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1.
Ann Bot ; 131(4): 635-654, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-36681900

RESUMO

BACKGROUND AND AIMS: Among the numerous pantropical species of the yam genus, Dioscorea, only a small group occurs in the Mediterranean basin, including two narrow Pyrenean endemics (Borderea clade) and two Mediterranean-wide species (D. communis and D. orientalis, Tamus clade). However, several currently unrecognized species and infraspecific taxa have been described in the Tamus clade due to significant morphological variation associated with D. communis. Our overarching aim was to investigate taxon delimitation in the Tamus clade using an integrative approach combining phylogenomic, spatial and morphological data. METHODS: We analysed 76 herbarium samples using Hyb-Seq genomic capture to sequence 260 low-copy nuclear genes and plastomes, together with morphometric and environmental modelling approaches. KEY RESULTS: Phylogenomic reconstructions confirmed that the two previously accepted species of the Tamus clade, D. communis and D. orientalis, are monophyletic and form sister clades. Three subclades showing distinctive geographic patterns were identified within D. communis. These subclades were also identifiable from morphometric and climatic data, and introgression patterns were inferred between subclades in the eastern part of the distribution of D. communis. CONCLUSIONS: We propose a taxonomy that maintains D. orientalis, endemic to the eastern Mediterranean region, and splits D. communis sensu lato into three species: D. edulis, endemic to Macaronesia (Canary Islands and Madeira); D. cretica, endemic to the eastern Mediterranean region; and D. communis sensu stricto, widespread across western and central Europe. Introgression inferred between D. communis s.s. and D. cretica is likely to be explained by their relatively recent speciation at the end of the Miocene, disjunct isolation in eastern and western Mediterranean glacial refugia and a subsequent westward recolonization of D. communis s.s. Our study shows that the use of integrated genomic, spatial and morphological approaches allows a more robust definition of species boundaries and the identification of species that previous systematic studies failed to uncover.


Assuntos
Dioscorea , Dioscoreaceae , Tamus , Dioscorea/genética , Filogenia , Genômica , Filogeografia
2.
Molecules ; 27(23)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36500291

RESUMO

Eleven highly oxidized withanolides, chantriolides F-P (1-11), together with six known analogues (12-17), were isolated from the rhizomes of Tacca chantrieri. Their structures were established on the basis of comprehensive spectroscopic data analysis and comparison with published NMR data, and their absolute configurations were further confirmed by experimental ECD data and single crystal X-ray diffraction analysis. The structures of compounds 5-8 contained a chlorine atom substituted at C-3. Compounds 1 and 12 are a pair of epimers isomerized at C-24 and C-25, while compounds 9 and 16 are isomerized at C-1, C-7, C-24, and C-25. Next, the hepatoprotective effect of all the isolates was evaluated on tert-butyl hydroperoxide (t-BHP)-injured AML12 hepatocytes. Compounds 5-11 and 16 significantly enhanced cell viability. Compound 8 decreased reactive oxygen species accumulation and increased glutathione level in t-BHP injured AML12 hepatocytes through promoting nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2).


Assuntos
Dioscoreaceae , Vitanolídeos , Vitanolídeos/farmacologia , Dioscoreaceae/química , Rizoma/química , terc-Butil Hidroperóxido/farmacologia , Espécies Reativas de Oxigênio/análise , Estresse Oxidativo
3.
Molecules ; 27(23)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36500698

RESUMO

Tacca leontopetaloides (T. leontopetaloides) contain a number of active compounds such as flavonoids, tannins, phenolics, steroids, and alkaloids. The active compounds from plants have been shown to reduce the risk of cardiovascular disease by lowering cholesterol levels by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-coenzym A (HMG-CoA) reductase activity. This study aims to investigate the potential active compounds in the ethanolic extract of Tacca tubers (T. leontopetaloides) from the Banyak Islands, Aceh Singkil Regency, Aceh Province both in vitro and in silico. Tacca tubers contain secondary metabolites including flavonoids, phenolics, tannins, steroids and saponins, according to phytochemical screening. In vitro investigation of ethanolic extract of Tacca tuber revealed inhibitory activity of HMG Co-A reductase with an IC50 value of 4.92 ppm. Based on the in silico study, active compound from the extract, namely Stigmasterol with the highest binding affinities with HMG Co-A reductase (-7.2 kcal/mol). As a comparison, the inhibition of HMG Co-A reductase activity by simvastatin with an IC50 4.62 ppm and binding affinity -8.0 Kcal/mol. Our findings suggest that the ethanolic extract of Tacca tuber (T. leontopetaloides) from Banyak Islands, Aceh Province has the potential to inhibit the activity of HMG Co-A reductase.


