia cocos led to the isolation and identification of 47 lanostane triterpenoids including 16 new compounds (1-16). The structures of the new compounds were determined by analysis of the NMR, MS, and electronic circular dichroism (ECD) data. Compounds 1 and 2 represent new members of the family of 4,5-secolanostane triterpenes. Compound 3 is a new aromatic lanostane triterpene with an unusual methyl rearrangement from C-10 to C-6. The absolute configurations of 1 and 8 were assigned by ECD spectra calculation. All compounds were evaluated for cytotoxicity (K562, SW480, and HepG2) and glucose-uptake-stimulating effects. Compounds 23, 25, 29, and 31 showed weak inhibition on the K562 cells with IC50 in the range of 25.7 to 68.2 µM, respectively. Compounds 21, 28, and 30 increased the glucose uptake in 3T3-L1 cells by 25%, 14%, and 50% at 5 µM, respectively. In addition, compounds 14, 23, 29, 35, and 43 showed insulin-sensitizing activity by increasing the insulin-stimulated glucose uptake at 2.5 µM in 3T3-L1 adipocytes. A preliminary structure-activity relationship analysis indicates that the 6/6/6/5 ring skeleton and the double bond between C-8 and C-9 are beneficial for the glucose-uptake-stimulating and insulin-sensitizing activities. Furthermore, the alkaline-insoluble fraction mainly containing compounds 22, 24, 28, and 31 were confirmed to have hypoglycemic and hypolipidemic activity on high-fat-diet-induced obese mice. This work confirms the potential of the peels' extracts of W. cocos as a functional food or dietary supplements.


Assuntos
Glucose/metabolismo , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Wolfiporia/química , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Camundongos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificação
11.
Food Chem Toxicol ; 131: 110563, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31199992

RESUMO

Apple pomace (AP) utilised for analysis of triterpenic acids (TTAs) using HPLC-MS/MS. The methanol, ethanol and ethyl acetate extracts showed high phenolic content with significant antioxidant activity compared to chloroform and n-hexane. AP TTAs; ursolic acid, betulinic acid and maslinic acid showed potent antioxidant and enzyme inhibitory effects. The IC50 values were 13.2-30.8 µg/mL (tyrosinase), 19.6-42.5 µg/mL (xanthine oxidase) and 16.6-38.6 µg/mL (urease) for AP extracts and 8.4-25.8 µg/mL (tyrosinase), 12.6-30.2 µg/mL (xanthine oxidase) and 10.1-28.6 µg/mL (urease) for TTAs, compared to the positive controls; kojic acid (10.4 ±â€¯0.06 µg/mL), allopurinol (9.6 ±â€¯0.04 µg/mL) and thiourea (8.9 ±â€¯0.02 µg/mL) towards respective enzymes. UA showed a competitive type of inhibition for tyrosinase, while BA showed a noncompetitive type of inhibition towards xanthine oxidase. In addition, the AP extracts and TTAs exerted significant cytotoxic effects towards the proliferation of cancer cell lines. AP methanol extract (IC50 of 38.5 ±â€¯4.1, 47.1 ±â€¯3.5, 70.6 ±â€¯2.3, and 50.5 ±â€¯3.9 µg/mL) and ursolic acid (IC50 of 6.5 ±â€¯0.7, 15.5 ±â€¯1.4, 20.8 ±â€¯1.3, and 5.6 ±â€¯0.8 µg/mL) showed prominent anticancer activity on Hela, Skov-3, Caski, and NCL cancer cell lines, respectively. Thus, this study shows that the AP & TTAs could be utilized for functional food development and as a potent antioxidant, anticancer, skin whitening, and anti-urolithic agents.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Depuradores de Radicais Livres/farmacologia , Frutas/química , Malus/química , Triterpenos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Cães , Ensaios Enzimáticos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Humanos , Células Madin Darby de Rim Canino , Monofenol Mono-Oxigenase/antagonistas & inibidores , Extratos Vegetais/análise , Extratos Vegetais/química , Extração em Fase Sólida , Triterpenos/química , Triterpenos/isolamento & purificação , Urease/antagonistas & inibidores , Xantina Oxidase/antagonistas & inibidores
12.
Chem Pharm Bull (Tokyo) ; 67(6): 534-539, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155558

