RESUMO
Social recognition encompasses encoding social information and distinguishing unfamiliar from familiar individuals to form social relationships. Although the medial prefrontal cortex (mPFC) is known to play a role in social behavior, how identity information is processed and by which route it is communicated in the brain remains unclear. Here we report that a ventral midline thalamic area, nucleus reuniens (Re) that has reciprocal connections with the mPFC, is critical for social recognition in male mice. In vivo single-unit recordings and decoding analysis reveal that neural populations in both mPFC and Re represent different social stimuli, however, mPFC coding capacity is stronger. We demonstrate that chemogenetic inhibitions of Re impair the mPFC-Re neural synchronization and the mPFC social coding. Projection pathway-specific inhibitions by optogenetics reveal that the reciprocal connectivity between the mPFC and the Re is necessary for social recognition. These results reveal an mPFC-thalamic circuit for social information processing.
Assuntos
Núcleos da Linha Média do Tálamo , Tálamo , Masculino , Camundongos , Animais , Reconhecimento Psicológico , Córtex Pré-Frontal , Vias NeuraisRESUMO
BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .
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COVID-19 , Medicamentos de Ervas Chinesas , Adulto , Humanos , Método Duplo-Cego , Medicamentos de Ervas Chinesas/uso terapêutico , Resultado do TratamentoRESUMO
Saposhnikovia divaricata (Turcz.) Schischk (S. divaricata, Fangfeng) is a herb in the Apiaceae family, and its root has been used since the Western Han Dynasty (202 B.C.). Chromones and coumarins are the pharmacologically active substances in S. divaricata. Modern phytochemical and pharmacological studies have demonstrated their antipyretic, analgesic, anti-inflammatory, antioxidant, anti-tumor, and anticoagulant activities. Technological and analytical strategy theory advancements have yielded novel results; however, most investigations have been limited to the main active substances-chromones and coumarins. Hence, we reviewed studies related to the chemical composition and pharmacological activity of S. divaricata, analyzed the developing trends and challenges, and proposed that research should focus on components' synergistic effects. We also suggested that, the structure-effect relationship should be prioritized in advanced research.
Assuntos
Apiaceae , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Cumarínicos/farmacologia , Apiaceae/química , CromonasRESUMO
Although flavonoids play multiple roles in plant growth and development, the involvement in plant self-incompatibility (SI) have not been reported. In this research, the fertility of transgenic tobacco plants overexpressing the Ginkgo biloba dihydroflavonol 4-reductase gene, GbDFR6, were investigated. To explore the possible physiological defects leading to the failure of embryo development in transgenic tobacco plants, functions of pistils and pollen grains were examined. Transgenic pistils pollinated with pollen grains from another tobacco plants (either transgenic or wild-type), developed full of well-developed seeds. In contrast, in self-pollinated transgenic tobacco plants, pollen-tube growth was arrested in the upper part of the style, and small abnormal seeds developed without fertilization. Although the mechanism remains unclear, our research may provide a valuable method to create SI tobacco plants for breeding.
Assuntos
Ginkgo biloba , Nicotiana , Ginkgo biloba/genética , Nicotiana/fisiologia , Pólen/genética , Polinização/genética , FenótipoRESUMO
The attention mechanism of the Transformer has the advantage of extracting feature correlation in the long-sequence data and visualizing the model. As time-series data, the spatial and temporal dependencies of the EEG signals between the time points and the different channels contain important information for accurate classification. So far, Transformer-based approaches have not been widely explored in motor-imagery EEG classification and visualization, especially lacking general models based on cross-individual validation. Taking advantage of the Transformer model and the spatial-temporal characteristics of the EEG signals, we designed Transformer-based models for classifications of motor imagery EEG based on the PhysioNet dataset. With 3s EEG data, our models obtained the best classification accuracy of 83.31%, 74.44%, and 64.22% on two-, three-, and four-class motor-imagery tasks in cross-individual validation, which outperformed other state-of-the-art models by 0.88%, 2.11%, and 1.06%. The inclusion of the positional embedding modules in the Transformer could improve the EEG classification performance. Furthermore, the visualization results of attention weights provided insights into the working mechanism of the Transformer-based networks during motor imagery tasks. The topography of the attention weights revealed a pattern of event-related desynchronization (ERD) which was consistent with the results from the spectral analysis of Mu and beta rhythm over the sensorimotor areas. Together, our deep learning methods not only provide novel and powerful tools for classifying and understanding EEG data but also have broad applications for brain-computer interface (BCI) systems.