Assuntos
Dioscoreaceae , Inibidores de Hidroximetilglutaril-CoA Redutases , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Sinvastatina , Esteroides , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Oxirredutases
4.
J Econ Entomol ; 115(6): 1921-1929, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36287632

RESUMO

The acaricidal activities of 86 plant extracts were investigated under laboratory conditions. The ethanol extract of Dioscorea japonica Thunb. root showed the strongest acaricidal activity, with 89.3% mortality against two-spotted spider mite, Tetranychus urticae Koch adults at a 2 mg/ml concentration. Bioassay-guided isolation of D. japonica root extract using silica gel open column chromatography, gas chromatography (GC), and gas chromatography-mass spectrometry (GC-MS) identified palmitic acid as the primary active compound. The acaricidal activities of palmitic acid against T. urticae were 91.2% and 69.7% at concentrations of 1 and 0.5 mg/ml, respectively. Among nine saturated fatty acids with carbon chains ranging from C8 to C26, the most vigorous acaricidal activity was observed with octanoic acid, followed by palmitic acid, and decanoic acid at a 1 mg/ml concentration. The acaricidal activity of the other fatty acids was less than 40% mortality at a 1 mg/ml concentration. These results indicate that a suitable carbon length is essential for fatty acids to exhibit acaricidal activity. The acaricidal efficacy of Eungjinssag (EJSG), an organic agricultural material authorized for the management of mites in the Republic of Korea, was compared to D. japonica root extract. At concentrations above 1 mg/ml, the acaricidal activity of D. japonica root extract was stronger than that of EJSG. The results of this study show that D. japonica root extract and palmitic acid are promising candidates as new environmentally-friendly control agents against two-spotted spider mite, which is one of the most severely damaging agricultural arthropod pests.


Assuntos
Acaricidas , Dioscorea , Dioscoreaceae , Tetranychidae , Animais , Acaricidas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ácidos Graxos , Carbono , Ácidos Palmíticos
5.
J Nat Prod ; 84(8): 2265-2271, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34355562

RESUMO

Seven highly oxidized steroids, taccachatrones A-G (1-7), together with four known taccalonolides (8-11), were characterized from the rhizomes of Tacca chantrieri. The structures of 1-7 were established on the basis of spectroscopic data analysis, while the absolute configurations were determined by single-crystal X-ray diffraction. Compounds 1-4 may be derived from taccalonolide derivatives by the degradation of three carbon atoms. Compounds 7, 8, 10, and 11 exhibited cytotoxicity to human cancer cell lines, indicating that the presence of a lactone moiety, as well as a double bond between C-22 and C-23, might play key roles in mediating their cytotoxicity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Dioscoreaceae/química , Esteroides/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Rizoma/química , Esteroides/isolamento & purificação
6.
Prog Chem Org Nat Prod ; 112: 183-206, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33306174

RESUMO

Microtubule stabilizers are a mainstay in the treatment of many solid cancers and continue to find utility in combination therapy with molecularly targeted anticancer agents and immunotherapeutics. However, innate and acquired resistance to microtubule stabilizers can limit their clinical efficacy. The taccalonolides are a unique class of microtubule stabilizers isolated from plants of Tacca that circumvent clinically relevant mechanisms of drug resistance. Although initial reports suggested that the microtubule-stabilizing activity of the taccalonolides was independent of direct tubulin binding, additional studies have identified that potent C-22, C-23 epoxidized taccalonolides covalently bind the Aspartate 226 residue of ß-tubulin and that this interaction is critical for their microtubule-stabilizing activity. The taccalonolides have distinct properties as compared to other microtubule stabilizers with regard to their biochemical effects on tubulin structure and dynamics that promote distinct cellular phenotypes. Some taccalonolides have demonstrated in vivo antitumor efficacy in drug-resistant tumor models with exquisite potency and long-lasting antitumor efficacy as a result of their irreversible target engagement. The recent identification of a site on the taccalonolide scaffold that is amenable to modification has provided evidence of the specificity of the taccalonolide-tubulin interaction. This also affords an opportunity to further optimize the targeted delivery of the taccalonolides to further improve their anticancer efficacy and potential for clinical development.


Assuntos
Dioscoreaceae , Microtúbulos , Esteroides , Dioscoreaceae/química , Dioscoreaceae/metabolismo , Microtúbulos/efeitos dos fármacos , Esteroides/química , Esteroides/farmacologia , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo
7.
J Nat Prod ; 83(12): 3681-3688, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33253561

RESUMO

Three new dimeric diarylheptanoids, taccachanfurans A-C (1-3), a new monomeric diarylheptanoid, taccachannoid A (4), and four known diarylheptanoids (5-8) were isolated from the EtOH extract of the rhizomes of Tacca chantrieri. Their structures were established on the basis of comprehensive spectroscopic data analysis. The absolute configuration of taccachanfuran A (1) was confirmed by single-crystal X-ray diffraction. All the diarylheptanoid dimers contain a ditetrahydrofuran moiety, which has not been described previously for diarylheptanoid compounds. A plausible biosynthetic pathway for the diarylheptanoid dimers is proposed. Compounds 2-4 showed significant neuroprotective activity against Aß25-35-induced damage in SH-SY5Y cells at the concentrations of 10 and 1 µM. Compounds 3, 4, 6, 7, and 8 showed anti-inflammatory activity in LPS-stimulated murine microglial BV-2 cells at the concentrations of 10 and 1 µM.


Assuntos
Anti-Inflamatórios/farmacologia , Diarileptanoides/química , Dioscoreaceae/química , Fármacos Neuroprotetores/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Análise Espectral/métodos
8.
Biomed Chromatogr ; 34(9): e4867, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32330320

RESUMO

Rhizoma Dioscoreae Makino (RDM) is effective in treating gouty arthritis (GA) and hyperuricacidemia, especially in promoting uric acid excretion and reducing the inflammatory reaction. Bioactive constituents in RDM are mainly steroidal saponins such as dioscin, trillin, protodioscin and protogracillin. However, the mechanism of its anti-GA action is still unclear, owing to the complex pathological and physiological characteristics of GA, and integration of RDM with multiple components, multiple targets and multiple pathways. Herein, a GA rat model was induced with monosodium urate (MSU), and RDM reduced inflammation of rat synovium tissue. Through metabolomics analysis, 35 potential biomarkers with significant changes involved in the pathogenesis of GA induced by MSU were identified, and perturbations were restored after RDM treatment. The most correlated pathways involved in d-galactose, d-mannose, d-glucose, myoinositol, Phosphatidylcholine (PC) (16:0/16:0), LysoPC (15:0), phosphatidic acid (PA) [18:1(9Z)/18:1(11Z)] and glutathione induced by MSU were galactose metabolism, inositol phosphate metabolism, glycerophospholipid metabolism and glutathione metabolism, and the derivations of all those biomarkers could be regulated by RDM treatment. RDM has a therapeutic effect on GA by intervening in changes in endogenous metabolisms and the related metabolic pathways.


Assuntos
Artrite Gotosa/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Saponinas/farmacologia , Animais , Cromatografia Líquida de Alta Pressão/métodos , Dioscoreaceae , Modelos Animais de Doenças , Ensaios de Triagem em Larga Escala , Masculino , Espectrometria de Massas/métodos , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
9.
Med Sci Monit ; 25: 9028-9041, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31776323

RESUMO

BACKGROUND This study identified microRNAs (miRNAs) and mRNAs associated with Compound Longmaining (CLMN) treatment of acute myocardial infarction (AMI). Our results provide a theoretical framework to guide AMI treatment and improve myocardial injury. MATERIAL AND METHODS The myocardial tissues of the sham operation group (S), the model group (M), and the CLMN treatment group (T) were obtained. The mRNA and miRNA expression profiles were identified using RNA-sequencing analysis. The sequencing results were verified by quantitative real-time PCR (qRT-PCR). Bioinformatics was used to predict the function of differentially expressed genes (DEGs) and related signal transduction pathways. The target genes of miRNAs were predicted by software analysis, and the relationship between miRNA and mRNA was studied by network analysis. RESULTS RNA-sequencing revealed 22 differentially expressed miRNAs (DEMs) and 76 DEGs in myocardial tissue. Six DEMs and 9 DEGs were randomly selected for qRT-PCR validation, and corroborating results were obtained. The results of Gene ontology (GO) showed that DEGs participated in different biological processes. Through the combined analysis of miRNAs and mRNAs expression, it was confirmed that a single miRNA is involved in the regulation of multiple genes, and also multiple miRNAs can target one gene. CONCLUSIONS The analysis based on the miRNA-mRNA network can not only help to elucidate the potential molecular mechanism of CLMN treatment of AMI, but can also help in identifying novel therapeutic targets.


Assuntos
Medicina Tradicional Chinesa/métodos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Animais , China , Dioscoreaceae , Medicamentos de Ervas Chinesas/farmacologia , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Miocárdio/metabolismo , Própole , Pueraria , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Transcriptoma/genética
10.
Microsc Res Tech ; 82(12): 2061-2071, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31576622

RESUMO

In this paper, we studied pollen morphologies of seven species in genus Aletris in detail by light microscopy and scanning electron microscopy. Of these, six species were reported for the first time. The palynological characteristics do not support the infrageneric classification into two clades. The results indicated that pollen grains of Aletris are small or medium with the P/E ratio of 0.36-0.59. They are elliptic or long-elliptic in the polar view with blunt, round or acute ends and bilateral symmetric with a monosulcate, narrow or wide, deep colpus that has length extending to the ends of pollen grains, obvious or absent colpus membranes. The pollen ornamentation is gemmate, perforated, or reticulate. The sexine is slightly or quite thicker than the nexine.


Assuntos
Dioscoreaceae/classificação , Dioscoreaceae/ultraestrutura , Pólen/ultraestrutura , Microscopia Eletrônica de Varredura
11.
Chin J Nat Med ; 16(1): 29-40, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29425588

RESUMO

The underground cane of Schizocapsa plantaginea (Hance) has long been used by Chinese ethnic minority as a constituent of anti-cancer formulae. Saponins are abundant secondary metabolic products located in the underground cane of this plant. The potential therapeutic effects of total saponins isolated from Schizocapsa plantaginea (Hance) (SSPH) on human hepatocellular carcinoma (HCC) were tested in vitro in human liver cancer cell lines, SMMC-7721 and Bel-7404. Apoptosis and cell cycle arrest were determined using flow cytometry, caspase activation was determined by ELISA, and PARP, cleaved PARP, mitogen-activated protein kinase (MAPK) expression and phosphorylation were measured using Western blotting analysis. In vivo anti-HCC effects of SSPH were verified in nude mouse xenograft model. SSPH exerted markedly inhibitory effect on HCC cell proliferation in time- and concentration-dependent manner. Moreover, SSPH significantly induced apoptosis through caspase-dependent signaling and arrested cell cycle at G2/M phase. These anti-proliferation effects of SSPH were associated with up-regulated phosphorylation of extracellular signal-regulated kinase-1/2 (Erk1/2) and c-jun-NH2-kinase-1/2 (JNK1/2) and reduced phosphorylation of p38MAPK. Furthermore, inhibitors of ERK, UO126, and JNK, SP600125 inhibited the anti-proliferation effects by SSPH, suggesting that Erk and JNK were the effector molecules in SSPH induced anti-proliferative action. During in vivo experiments, SSPH was found to inhibit xenograft tumor growth in nude mice, with a similar mechanism in vitro. Our study confirmed that SSPH exerted antagonistic effects on human liver cancer cells both in vitro and in vivo. Molecular mechanisms underlying SSPH action might be closely associated with MAPK signaling pathways. These results indicated that SSPH has potential therapeutic effects on HCC.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Dioscoreaceae/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Saponinas/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/toxicidade , Caspases/genética , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Xenoenxertos/efeitos dos fármacos , Xenoenxertos/crescimento & desenvolvimento , Humanos , Concentração Inibidora 50 , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Fosforilação/efeitos dos fármacos , Tubérculos/química , Poli(ADP-Ribose) Polimerase-1/metabolismo , Saponinas/isolamento & purificação , Saponinas/toxicidade
12.
J Nat Prod ; 81(3): 579-593, 2018 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-29360362

RESUMO

The taccalonolides are a unique class of microtubule stabilizers isolated from Tacca spp. that have efficacy against drug-resistant tumors. Our previous studies have demonstrated that a C-15 acetoxy taccalonolide, AF, has superior in vivo antitumor efficacy compared to AJ, which bears a C-15 hydroxy group. With the goal of further improving the in vivo efficacy of this class of compounds, we semisynthesized and tested the biological activities of 28 new taccalonolides with monosubstitutions at C-7 or C-15 or disubstitutions at C-7 and C-25, covering a comprehensive range of substituents from formic acid to anthraquinone-2-carbonyl chloride. The resulting taccalonolide analogues with diverse C-7/C-15/C-25 modifications exhibited IC50 values from 2.4 nM to >20 µM, allowing for extensive in vitro structure-activity evaluations. This semisynthetic strategy was unable to provide a taccalonolide with improved therapeutic window due to hydrolysis of substituents at C-7 or C-15 regardless of size or steric bulk. However, two of the most potent new taccalonolides, bearing isovalerate modifications at C-7 or C-15, demonstrated potent and highly persistent antitumor activity in a drug-resistant xenograft model when administered intratumorally. This study demonstrates that targeted delivery of the taccalonolides to the tumor could be an effective, long-lasting approach to treat drug-resistant tumors.


Assuntos
Dioscoreaceae/química , Microtúbulos/efeitos dos fármacos , Esteroides/química , Esteroides/farmacologia , Animais , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Nus , Microtúbulos/química , Esteroides/síntese química
13.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-773641

RESUMO

The underground cane of Schizocapsa plantaginea (Hance) has long been used by Chinese ethnic minority as a constituent of anti-cancer formulae. Saponins are abundant secondary metabolic products located in the underground cane of this plant. The potential therapeutic effects of total saponins isolated from Schizocapsa plantaginea (Hance) (SSPH) on human hepatocellular carcinoma (HCC) were tested in vitro in human liver cancer cell lines, SMMC-7721 and Bel-7404. Apoptosis and cell cycle arrest were determined using flow cytometry, caspase activation was determined by ELISA, and PARP, cleaved PARP, mitogen-activated protein kinase (MAPK) expression and phosphorylation were measured using Western blotting analysis. In vivo anti-HCC effects of SSPH were verified in nude mouse xenograft model. SSPH exerted markedly inhibitory effect on HCC cell proliferation in time- and concentration-dependent manner. Moreover, SSPH significantly induced apoptosis through caspase-dependent signaling and arrested cell cycle at G/M phase. These anti-proliferation effects of SSPH were associated with up-regulated phosphorylation of extracellular signal-regulated kinase-1/2 (Erk1/2) and c-jun-NH2-kinase-1/2 (JNK1/2) and reduced phosphorylation of p38MAPK. Furthermore, inhibitors of ERK, UO126, and JNK, SP600125 inhibited the anti-proliferation effects by SSPH, suggesting that Erk and JNK were the effector molecules in SSPH induced anti-proliferative action. During in vivo experiments, SSPH was found to inhibit xenograft tumor growth in nude mice, with a similar mechanism in vitro. Our study confirmed that SSPH exerted antagonistic effects on human liver cancer cells both in vitro and in vivo. Molecular mechanisms underlying SSPH action might be closely associated with MAPK signaling pathways. These results indicated that SSPH has potential therapeutic effects on HCC.


