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1.
Chem Biol Interact ; 331: 109246, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877639

RESUMO

Colorectal cancer (CRC) represents one of the commonest malignancies around the world. PP9, a natural steroidal saponin, was firstly isolated from the rhizomes of Paris polyphylla var. latifolia. However, the therapeutic effects of PP9 on CRC and the underlying molecular mechanism remain undefined. Here, we demonstrated that treatment with PP9 time- and dose-dependently inhibited HT-29 and HCT116 cells without significantly inhibiting normal NCM460 cells. Furthermore, our results indicated that PP9 effectively induced G2/M phase arrest by upregulating p21 and suppressing cdc25C, Cyclin B1 and cdc2. Meanwhile, PP9 upregulated cleaved Caspase 3, cleaved Caspase 9 and cleaved PARP and Bax, while downregulating Bcl-2 to stimulate cell apoptosis. Mechanistically, PP9-suppressed PI3K/Akt/GSK3ß signaling, while the PI3K inhibitor LY294002 augmented PP9-mediated apoptosis, G2/M arrest and effects on PI3K/Akt/GSK3ß related proteins. Finally, we showed that PP9 (10 mg/kg) significantly reduced tumor growth in nude mouse CRC xenografts, more potently than 5-Fu (20 mg/kg). Jointly, these data firstly demonstrated that PP9 promotes G2/M arrest and apoptotic death in CRC cells through PI3K/Akt/GSK3ß signaling suppression, suggesting that PP9 could be considered a new and promising candidate for CRC therapy.


Assuntos
Apoptose/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Caspase 3/metabolismo , Linhagem Celular Tumoral , Cromonas/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Liliales/química , Liliales/metabolismo , Masculino , Camundongos , Camundongos Nus , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Saponinas/uso terapêutico , Transplante Heterólogo
2.
Molecules ; 23(3)2018 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-29509694

RESUMO

Four new spirostanol saponins, named pavitnosides A-D (1-4), with six known steroidal saponins 5-10 were isolated from the rhizomes of Paris vietnamensis. Their chemical structures were determined based on extensive spectroscopic studies and chemical methods. The aglycones of pavitnoside B and pavitnoside C were not reported in previous work. The cytotoxicity of all saponins was evaluated against human glioblastoma U87MG and U251 cell lines. The new spirostanol saponin 1 displayed weak anti-proliferative activity against U87MG cell line and the known saponins 8 and 9 exhibited significant cytotoxicity against the two tumor cell lines, with IC50 values of 2.16 to 3.14 µM, but did not affect the growth of primary cultures of human astrocytes.


Assuntos
Citotoxinas/química , Liliales/química , Saponinas/química , Linhagem Celular Tumoral , Células Cultivadas , Citotoxinas/toxicidade , Humanos , Rizoma/química , Saponinas/isolamento & purificação , Saponinas/toxicidade , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/toxicidade
3.
Pediatr Diabetes ; 18(1): 10-16, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28052534

RESUMO

Metformin is a widely prescribed medication that has been used to treat children with type 2 diabetes in the United States for the past 15 years. Metformin now has a variety of clinical applications in pediatrics, and its potential clinical uses continue to expand. In addition to reviewing the current understanding of its mechanisms of action including the newly discovered effects on the gastrointestinal tract, we will also discuss current clinical uses in pediatrics, including in type 1 diabetes. Finally, we examine the existing state of monitoring for metformin efficacy and side effects and discuss prospective future clinical uses.


Assuntos
Liliales/química , Longevidade , Metformina , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Hipoglicemiantes/uso terapêutico , Longevidade/efeitos dos fármacos , Metformina/história , Metformina/isolamento & purificação , Metformina/uso terapêutico
4.
Biomed Chromatogr ; 31(7)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27933644

RESUMO

A rapid method was developed and validated by ultra-performance liquid chromatography-triple quadrupole mass spectroscopy with ultraviolet detection (UPLC-UV-MS) for simultaneous determination of paris saponin I, paris saponin II, paris saponin VI and paris saponin VII. Partial least squares discriminant analysis (PLS-DA) based on UPLC and Fourier transform infrared (FT-IR) spectroscopy was employed to evaluate Paris polyphylla var. yunnanensis (PPY) at different harvesting times. Quantitative determination implied that the various contents of bioactive compounds with different harvesting times may lead to different pharmacological effects; the average content of total saponins for PPY harvested at 8 years was higher than that from other samples. The PLS-DA of FT-IR spectra had a better performance than that of UPLC for discrimination of PPY from different harvesting times.