Assuntos
Interfaces Cérebro-Computador , Aprendizado Profundo , Algoritmos , Eletroencefalografia/métodos , Humanos , Imaginação , MovimentoRESUMO
Objective.For high-level peripheral nerve injuryed (PNI) patients with severe sensory dysfunction of upper extremities, identifying the multi-site tactile stimulation is of great importance to provide neurorehabilitation with sensory feedback. In this pilot study, we showed the feasibility of identifying multi-site and multi-intensity tactile stimulation in terms of electroencephalography (EEG).Approach.Three high-level PNI patients and eight non-PNI participants were recruited in this study. Four different sites over the upper arm, forearm, thumb finger and little finger were randomly stimulated at two intensities (both sensory-level) based on the transcutaneous electrical nerve stimulation. Meanwhile, 64-channel EEG signals were recorded during the passive tactile sense stimulation on each side.Main results.The spatial-spectral distribution of brain oscillations underlying multi-site sensory stimulation showed dominant power attenuation over the somatosensory and prefrontal cortices in both alpha-band (8-12 Hz) and beta-band (13-30 Hz). But there was no significant difference among different stimulation sites in terms of the averaged power spectral density over the region of interest. By further identifying different stimulation sites using temporal-spectral features, we found the classification accuracies were all above 89% for the affected arm of PNI patients, comparable to that from their intact side and that from the non-PNI group. When the stimulation site-intensity combinations were treated as eight separate classes, the classification accuracies were ranging from 88.89% to 99.30% for the affected side of PNI subjects, similar to that from their non-affected side and that from the non-PNI group. Other performance metrics, including specificity, precision, and F1-score, also showed a sound identification performance for both PNI patients and non-PNI subjects.Significance.These results suggest that reliable brain oscillations could be evoked and identified well, even though induced tactile sense could not be discerned by the PNI patients. This study have implication for facilitating bidirectional neurorehabilitation systems with sensory feedback.
Assuntos
Tato , Estimulação Elétrica Nervosa Transcutânea , Retroalimentação Sensorial/fisiologia , Dedos , Humanos , Nervos Periféricos , Projetos Piloto , Tato/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodosRESUMO
Because retinitis pigmentosa (RP) has been shown to cause degenerative changes in the entire visual pathway, there is an urgent need to perform longitudinal assessments of RP-induced degeneration and identify imaging protocols to detect this degeneration as early as possible. In this study, we assessed a transgenic rat model of RP by using complementary noninvasive magnetic resonance imaging techniques, namely, proton magnetic resonance spectroscopy (1 H-MRS), to investigate the metabolic changes in RP. Our study demonstrated decreased concentrations and ratios to creatine (Cr) of N-acetylaspartate (NAA), glutamate (Glu), γ-aminobutyric acid (GABA), and taurine (Tau), whereas myo-inositol (Ins) and choline (Cho) were increased in the visual cortex of Royal College of Surgeons (RCS) rats compared with control rats (p < 0.05). Furthermore, with the progression of RP, the concentrations of NAA, Glu, GABA, and Tau, and the ratios of GABA/Cr and Tau/Cr significantly decreased over time, whereas the concentrations of Ins and Cho and the ratio of Ins/Cr significantly increased over time (p < 0.05). In addition, in RCS rats, NAA/Cr decreased significantly from 3 to 4 months postnatal (p < 0.001), and Cho/Cr increased significantly from 4 to 5 months postnatal (p = 0.005). Meanwhile, the 1 H-MRS indicators in 5-month postnatal RCS rats could be confirmed by immunohistochemical staining. In conclusion, with the progression of RP, the metabolic alterations in the visual cortex indicated progressive reprogramming with the decrease of neurons and axons, accompanied by the proliferation of gliocytes.