Assuntos
Animais , Humanos , Camundongos , Antineoplásicos , Farmacologia , Toxicidade , Apoptose , Caspases , Genética , Metabolismo , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Dioscoreaceae , Química , Xenoenxertos , Concentração Inibidora 50 , Neoplasias Hepáticas , Tratamento Farmacológico , Metabolismo , Patologia , Sistema de Sinalização das MAP Quinases , Camundongos Nus , Fosforilação , Tubérculos , Química , Poli(ADP-Ribose) Polimerase-1 , Metabolismo , Saponinas , Farmacologia , Toxicidade
14.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-812431

RESUMO

The underground cane of Schizocapsa plantaginea (Hance) has long been used by Chinese ethnic minority as a constituent of anti-cancer formulae. Saponins are abundant secondary metabolic products located in the underground cane of this plant. The potential therapeutic effects of total saponins isolated from Schizocapsa plantaginea (Hance) (SSPH) on human hepatocellular carcinoma (HCC) were tested in vitro in human liver cancer cell lines, SMMC-7721 and Bel-7404. Apoptosis and cell cycle arrest were determined using flow cytometry, caspase activation was determined by ELISA, and PARP, cleaved PARP, mitogen-activated protein kinase (MAPK) expression and phosphorylation were measured using Western blotting analysis. In vivo anti-HCC effects of SSPH were verified in nude mouse xenograft model. SSPH exerted markedly inhibitory effect on HCC cell proliferation in time- and concentration-dependent manner. Moreover, SSPH significantly induced apoptosis through caspase-dependent signaling and arrested cell cycle at G/M phase. These anti-proliferation effects of SSPH were associated with up-regulated phosphorylation of extracellular signal-regulated kinase-1/2 (Erk1/2) and c-jun-NH2-kinase-1/2 (JNK1/2) and reduced phosphorylation of p38MAPK. Furthermore, inhibitors of ERK, UO126, and JNK, SP600125 inhibited the anti-proliferation effects by SSPH, suggesting that Erk and JNK were the effector molecules in SSPH induced anti-proliferative action. During in vivo experiments, SSPH was found to inhibit xenograft tumor growth in nude mice, with a similar mechanism in vitro. Our study confirmed that SSPH exerted antagonistic effects on human liver cancer cells both in vitro and in vivo. Molecular mechanisms underlying SSPH action might be closely associated with MAPK signaling pathways. These results indicated that SSPH has potential therapeutic effects on HCC.


Assuntos
Animais , Humanos , Camundongos , Antineoplásicos , Farmacologia , Toxicidade , Apoptose , Caspases , Genética , Metabolismo , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Dioscoreaceae , Química , Xenoenxertos , Concentração Inibidora 50 , Neoplasias Hepáticas , Tratamento Farmacológico , Metabolismo , Patologia , Sistema de Sinalização das MAP Quinases , Camundongos Nus , Fosforilação , Tubérculos , Química , Poli(ADP-Ribose) Polimerase-1 , Metabolismo , Saponinas , Farmacologia , Toxicidade
15.
J Int Med Res ; 44(6): 1395-1402, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27856932

RESUMO

Objective Taccaoside, a steroidal saponin, has been shown to be cytotoxic, although the mechanism of cytotoxicity remains unclear. This study examined the effect of taccaoside on the human hepatocellular carcinoma (HCC) cell lines SMMC-7721 and Bel-7404. Methods The antiproliferative effect of taccaoside were measured using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Cells were stained with Hoechst 33258 to observe morphology. Cell cycle and apoptosis were analysed by flow cytometry. Caspase activation was detected using specific assays, and PARP, Bax and Bcl-2 expression were analysed using western blotting. Results Taccaoside showed antiproliferative effect on HCC cell lines growth in a concentration- and time-dependent manner. Taccaoside arrested cell cycle in the G2/M phase and induced caspase-dependent apoptosis. Western blotting indicated that taccaoside upregulated Bax expression and downregulated Bcl-2 expression. PARP cleavage was observed following taccaoside treatment. Conclusions This study showed that taccaoside may inhibit HCC cell proliferation by inducing apoptosis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Dioscoreaceae/química , Regulação Neoplásica da Expressão Gênica , Hepatócitos/efeitos dos fármacos , Saponinas/farmacologia , Esteroides/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/genética , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Extratos Vegetais/química , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteólise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Saponinas/isolamento & purificação , Transdução de Sinais , Esteroides/isolamento & purificação , Proteína X Associada a bcl-2/agonistas , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
16.
BMC Evol Biol ; 16(1): 238, 2016 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-27821045

RESUMO

BACKGROUND: Dioscorea is a widely distributed and highly diversified genus in tropical regions where it is represented by ten main clades, one of which diversified exclusively in Africa. In southern Africa it is characterised by a distinct group of species with a pachycaul or "elephant's foot" structure that is partially to fully exposed above the substrate. In contrast to African representatives of the genus from other clades, occurring mainly in forest or woodland, the pachycaul taxa and their southern African relatives occur in diverse habitats ranging from woodland to open vegetation. Here we investigate patterns of diversification in the African clade, time of transition from forest to more open habitat, and morphological traits associated with each habitat and evaluate if such transitions have led to modification of reproductive organs and mode of dispersal. RESULTS: The Africa clade originated in the Oligocene and comprises four subclades. The Dioscorea buchananii subclade (southeastern tropical Africa and South Africa) is sister to the East African subclade, which is respectively sister to the recently evolved sister South African (e. g., Cape and Pachycaul) subclades. The Cape and Pachycaul subclades diversified in the east of the Cape Peninsula in the mid Miocene, in an area with complex geomorphology and climate, where the fynbos, thicket, succulent karoo and forest biomes meet. CONCLUSIONS: Diversification out of forest is associated with major shifts in morphology of the perennial tuber (specifically an increase in size and orientation which presumably led them to become pachycaul) and rotation of stem (from twining to non-twining). The iconic elephant's foot morphology, observed in grasslands and thicket biomes, where its corky bark may offer protection against fire and herbivory, evolved since mid Miocene. A shift in pollination trait is observed within the forest, but entry into open habitat does not show association with reproductive morphology, except in the seed wing, which has switched from winged all round the seed margin to just at the base or at the apex of it, or has been even replaced by an elaiosome.


Assuntos
Dioscorea/anatomia & histologia , Dioscoreaceae/anatomia & histologia , Ecossistema , Folhas de Planta/anatomia & histologia , África , Animais , Clima , Dioscorea/classificação , Dioscorea/fisiologia , Dioscoreaceae/classificação , Dioscoreaceae/fisiologia , Filogenia
17.
Am J Bot ; 103(6): 1129-37, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27335389

RESUMO

PREMISE OF THE STUDY: Heterotrophic angiosperms tend to have reduced plastome sizes relative to those of their autotrophic relatives because genes that code for proteins involved in photosynthesis are lost. However, some plastid-encoded proteins may have vital nonphotosynthetic functions, and the plastome therefore may be retained after the loss of photosynthesis. METHODS: We sequenced the plastome of the mycoheterotrophic species Thismia tentaculata and a representative of its sister genus, Tacca chantrieri, using next-generation technology, and we compared sequences and structures of genes and genomes of these species. KEY RESULTS: The plastome of Tacca chantrieri is similar to those of other autotrophic taxa of Dioscoreaceae, except in a few local rearrangements and one gene loss. The plastome of Thismia tentaculata is ca. 16 kbp long with a quadripartite structure and is among the smallest known plastomes. Synteny is minimal between the plastomes of Tacca chantrieri and Thismia tentaculata. The latter includes only 12 candidate genes, with all except accD involved in protein synthesis. Of the 12 genes, trnE, trnfM, and accD are frequently among the few that remain in depauperate plastomes. CONCLUSIONS: The plastome of Thismia tentaculata, like those of most other heterotrophic plants, includes a small number of genes previously suggested to be essential to plastome survival.


