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Phytochemistry ; 85: 185-93, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23036722


HPLC-PDA-MS and TLC analysis were used to look for minor cytotoxic chlorinated valepotriates from whole plants of Valeriana jatamansi (syn. Valeriana wallichii DC.). This resulted in isolation of 15 chlorinated valepotriates, designated as chlorovaltrates A-O, together with six known analogues, (1S,3R,5R,7S,8S,9S)-3,8-epoxy-1,5-dihydroxyvalechlorine, volvaltrate B, chlorovaltrate, rupesin B, (1S,3R,5R,7S,8S,9S)-3,8-epoxy-1-O-ethyl-5-hydroxyvalechlorine, and (1R,3R,5R,7S,8S,9S)-3,8-epoxy-1-O-ethyl-5-hydroxyvalechlorine. Their structures were elucidated by spectroscopic methods including homo- and heteronuclear two-dimensional NMR experiments. Chlorovaltrates K-N, chlorovaltrate and rupesin B showed moderate cytotoxicity against lung adenocarcinoma (A 549), metastatic prostate cancer (PC-3M), colon cancer (HCT-8) and hepatoma (Bel 7402) cell lines with IC50 values of 0.89-9.76 µM.

Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Iridoides/química , Iridoides/farmacologia , Valeriana/química , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
Interdiscip Sci ; 2(3): 221-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20658334


Quantitative composition-activity relationship (QCAR) study makes it possible to discover active components in traditional Chinese medicine (TCM) and to predict the integral bioactivity by its chemical composition. In the study, 28 samples of Radix Tinosporae were quantitatively analyzed by high performance liquid chromatography, and their analgesic activities were investigated via abdominal writhing tests on mice. Three genetic algorithms (GA) based approaches including partial least square regression, radial basis function neural network, and support vector regression (SVR) were established to construct QCAR models of R. Tinosporae. The result shows that GA-SVR has the best model performance in the bioactivity prediction of R. Tinosporae; seven major components thereof were discovered to have analgesic activities, and the analgesic activities of these components were partly confirmed by subsequent abdominal writhing test. The proposed approach allows discovering active components in TCM and predicting bioactivity by its chemical composition, and is expected to be utilized as a supplementary tool for the quality control and drug discovery of TCM.

Algoritmos , Analgésicos/análise , Medicamentos de Ervas Chinesas/química , Relação Estrutura-Atividade , Tinospora/química , Dor Abdominal , Analgésicos/química , Analgésicos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Descoberta de Drogas , Medicamentos de Ervas Chinesas/farmacologia , Análise dos Mínimos Quadrados , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos ICR , Modelos Biológicos , Raízes de Plantas , Controle de Qualidade , Análise de Regressão , Máquina de Vetores de Suporte
Int J Cancer ; 127(12): 2841-50, 2010 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21351263


The prediction of chemosensitivity is a challenging problem in the management of cancer. In the present study, a metabonomic approach was proposed to assess the feasibility of chemosensitivity prediction in a human xenograft model of gastric cancer. BALB/c-nu/nu mice were transplanted with MKN-45 cell line to establish the xenograft model. The mice were then randomized into treatment group (cisplatin and 5-fluorouracil) and control group (0.9% sodium chloride), and their plasma were collected before treatment. Metabolic profiles of all plasma samples were acquired by using high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer (HPLC/Q-TOF-MS). Based on the data of metabolic profiles and k-Nearest Neighbor algorithm, a prediction model for chemosensitivity was developed and an average accuracy of 90.4% was achieved. In addition, a series of endogenous metabolites, including 1-acyl-lysophosphatidycholines, polyunsaturated fatty acids and their derivatives, were determined as potential indicators of chemosensitivity. In conclusion, our results suggest that the proposed metabonomic approach allows effective chemosensitivity prediction in human xenograft model of gastric cancer. The approach presents a new concept in the chemosensitivtiy prediction of cancer and is expected to be developed as a powerful tool in the personalized cancer therapy.

Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Metabolômica , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Adenocarcinoma/patologia , Animais , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
Rapid Commun Mass Spectrom ; 23(18): 2903-16, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19670339


A high-performance liquid chromatography/electrospray ionization multi-stage tandem mass spectrometry (HPLC/ESI-MS(n)) method was developed to analyze two structurally related groups of Amaryllidaceae alkaloids (AmAs), crinane- and tazettine-type alkaloids, in the species Crinum latifolium and C. asiaticum, as well as different organs of C. latifolium. In ESI-MS(n) spectra of the two types of alkaloids, characteristic fragmentation reactions were observed that allowed us to determine and differentiate them. Based on the fragmentation rules of reference standards, crinane-type alkaloids displayed concurrent neutral loss of C(2)H(5)N (43 u) and C(2)H(6)N (44 u) as well as characteristic ions of m/z 213 and 211, whereas tazettine-type alkaloids exhibited neutral loss of C(3)H(7)N (57 u) [or C(2)H(5)N (43 u), C(3)H(7)NO (73 u)] from the [M+H](+) and [M+H-H(2)O](+) ions. These were supported by quadrupole time-of-flight (Q-Tof)-MS/MS analysis. The chemical complexity of the mixture was resolved by profiling. The compositions of the main crinane- and tazettine-type alkaloids in the above-mentioned species and organs were also compared. Overall, 28 AmAs comprising 14 crinane-type and 14 tazettine-type alkaloids were identified and studied by MS. Among them, 14 AmAs were tentatively characterized from the two species for the first time. This method allowed a rapid analysis of alkaloid distribution and composition of Crinum species, and may also be used for quality control and screening of extracts designated for pharmaceutical application.

Alcaloides de Amaryllidaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Crinum/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Isomerases , Extratos Vegetais/química
NMR Biomed ; 22(6): 601-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19322815


This study proposes an NMR-based metabonomic approach to early prognostic evaluation of sepsis. Forty septic rats receiving cecal ligation and puncture (CLP) were divided into the surviving group and nonsurviving group on day 6, while 20 sham-operated rats served as the control group. Serum samples were collected from septic and sham-operated rats at 12 h after surgery and analyzed using (1)H NMR spectroscopy. Orthogonal partial least squares (OPLS) were applied and showed clustering according to predefined groups, indicating that NMR-based metabolic profiling could reveal pathologic characteristics in the serum of sham-operated, surviving, and nonsurviving septic rats. In addition, six characteristic metabolites including lactate, alanine, acetate, acetoacetate, hydroxybutyrate, and formate, which are mainly involved in energy metabolism, changed markedly in septic rats, especially in the nonsurvivors. Using these metabolites, a predictive model for prognostic evaluation of sepsis was constructed using a radial basis function neural network (RBFNN) with a prediction accuracy of about 87% by test samples. The results indicated that the NMR-based metabonomic approach is a potential technique for the early prognostic evaluation of sepsis.

Metabolômica/métodos , Ressonância Magnética Nuclear Biomolecular , Sepse , Animais , Humanos , Masculino , Prognóstico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Sepse/diagnóstico , Sepse/metabolismo , Sepse/fisiopatologia , Soro/química , Soro/metabolismo , Taxa de Sobrevida
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 29(6): 811-7, 2007 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-18595264


Metabonomics, as a newly developed technique, is expected to be a powerful technique in clinical diagnosis. Metabonomics-based diagnosis involves the global metabolic analysis of body-fluids, determination of biomarkers by multivariate statistic analysis, and establishemen of mathematic models for clinical diagnosis with the aid of pattern recognition. This article reviews the adoption of various analytical and computational strategies, application of metabonomics in clinical diagnosis, and potential challenges and development trends.

Metaboloma , Metabolômica/métodos , Biomarcadores/metabolismo , Líquidos Corporais/metabolismo , Técnicas e Procedimentos Diagnósticos , Humanos , Modelos Teóricos , Análise Multivariada