Assuntos
Retinose Pigmentar , Vias Visuais , Animais , Ácido Aspártico/metabolismo , Colina/metabolismo , Creatina/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Inositol/metabolismo , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Espectroscopia de Prótons por Ressonância Magnética/métodos , Ratos , Retinose Pigmentar/diagnóstico por imagem , Vias Visuais/metabolismo , Ácido gama-AminobutíricoRESUMO
Metastasis is the leading cause of death in breast cancer patients. Osthole, as an active compound detected in the traditional Chinese medicine Wenshen Zhuanggu Formula, has shown a promising anti-metastatic activity in human breast cancer cells, but the underlying mechanisms remain ambiguous. In this study we elucidated the anti-metastatic mechanisms of osthole in highly metastatic breast cancer cells and a zebrafish xenograft model. We showed that the expression of integrin α3 (ITGα3) and integrin ß5 (ITGß5) was upregulated in highly metastatic MDA-MB-231, MDA-MB-231BO breast cancer cell lines but was downregulated in poorly metastatic MCF-7 breast cancer cell line, which might be the key targets of osthole's anti-metastatic action. Furthermore, we showed that knockdown of ITGα3 and ITGß5 attenuated breast cancer cell migration and invasion possibly via suppression of FAK/Src/Rac1 pathway, whereas overexpression of ITGα3 and ITGß5 caused the opposite effects. Consistently, osthole significantly inhibited breast cancer metastasis by downregulating ITGα3/ITGß5 signaling in vitro and in vivo. These results provide new evidence that osthole may be developed as a candidate therapeutic drug for metastatic breast cancer.
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Neoplasias da Mama , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Feminino , Humanos , Invasividade Neoplásica/prevenção & controle , Peixe-ZebraRESUMO
Metastasis accounts for poor prognosis of cancers and related deaths. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) play critical roles in several types of cancer. However, which lncRNAs contribute to metastasis of colon cancer is still largely unknown. In this study, we found that lncRNA LINC01578 was correlated with metastasis and poor prognosis of colon cancer. LINC01578 was upregulated in colon cancer, associated with metastasis, advanced clinical stages, poor overall survival, disease-specific survival, and disease-free survival. Gain-of-function and loss-of-function assays revealed that LINC01578 enhanced colon cancer cell viability and mobility in vitro and colon cancer liver metastasis in vivo. Mechanistically, nuclear factor kappa B (NF-κB) and Yin Yang 1 (YY1) directly bound to the LINC01578 promoter, enhanced its activity, and activated LINC01578 expression. LINC01578 was shown to be a chromatin-bound lncRNA, which directly bound NFKBIB promoter. Furthermore, LINC01578 interacted with and recruited EZH2 to NFKBIB promoter and further repressed NFKBIB expression, thereby activating NF-κB signaling. Through activation of NF-κB, LINC01578 further upregulated YY1 expression. Through activation of the NF-κB/YY1 axis, LINC01578 in turn enhanced its own promoter activity, suggesting that LINC01578 and NF-κB/YY1 formed a positive feedback loop. Blocking NF-κB signaling abolished the oncogenic roles of LINC01578 in colon cancer. Furthermore, the expression levels of LINC01578, NFKBIB, and YY1 were correlated in clinical tissues. Collectively, this study demonstrated that LINC01578 promoted colon cancer metastasis via forming a positive feedback loop with NF-κB/YY1 and suggested that LINC01578 represents a potential prognostic biomarker and therapeutic target for colon cancer metastasis.
Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Retroalimentação Fisiológica , NF-kappa B/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Fator de Transcrição YY1/metabolismo , Animais , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas I-kappa B/metabolismo , Neoplasias Hepáticas/secundário , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Ligação Proteica , RNA Longo não Codificante/genética , Regulação para Cima/genéticaRESUMO
Zebrafish is being increasingly used for metabolism and toxicity assessment. The drugs consumed in zebrafish metabolism studies are far less than those used in rat studies. In our study, zebrafish embryos were exposed to icariin, Baohuoside I (BI), Epimedin A (EA), Epimedin B (EB), Epimedin C (EC), Sagittatoside A (SA), Sagittatoside B (SB), and 2''-O-rhamnosylicariside II (SC), respectively, to examine the toxicity and metabolic profiles of these flavonoids. The order of toxicity was SC, SB > EC, SA > BI, icariin, EA, EB. After 24 h exposure to SB and SC, the mortality of zebrafish larvae reached 100% and yolk sac swollen was obvious. Both SC and SB caused severe hepatocellular vacuolization and liver cells degeneration in adult zebrafish after 15 consecutive days' treatment. The metabolic profiles of these flavonoids with trace amount were also monitored in larvae. BI was the common metabolite shared by icariin, EA, EB, SA, and SB, via deglycosylation. Both BI and SC remained as the prototype in the medium, suggesting that it is hard for BI and SC to cleave the rhamnose residue. EC was metabolized into SC and BI in zebrafish, inferring that SC might be responsible for the toxicity observed in EC group. The metabolites of icariin, EA, EB, EC, and BI in zebrafish larvae coincided with results from rats and intestinal flora. These data support the use of this system as a surrogate in predicting metabolites and hepatotoxicity risk, especially for TCM compound with trace amount.
RESUMO
Mental strength and history of winning play an important role in the determination of social dominance. However, the neural circuits mediating these intrinsic and extrinsic factors have remained unclear. Working in mice, we identified a dorsomedial prefrontal cortex (dmPFC) neural population showing "effort"-related firing during moment-to-moment competition in the dominance tube test. Activation or inhibition of the dmPFC induces instant winning or losing, respectively. In vivo optogenetic-based long-term potentiation and depression experiments establish that the mediodorsal thalamic input to the dmPFC mediates long-lasting changes in the social dominance status that are affected by history of winning. The same neural circuit also underlies transfer of dominance between different social contests. These results provide a framework for understanding the circuit basis of adaptive and pathological social behaviors.
Assuntos
Rede Nervosa/fisiologia , Córtex Pré-Frontal/fisiologia , Predomínio Social , Tálamo/fisiologia , Adaptação Psicológica/fisiologia , Animais , Potenciação de Longa Duração/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Optogenética , Reforço PsicológicoRESUMO
OBJECTIVE: To analyze the correlations between the incidence of tuberculosis and meteorological factors over the same period and previous periods including 1, 2 and 3 years ago, defined according to the Chinese medicine theory of five circuits (Wu Yun) and six qi, to establish medical-meteorological forecast models for the Beijing area of China. METHODS: Data regarding the incidence of tuberculosis between 1990 and 2004 were obtained from the Beijing Center for Disease Control and Prevention, and the data regarding the meteorological factors (including daily average temperatures, wind speeds, precipitations, relative humidities, vapor pressures and low cloud covers) between 1987 and 2004 were collected from the Beijing Meteorological Observatory and analyzed. Descriptive statistics and a back-propagation artificial neural network were adopted to analyze the data. RESULTS: There were significant correlations between the incidence of tuberculosis and the meteorological factors in the corresponding year and previous years. Among these correlations, wind speed was the factor with the strongest influence on tuberculosis (the standardized significance was 100%). Additionally, all prediction models would successfully established, suggesting the use of a collection of meteorological factors spanning from three years ago to the present is superior to the use of single data. CONCLUSIONS: The incidence of tuberculosis in Beijing area is correlated to meteorological factors in the current year and previous years, which verifies the practicality of the theory of five circuits and six qi.