RESUMO

One triterpene and five triterpene glycosides, including four new compounds, have been identified in the underground parts of Glycyrrhiza bucharica, which was shown to be closely related to Glycyrrhizin-producing Glycyrrhiza species, G. uralensis, G. glabra and G. inflata, based on their chloroplast rbcL sequences. Two known compounds were identified squasapogenol and macedonoside C. The structures of four new compounds, bucharosides A, B, C, and D, were determined to be 3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucuronopyranosyl-(1→2)-ß-D-glucuronopyranosyl-22-O-α-L-rhamnopyranosyl squasapogenol, 3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucuronopyranosyl-(1→2)-ß-D-glucuronopyranosyl-macedonic acid, 3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucuronopyranosyl-(1→2)-ß-D-glucuronopyranosyl-squasapogenol, and 22-O-α-L-rhamnopyranosyl squasapogenol, respectively. Contents of these triterpene glycosides were less than 0.5% of dry weight, and no main saponin, like glycyrrhizin or macedonoside C found in other Glycyrrhiza species, was found in the underground parts of G. bucharica.


Assuntos
Glycyrrhiza/química , Extratos Vegetais/química , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glycyrrhiza/metabolismo , Espectroscopia de Ressonância Magnética , Conformação Molecular , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Tadjiquistão , Terpenos/química , Terpenos/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificação
13.
Eur J Med Chem ; 177: 302-315, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158746

RESUMO

Betulin-1,4-quinone hybrids were obtain by connecting two active structures with a linker. This strategy allows for obtaining compounds showing a high biological activity and better bioavailability. In this research, synthesis, anticancer activity and molecular docking study of betulin-1,4-quinone hybrids are presented. Newly synthesized compounds were characterized by 1H, 13C NMR, IR and HR-MS. Hybrids were tested in vitro against a panel of human cell lines including glioblastoma, melanoma, breast and lung cancer. They showed a high cytotoxic activity depending on the type of 1,4-quinone moiety and the applied tumor cell lines. It was found that cytotoxic activities of the studied hybrids were increasing against the cell line with higher NQO1 protein level, like melanoma (C-32), breast (MCF-7) and lung (A-549) cancer. Selected hybrids were tested on the transcriptional activity of the gene encoding a proliferation marker (H3 histone), a cell cycle regulators (p53 and p21) and an apoptosis pathway (BCL-2 and BAX). The obtained results suggested that the tested compounds caused a mitochondrial apoptosis pathway in A549 and MCF-7 cell lines. The molecular docking was used to examine the probable interaction between the hybrids and human NAD[P]H-quinone oxidoreductase (NQO1) protein. The computational studies showed that the type of the 1,4-quinone moiety affected the location of the compound in the active site of the enzyme. Moreover, it was shown that an interaction of 1,4-quinone fragment with the hydrophobic matrix of the active site near Tyr128, Phe178, Trp105 and FAD cofactor could explain the observed increase of TP53 gene expression.


Assuntos
Antineoplásicos/farmacologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Quinonas/farmacologia , Triterpenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Betula/química , Domínio Catalítico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/genética , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , NAD(P)H Desidrogenase (Quinona)/química , Ligação Proteica , Quinonas/síntese química , Quinonas/química , Quinonas/metabolismo , Relação Estrutura-Atividade , Triterpenos/síntese química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/metabolismo , Proteína Supressora de Tumor p53/genética
14.
Chem Pharm Bull (Tokyo) ; 67(6): 604-608, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155567

RESUMO

Two new triterpene glycosides (1 and 2), together with nine known triterpene glycosides (3-11), were isolated from the seeds of Dolichos lablab (Leguminosae). The structures of the new compounds were determined by spectroscopic analysis, including two-dimensional NMR spectroscopy, and chromatographic analysis of the hydrolyzed products. The isolated compounds did not show cytotoxicity against HL-60 human leukemia cells and HepG2 human hepatoma cells at sample concentrations of 20 µM.