Assuntos
Cromatografia Líquida/métodos , Liliales/química , Espectrometria de Massas/métodos , Espectrofotometria Ultravioleta/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise dos Mínimos Quadrados , Padrões de Referência
5.
Mitochondrial DNA A DNA Mapp Seq Anal ; 28(2): 159-160, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-26710190

RESUMO

Paris polyphylla var. yunnanensis is a perennial medical plant widely used in traditional Chinese medicine. Here, we report the complete chloroplast genome of P. polyphylla var. yunnanensis. The genome is 157 675 bp in length including a small single-copy region (SSC, 18 319 bp) and a large single-copy region (LSC, 84 108 bp) separated by a pair of inverted repeats (IRs, 27 624 bp). The genome contained 115 genes, including 81 protein-coding genes, 4 ribosomal RNA genes, and 30 tRNA genes. Among these genes, 13 harbored a single intron and 2 contained a couple of introns. The overall G + C content of the cpDNA is 37.4%, while the corresponding values of the LSC, SSC, and IR regions are 35.71%, 31.43%, and 41.87%, respectively. A Maximum-likelihood phylogenetic analysis suggested that genus Trillium, Paris, Fritillaria, and Lilium were strongly supported as monophyletic and the P. polyphylla var. yunnanensis is closely related to Trillium.


Assuntos
Genes de Cloroplastos , Genoma de Cloroplastos , Liliales/genética , Filogenia , Análise de Sequência de DNA , Composição de Bases , DNA de Cloroplastos , Genes de Plantas , Genoma de Planta , Genômica
6.
Mol Carcinog ; 56(5): 1405-1413, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27991692

RESUMO

Lung cancer is the foremost cause of cancer mortality and a growing economic burden worldwide. Rhizoma paridis saponins (RPS) have been reported to exhibit potential anti-tumor effects on many kinds of tumor models. The present study was designed to investigate the mechanism-based chemopreventive nature of RPS against DEN-induced lung carcinogenesis in Kunming mice. As a result, the treatment with RPS reduced the severity of pulmonary histopathology. The mechanism of its antitumor effect involved in (a) reducing oxidative stress injury through up-regulating activities of CAT and SOD; (b) down-regulating the levels of inflammatory factors, like TNF-α, IL6, COX-2, and PGE2; (c) activation of caspase-3 and up-regulating the pro-apoptotic protein Bax; (d) decreasing the expression of PCNA; (e) depressing the expression of cancer stem cells marker CD133; (f) suppressing aberrant expression of cytokeratin 8 and 18; and (g) inhibiting EGFR/ PI3 K/Akt, EGFR/Ras/Erk and NF-κB pathways. Taken together, RPS would be a potent agent inhibiting lung tumor in the future.


Assuntos
Liliales/química , Neoplasias Pulmonares/tratamento farmacológico , Saponinas/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dietilnitrosamina/toxicidade , Receptores ErbB/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Estresse Oxidativo/efeitos dos fármacos , Rizoma/química
7.
Sci Rep ; 6: 34903, 2016 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-27739450

RESUMO

Aconiti Lateralis Radix Praeparata (Fuzi) and Fritillariae Thunbergii bulbus (Beimu) have been widely used clinically to treat cardiopulmonary related diseases in China. However, according to the classic rules of traditional Chinese medicine, Fuzi and Beimu should be prohibited to use as a combination for their incompatibility. Therefore, it is critical to elucidate the paradox on the use of Fuzi and Beimu combination therapy. Monocrotaline-induced pulmonary hypertension rats were treated with either Fuzi, Beimu, or their combination at different stages of PH. We demonstrated that at the early stage of PH, Fuzi and Beimu combination significantly improved lung function and reduced pulmonary histopathology. However, as the disease progressed, when Fuzi and Beimu combination were used at the late stage of PH, right ventricular chamber dilation was histologically apparent and myocardial apoptosis was significantly increased compared with each drug alone. Western-blotting results indicated that the main chemical ingredient of Beimu could down-regulate the protein phosphorylation levels of Akt and PDE4D, whereas the combination of Fuzi and Beimu could up-regulate PKA and CaMKII signaling pathways. Therefore, we concluded that Fuzi and Beimu combination potentially aggravated the heart injury due to the inhibition of PDK1/Akt/PDE4D axis and subsequent synergistic activation of ßAR-Gs-PKA/CaMKII signaling pathway.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Hipertensão Pulmonar/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Combinação de Medicamentos , Medicamentos de Ervas Chinesas , Ecocardiografia , Hemodinâmica , Liliales/química , Masculino , Miocárdio/patologia , Ratos , Ratos Wistar , Transdução de Sinais
8.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(3): 1869-70, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-25319309

RESUMO

Bomarea, a member of the family Alstroemeriaceae, is distributed from Chile to Mexico and includes approximately 120 species. Recent molecular phylogenetic studies have clarified the monophyly of the family within the order Liliales and the sister relationship with the family Colchicaceae. At this time, five plastid genomes of Liliales have been analyzed at the familial level. To examine plastid genome variation at the generic level, we sequenced the plastid genome of Bomarea edulis, which is the most widely distributed species in the genus, and compared it with Alstroemeria aurea. The plastid genome sequence of B. edulis was 154,925 bp in length with a similar structure as A. aurea, excluding the IR-LSC junction. Ycf68 and infA were pseudogenes caused by frameshift mutations, and the ycf15 gene was deleted, similar to A. aurea.


Assuntos
Genomas de Plastídeos , Liliales/genética , Sequenciamento Completo do Genoma , Pareamento de Bases/genética , Sequência de Bases , Mapeamento Cromossômico , Ordem dos Genes , Genes de Cloroplastos
9.
Environ Toxicol ; 31(12): 1935-1943, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26390842

RESUMO

Rhizoma Paridis saponins (RPS), as steroid saponins, are the main components in Paris polyphylla. Curcumin (diferuloylmethane) is the most important component in the spice turmeric. In our previous research, RPS exhibited side effects such as nausea, vomiting, diarrhea, and so forth. Combination with curcumin not only alleviated the toxicity and gastric stimulus induced by RPS, but also improved the quality life of mice bearing tumor cells and enhanced their anticancer effect. This study evaluated subchronic toxicity of 45th dietary of RPS and curcumin on histopathology, biochemistry, and antioxidant index. As a result, RPS-treatment caused a slight liver injury (the elevation of serum AST, alkaline phosphatase (AKP), alanine transaminase (ALT), and gamma glutamyl transpeptidase (γ-GT), histopathological changes in liver section), oxidative stress (the enhancement of reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG), separation of thioredoxin (Trx) and thioredoxin-interacting protein (TXNIP), but enhancement of heme oxygenase-1 (HO-1), glutathione S-transferase (GST), and nuclear factor-regulated factor 2 (Nrf2)), and inflammation (up-regulation of cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and nuclear factor kappaB (NF-κB)). However, these changes were alleviated through co-treatment with curcumin. In conclusion, our work provided useful data for further research and new drug exploration of RPS and curcumin. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1935-1943, 2016.


Assuntos
Curcumina/farmacologia , Liliales/química , Rizoma/química , Saponinas/toxicidade , Alanina Transaminase/metabolismo , Animais , Ciclo-Oxigenase 2/metabolismo , Glutationa Transferase/metabolismo , Heme Oxigenase-1/metabolismo , Interleucina-1beta/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade Subcrônica , Regulação para Cima
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