Assuntos
Conceitos Meteorológicos , Tuberculose/epidemiologia , Pequim/epidemiologia , Previsões , Humanos , Medicina Tradicional ChinesaRESUMO
OBJECTIVE: To explore the scientificity of Yunqi theory based on incidence of disease related recognitions such as year evolutive phase, host climatic qi, six climatic factors, celestial manager qi, qi in the earth by analyzing data of hypertension incidence. METHODS: A total of 1,265 inpatients with confirmed first diagnosis as hypertension were recruited at Dongzhimen Hospital, Beijing University of Chinese Medicine from February 4, 1999 to February 4, 2011. Each period (including year evolutive phase, host climatic qi, guest climatic qi) was deducted based on Yun-qi theory. Their ratios of different phases and qi in the total number of hypertension inpatients number were calculated and statistically tested. RESULTS: There was statistical difference in ratios at year evolutive phase, celestial manager qi, and qi in the earth (P < 0.05). CONCLUSION: The incidence of hypertension has certain difference in each period, which is consistent with Yun-qi theory.
Assuntos
Hipertensão/epidemiologia , Medicina Tradicional Chinesa , Qi , Pequim/epidemiologia , Humanos , Incidência , PesquisaRESUMO
Dietary conjugated linoleic acid (CLA) reduces indicators of early renal disease progression and the associated elevated cyclooxygenase (COX) levels in young obese rats with obesity-associated nephropathy (OAN). Therefore, renal function and injury and COX and its metabolites were assessed in obese fa/fa Zucker rats with more advanced renal disease. Obese rats at 16 weeks of age were provided with either cis(c)9, trans(t)11 (fa/fa-9,11) or t10,c12 (fa/fa-10,12) CLA for 8 weeks, and compared to lean (lean-CTL) and obese (fa/fa-CTL) rats provided the control diet without CLA. Obese rats displayed significantly reduced renal function and increased renal injury compared to lean rats. In the obese rat groups, glomerular hypertrophy was reduced in both CLA-supplemented groups. While all other measures of renal function or injury were not different in fa/fa-9,11 compared to fa/fa-CTL rats, the fa/fa-10,12 rats had greater renal hypertrophy, glomerular fibrosis, fibrosis, tubular casts and macrophage infiltration compared to the fa/fa-CTL and fa/fa-9,11 groups. The fa/fa-10,12 group also had elevated levels of renal COX1, which was associated with increased levels of two oxylipins produced by this enzyme, 6-keto-prostaglandin F(1α), and thromboxane B2. Renal linoleic acid and its lipoxygenase products also were lower in obese compared to lean rats, but CLA supplementation had no effect on these or any other lipoxygenase oxylipins. In summary, supplementation with c9,t11 CLA did not improve more advanced OAN and t10,c12 CLA worsened the renal pathology. Altered production of select COX1 derived oxylipins was associated with the detrimental effect of the t10,c12 isomer.
Assuntos
Envelhecimento , Suplementos Nutricionais/efeitos adversos , Rim/patologia , Ácidos Linoleicos Conjugados/efeitos adversos , Obesidade/fisiopatologia , Oxilipinas/agonistas , Insuficiência Renal/etiologia , 6-Cetoprostaglandina F1 alfa/agonistas , 6-Cetoprostaglandina F1 alfa/antagonistas & inibidores , 6-Cetoprostaglandina F1 alfa/metabolismo , Animais , Ciclo-Oxigenase 1/metabolismo , Progressão da Doença , Fibrose , Hipertrofia , Rim/imunologia , Rim/metabolismo , Rim/fisiopatologia , Ativação de Macrófagos , Proteínas de Membrana/agonistas , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Obesidade/imunologia , Oxilipinas/antagonistas & inibidores , Oxilipinas/metabolismo , Ratos Zucker , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Insuficiência Renal/fisiopatologia , Índice de Gravidade de Doença , Tromboxano B2/agonistas , Tromboxano B2/antagonistas & inibidores , Tromboxano B2/metabolismoRESUMO
<p><b>OBJECTIVE</b>To explore the scientificity of Yunqi theory based on incidence of disease related recognitions such as year evolutive phase, host climatic qi, six climatic factors, celestial manager qi, qi in the earth by analyzing data of hypertension incidence.</p><p><b>METHODS</b>A total of 1,265 inpatients with confirmed first diagnosis as hypertension were recruited at Dongzhimen Hospital, Beijing University of Chinese Medicine from February 4, 1999 to February 4, 2011. Each period (including year evolutive phase, host climatic qi, guest climatic qi) was deducted based on Yun-qi theory. Their ratios of different phases and qi in the total number of hypertension inpatients number were calculated and statistically tested.</p><p><b>RESULTS</b>There was statistical difference in ratios at year evolutive phase, celestial manager qi, and qi in the earth (P < 0.05).</p><p><b>CONCLUSION</b>The incidence of hypertension has certain difference in each period, which is consistent with Yun-qi theory.</p>
Assuntos
Humanos , Pequim , Epidemiologia , Hipertensão , Epidemiologia , Incidência , Medicina Tradicional Chinesa , Qi , PesquisaRESUMO
<p><b>OBJECTIVE</b>To analyze the correlations between the incidence of tuberculosis and meteorological factors over the same period and previous periods including 1, 2 and 3 years ago, defined according to the Chinese medicine theory of five circuits (Wu Yun) and six qi, to establish medical-meteorological forecast models for the Beijing area of China.</p><p><b>METHODS</b>Data regarding the incidence of tuberculosis between 1990 and 2004 were obtained from the Beijing Center for Disease Control and Prevention, and the data regarding the meteorological factors (including daily average temperatures, wind speeds, precipitations, relative humidities, vapor pressures and low cloud covers) between 1987 and 2004 were collected from the Beijing Meteorological Observatory and analyzed. Descriptive statistics and a back-propagation artificial neural network were adopted to analyze the data.</p><p><b>RESULTS</b>There were significant correlations between the incidence of tuberculosis and the meteorological factors in the corresponding year and previous years. Among these correlations, wind speed was the factor with the strongest influence on tuberculosis (the standardized significance was 100%). Additionally, all prediction models would successfully established, suggesting the use of a collection of meteorological factors spanning from three years ago to the present is superior to the use of single data.</p><p><b>CONCLUSIONS</b>The incidence of tuberculosis in Beijing area is correlated to meteorological factors in the current year and previous years, which verifies the practicality of the theory of five circuits and six qi.</p>
Assuntos
Humanos , Pequim , Epidemiologia , Previsões , Medicina Tradicional Chinesa , Conceitos Meteorológicos , Tuberculose , EpidemiologiaRESUMO
This article firstly established a new efficient method for screening anti-osteoporosis ingredients, which used two-dimensional zebrafish model combined with hyphenated chromatographic techniques to evaluate anti-osteoporosis activities of epimedin A and its metabolite baohuoside I. Adult zebrafish was used for metabolism of epimedin A in 0.5% DMSO, and LC-MS was used for analysis of the metabolite, which was captured by HPLC, and prednisolone-induced osteoporosis model of zebrafish was used to evaluate the anti-osteoporotic activities of trace amounts of epimedin A and baohuoside I. The results indicated that epimedin A and baohuoside I can prevent prednisolone-induced osteoporosis in zebrafish. The developed method in this paper enables the separation, enrichment and analysis of micro-amount metabolite of epimedin A, and anti-osteoporosis activities in vivo of epimedin A and baohuoside I was simple and efficient screening resorting to zebrafish osteoporosis mode. This paper would provide new ideas and methods for a rapid and early discovery of anti-osteoporosis activities of micro-ingredients and its metabolite of traditional Chinese medicine.