Assuntos
Dolichos/química , Glicosídeos/química , Triterpenos/química , Sobrevivência Celular/efeitos dos fármacos , Dolichos/metabolismo , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Células HL-60 , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Sementes/química , Sementes/metabolismo , Extração em Fase Sólida , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
15.
J Sci Food Agric ; 99(13): 5881-5889, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31206698

RESUMO

BACKGROUND: The suppression of α-glucosidase activity to retard glucose absorption is an important therapy for type-2 diabetes. Corosolic acid (CRA) is a potential antidiabetic component in many plant-based foods and herbs. In this study, the interplay mechanism between α-glucosidase and corosolic acid was investigated by several methods, including three-dimensional fluorescence spectra, circular dichroism spectra, and molecular simulation. RESULTS: Corosolic acid significantly inhibited α-glucosidase reversibly in an uncompetitive manner and its IC50 value was 1.35 × 10-5 mol L-1 . A combination of CRA with myricetin exerted a weak synergy against α-glucosidase. The intrinsic fluorescence of α-glucosidase was quenched via a static quenching course and the binding constant was 3.47 × 103 L mol-1 at 298 K. The binding of CRA to α-glucosidase was mainly driven by hydrophobic forces and resulted in a partial extension of the protein polypeptide chain with a loss of α-helix content. The molecular simulation illustrated that CRA bound to the entrance part of the active center of α-glucosidase and interacted with the amino acid residues Ser157, Arg442, Phe303, Arg315, Tyr158, and Gln353, which could hinder the release of substrate and catalytic reaction product, eventually suppressing the catalytic activity of α-glucosidase. CONCLUSIONS: These results may suggest new insights into corosolic acid from food sources as a potential α-glucosidase inhibitor that could better control diabetes. © 2019 Society of Chemical Industry.


Assuntos
Inibidores Enzimáticos/química , Triterpenos/química , alfa-Glucosidases/química , Motivos de Aminoácidos , Sítios de Ligação , Dicroísmo Circular , Humanos , Hipoglicemiantes/química , Simulação de Acoplamento Molecular
16.
Am J Chin Med ; 47(4): 769-785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091976

RESUMO

Tripterygium wilfordii Hook F. (TWHF), a traditional Chinese medicine, has been widely used to treat autoimmune and inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus and dermatomyositis in China. Recently, studies have demonstrated that the bioactive components of TWHF have effective therapeutic potential for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Multiple Sclerosis. In this paper, we summarize the research progress of triptolide and celastrol (the two major TWHF components) as well as their analogues in the treatment of neurodegenerative diseases. In addition, we review and discuss the molecular mechanisms and structure features of those two bioactive TWHF components, highlighting their therapeutic promise in neurodegenerative diseases.


Assuntos
Diterpenos/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Fenantrenos/uso terapêutico , Fitoterapia , Tripterygium/química , Triterpenos/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Animais , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Compostos de Epóxi/química , Compostos de Epóxi/isolamento & purificação , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Conformação Molecular , Fármacos Neuroprotetores , Doença de Parkinson/tratamento farmacológico , Fenantrenos/química , Fenantrenos/isolamento & purificação , Fenantrenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
17.
Chem Biodivers ; 16(7): e1900202, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115136

RESUMO

Asprellosides A-K, nine new ursane-type triterpenoid glycosides (1-9), and two new oleanane-type triterpenoid glycosides (10 and 11), including six rare sulfated triterpenoid glycosides, were isolated from the roots of Ilex asprella. Their structures were determined on the basis of comprehensive spectroscopic analysis and chemical methods. Among these compounds, asprelloside B (2) and asprelloside C (3) are the first examples of triterpenoid glycosides bearing a rare 3,4-O-disulfo-xylopyranosyl residue. All the saponins isolated showed no significant effects against respiratory syncytial virus (RSV) and lipopolysaccharide-induced nitric oxide production in Raw264.7 macrophages.