Assuntos
Processos Autotróficos/genética , Dioscoreaceae/genética , Tamanho do Genoma , Genomas de Plastídeos , Processos Heterotróficos/genética , Magnoliopsida/genética , Flores/anatomia & histologia , Genes de Plantas , Estudos de Associação Genética , Hong Kong , Nucleotídeos/genética , Transcrição Gênica
18.
Phytochem Anal ; 27(3-4): 217-21, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27313159

RESUMO

INTRODUCTION: Several taccalonolides with various bioactivities have been isolated from Tacca species but no studies to isolate taccalonolides with anti-trypanosomal activity from Tacca leontopetaloides have been reported. OBJECTIVES: To analyse extracts of the roots of Tacca leontopetaloides, purify the extracts by column chromatography and identify isolated compounds by spectroscopic methods. The compounds and fractions will be tested for antitrypanosomal activity in vitro against Trypanosoma brucei brucei. MATERIAL AND METHODS: Dried roots or tubers of Tacca leontopetaloides, chromatographic separation and spectroscopic identification. RESULTS: A novel taccalonolide A propanoate and some known taccalonolides were isolated and their structures were determined by NMR and mass spectrometry CONCLUSION: Several taccalonolides were isolated from Tacca leontopetaloides and were found to have in vitro antitrypanosomal activity against Trypanosoma brucei brucei and EC50 values for the isolated compounds were from 0.79 µg/mL. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Dioscoreaceae/química , Extratos Vegetais/farmacologia , Esteroides/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Espectrometria de Massas , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Tubérculos/química , Propionatos/química , Propionatos/isolamento & purificação , Propionatos/farmacologia , Esteroides/química , Esteroides/isolamento & purificação , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificação
19.
Bioorg Med Chem Lett ; 26(15): 3780-4, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27287369

RESUMO

Using various chromatographic methods, five new steroidal saponins named taccavietnamosides A-E (1-5) and three known, (24S,25R)-spirost-5-en-3ß,24-diol 3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→3)]-ß-d-glucopyranoside (6), (24S,25R)-spirost-5-en-3ß,24-diol 3-O-α-l-rhamnopyranosyl-(1→2)-[ß-d-glucopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→3)]-ß-d-glucopyranoside (7), and chantrieroside A (8) were isolated from the rhizomes of Tacca vietnamensis Thin et Hoat. Their chemical structures were elucidated by physical and chemical methods. All compounds were evaluated for the inhibitory activities of nitric oxide production in LPS-stimulated RAW 264.7 macrophages and BV2 cells. As the results, compounds 3-5 showed moderate inhibition on NO production in LPS-stimulated BV2 cells and RAW 264.7 macrophages with the IC50 values ranging from 37.0 to 60.7µM.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Dioscoreaceae/química , Óxido Nítrico/antagonistas & inibidores , Saponinas/farmacologia , Espirostanos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Linhagem Celular , Relação Dose-Resposta a Droga , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Células RAW 264.7 , Saponinas/química , Saponinas/isolamento & purificação , Espirostanos/química , Espirostanos/isolamento & purificação , Relação Estrutura-Atividade
20.
Nat Prod Commun ; 11(1): 45-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26996017

RESUMO

Two new steroidal glucosides, chantriolides D and E (1 and 2), along with four known compounds, chantriolide A (3), chantriolide B (4), chantriolide C (5), and (25S)-spirost-5-en-3-ol 3-O-α-L-rhamnopyranosyl-(1-->2)-O-[α-L-rhamnopyranosyl-(1-->3)]-ß-D-glucopyranoside (6) were isolated from the rhizomes of Tacca chantrieri. Their structures were determined by 1D and 2D NMR spectroscopic and HR-ESI-MS data, as well as by comparison with reported data. Compounds 1 and 2 were found to show strong inhibitory NO effect in BV2 cells, with IC50 values of 12.45 and 59.03 µM, respectively.


Assuntos
Dioscoreaceae/química , Glucosídeos/farmacologia , Microglia/efeitos dos fármacos , Óxido Nítrico/biossíntese , Rizoma/química , Linhagem Celular , Glucosídeos/química , Humanos , Microglia/metabolismo , Estrutura Molecular
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