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Flavonoides/farmacologia , Osteoporose/tratamento farmacológico , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/metabolismo , Espectrometria de Massas , Peixe-ZebraRESUMO
OBJECTIVE: To break through the restrictions of the evaluation model and the quantity of compounds by using the two-dimensional zebrafish model combined with chromatographic techniques, and establish a new method for the high-throughput screening of active anti-osteoporosis components. METHOD: According to the research group-related studies and relevant foreign literatures, on the basis of the fact that the zebrafish osteoporosis model could efficiently evaluate the activity, the zebrafish metabolism model could efficiently enrich metabolites and the chromatographic techniques could efficiently separate and analyze components of traditional Chinese medicines, we proposed that the inherent combination of the three methods is expected to efficiently decode in vivo and in vitro efficacious anti-osteoporosis materials of traditional Chinese medicines. RESULT AND CONCLUSION: The method makes it simple and efficient in the enrichment, separation and analysis on components of traditional Chinese medicines, particularly micro-components and metabolites and the screening anti-osteoporosis activity, fully reflects that efficacious materials of traditional Chinese medicines contain original components and metabolites, with characteristic of "multi-components, multi-targets and integral effect", which provides new ideas and methods for the early and rapid discovery of active anti-osteoporosis components of traditional Chinese medicines.
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Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Osteoporose/tratamento farmacológico , Peixe-Zebra/fisiologia , Animais , Cromatografia/métodos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Medicina Tradicional Chinesa/tendências , Osteoporose/fisiopatologia , Fitoterapia/métodos , Fitoterapia/tendências , Reprodutibilidade dos TestesRESUMO
Model organism zebrafish was used to study metabolism of asperosaponin VI from Dipsacus asper Wall. ex Henry for the first time. Metabolic components of asperosaponin VI after exposing to zebrafish for 24 h were identified by high performance liquid chromatography--electrospray mass spectrometry (HPLC-ESI-MS), the separation was performed with a Zorbax C18 column using a binary gradient elution of 0.05% formic acetonitrile--0.05% formic acid water. The quasi-molecular ions of compounds in both negative and positive mode were observed for molecule mass information, and the potential structures were identified by attentive study on the deglycosylation metabolites and one hydroxylation metabolite of asperosaponin VI. The results were highly in consistent with metabolism of asperosaponin VI in rat. It can be concluded that zebrafish model can wonderfully imitate current metabolic model with advantages of small amount of lower cost, far less amount compound, higher efficiency and more simple, and can reflect integrated metabolism results of in vivo method. Zebrafish metabolic model may become a novel organism model for quick predication on metabolism of even mircoamount compound, which can enrich the available models greatly.
Assuntos
Dipsacaceae/química , Saponinas/metabolismo , Peixe-Zebra/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Masculino , Modelos Animais , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Saponinas/isolamento & purificação , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
OBJECTIVE: Suavissimoside R1 was isolated and identified as an active ingredient from Roots of Rubus parvifollus L, which exhibited protective effect on dopaminergic neurons against MPP+ toxicity. METHODS: The protective effects of crude extracts were investigated after mice were treated with 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). According to the protective effects of crude extracts, suavissimoside R1, one kind of triterpenoid saponin, was separated. It was investigated that whether Suavissimoside R1 can protect DA neurons from toxicity induced by MPP+ in rat mesencephalic cultures. RESULTS: Suavissimoside R1 was isolated from Roots of Rubus parvifollus L. Moreover, Suavissimoside R1, in dose of 100 micromol/L, alleviated the death of DA neurons induced by MPP+ obviously. CONCLUSION: These results suggest that suavissimoside R1 possesses potent neuroprotective activity and can be developed to be a potential anti-Parkinson's disease drug worthy for further study.