Assuntos
Antivirais/farmacologia , Glicosídeos/farmacologia , Ilex/química , Óxido Nítrico/antagonistas & inibidores , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Antivirais/química , Antivirais/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Conformação Molecular , Óxido Nítrico/biossíntese , Raízes de Plantas/química , Células RAW 264.7 , Triterpenos/química , Triterpenos/isolamento & purificação
18.
Fitoterapia ; 136: 104181, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31145984

RESUMO

The plants of Lycopodiaceae family, distributed across China, India and also Southeast Asia, have been used as folk medicines. The phytochemical constitutent studies of this family was widely reported. Serratene trierpenoids is one of phytochemical constitutent type, which have been mainly isolated from this plant family. To date, more than 100 serratene-type triterpenoids have been reported and several of them have been shown promising biological activities, especially cytotoxicity and chemopreventive activity. This review covers the structural classification, biological activities and hypotheses about biosynthetic pathways of serratene-type triterpenes.


Assuntos
Lycopodiaceae/química , Triterpenos/farmacologia , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Triterpenos/química
19.
Molecules ; 24(9)2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31060200

RESUMO

Leea asiatica (L.) Ridsdale (Leeaceae) is found in tropical and subtropical countries and has historically been used as a traditional medicine in local healthcare systems. Although L. asiatica extracts have been found to possess anthelmintic and antioxidant-related nephroprotective and hepatoprotective effects, little attention has been paid toward the investigation of phytochemical constituents of this plant. In the current study, phytochemical analysis of isolates from L. asiatica led to the identification of 24 compounds, including a novel phenolic glucoside, seven triterpenoids, eight flavonoids, two phenolic glycosides, four diglycosidic compounds, and two miscellaneous compounds. The phytochemical structures of the isolates from L. asiatica were elucidated using spectroscopic analyses including 1D- and 2D-NMR and ESI-Q-TOF-MS. The presence of triterpenoids and flavonoids supports the evidence for anthelmintic and antioxidative effects of L. asiatica.


Assuntos
Compostos Fitoquímicos/análise , Vitaceae/química , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Medicina Tradicional , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
20.
Molecules ; 24(9)2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31058835

RESUMO

In several European countries, especially in Sweden, the seeds of the species Astragalus boeticus L. were widely used as coffee substitutes during the 19th century. Nonetheless, data regarding the phytochemistry and the pharmacological properties of this species are currently extremely limited. Conversely, other species belonging to the Astragalus genus have already been extensively investigated, as they were used for millennia for treating various diseases, including cancer. The current work was addressed to characterize cycloartane glycosides from A. boeticus, and to evaluate their cytotoxicity towards human colorectal cancer (CRC) cell lines. The isolation of the metabolites was performed by using different chromatographic techniques, while their chemical structures were elucidated by nuclear magnetic resonance (NMR) (1D and 2D techniques) and electrospray-ionization quadrupole time-of-flight (ESI-QTOF) mass spectrometry. The cytotoxic assessment was performed in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in Caco-2, HT-29 and HCT-116 CRC cells. As a result, the targeted phytochemical study of A. boeticus enabled the isolation of three new cycloartane glycosides, 6-O-acetyl-3-O-(4-O-malonyl)-ß-d-xylopyranosylcycloastragenol (1), 3-O-(4-O-malonyl)-ß-d-xylopyranosylcycloastragenol (2), 6-O-acetyl-25-O-ß-d-glucopyranosyl-3-O-ß-d-xylopyranosylcycloastragenol (3) along with two known compounds, 6-O-acetyl-3-O-ß-d-xylopyranosylcycloastragenol (4) and 3-O-ß-d-xylopyranosylcycloastragenol (5). Importantly, this work demonstrated that the acetylated cycloartane glycosides 1 and 4 might preferentially inhibit cell growth in the CRC cell model resistant to epidermal growth factor receptor (EGFR) inhibitors.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Astrágalo (Planta)/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glicosídeos/farmacologia , Triterpenos/química , Acilação , Antineoplásicos Fitogênicos/química , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glicosídeos/química , Células HCT116 , Células HT29 , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray , Suécia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA