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1.
Int J Mol Sci ; 25(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38612446

RESUMO

Camellia is an important plant genus that includes well-known species such as C. sinensis, C. oleifera, and C. japonica. The C. sinensis cultivar 'Sangmok', one of Korea's standard types of tea landraces, is a small evergreen tree or shrub. Genome annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of Camellia sinensis cultivar 'Sangmok' was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that 'Sangmok' is closely related to C. sinensis, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in 'Sangmok' were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 'Sangmok'-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The 'Sangmok' genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of 'Sangmok' and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species.


Assuntos
Camellia sinensis , Catequina , Humanos , Metabolismo Secundário , Éxons , Cromossomos Humanos Par 15 , Camellia sinensis/genética , Chá
2.
Int J Mol Sci ; 23(7)2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35409041

RESUMO

Anthocyanins are generally accumulated within a few layers, including the epidermal cells of leaves and stems in plants. Solanum tuberosum cv. 'Jayoung' (hereafter, JY) is known to accumulate anthocyanin both in inner tissues and skins. We discovered that anthocyanin accumulation in the inner tissues of JY was almost diminished (more than 95% was decreased) in tuber induction condition. To investigate the transcriptomic mechanism of anthocyanin accumulation in JY flesh, which can be modulated by growth condition, we performed mRNA sequencing with white-colored flesh tissue of Solanum tuberosum cv. 'Atlantic' (hereafter, 'Daeseo', DS) grown under canonical growth conditions, a JY flesh sample grown under canonical growth conditions, and a JY flesh sample grown under tuber induction conditions. We could identify 36 common DEGs (differentially expressed genes) in JY flesh from canonical growth conditions that showed JY-specifically increased or decreased expression level. These genes were enriched with flavonoid biosynthetic process terms in GO analysis, as well as gene set enrichment analysis (GSEA) analysis. Further in silico analysis on expression levels of anthocyanin biosynthetic genes including rate-limiting genes such as StCHS and StCHI followed by RT-PCR and qRT-PCR analysis showed a strong positive correlation with the observed phenotypes. Finally, we identified StWRKY44 from 36 common DEGs as a possible regulator of anthocyanin accumulation, which was further supported by network analysis. In conclusion, we identified StWRKY44 as a putative regulator of tuber-induction-dependent anthocyanin accumulation.


Assuntos
Antocianinas , Solanum tuberosum , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Transcriptoma
3.
Sci Rep ; 12(1): 997, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-35046506

RESUMO

Mental imagery is an important tool in the cognitive control of emotion. The present study tests the prediction that visual imagery can generate and regulate differential fear conditioning via the activation and prioritization of stimulus representations in early visual cortices. We combined differential fear conditioning with manipulations of viewing and imagining basic visual stimuli in humans. We discovered that mental imagery of a fear-conditioned stimulus compared to imagery of a safe conditioned stimulus generated a significantly greater conditioned response as measured by self-reported fear, the skin conductance response, and right anterior insula activity (experiment 1). Moreover, mental imagery effectively down- and up-regulated the fear conditioned responses (experiment 2). Multivariate classification using the functional magnetic resonance imaging data from retinotopically defined early visual regions revealed significant decoding of the imagined stimuli in V2 and V3 (experiment 1) but significantly reduced decoding in these regions during imagery-based regulation (experiment 2). Together, the present findings indicate that mental imagery can generate and regulate a differential fear conditioned response via mechanisms of the depictive theory of imagery and the biased-competition theory of attention. These findings also highlight the potential importance of mental imagery in the manifestation and treatment of psychological illnesses.


Assuntos
Condicionamento Clássico , Medo/psicologia , Imaginação , Adulto , Estimulação Elétrica , Feminino , Resposta Galvânica da Pele , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino
4.
Nat Commun ; 11(1): 5875, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208749

RESUMO

Senna tora is a widely used medicinal plant. Its health benefits have been attributed to the large quantity of anthraquinones, but how they are made in plants remains a mystery. To identify the genes responsible for plant anthraquinone biosynthesis, we reveal the genome sequence of S. tora at the chromosome level with 526 Mb (96%) assembled into 13 chromosomes. Comparison among related plant species shows that a chalcone synthase-like (CHS-L) gene family has lineage-specifically and rapidly expanded in S. tora. Combining genomics, transcriptomics, metabolomics, and biochemistry, we identify a CHS-L gene contributing to the biosynthesis of anthraquinones. The S. tora reference genome will accelerate the discovery of biologically active anthraquinone biosynthesis pathways in medicinal plants.


Assuntos
Antraquinonas/metabolismo , Genoma de Planta , Proteínas de Plantas/genética , Senna/metabolismo , Antraquinonas/química , Vias Biossintéticas , Cromossomos de Plantas/genética , Cromossomos de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Senna/química , Senna/genética
5.
J Med Food ; 23(7): 793-801, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32380887

RESUMO

Urushiols are amphipathic compounds found in Rhus verniciflua Stokes that exhibit various biological activities. However, their practical use is very restricted due to their contact dermatitis-inducing property. Therefore, we applied the ionization method to remove the allergenic properties of the urushiols and to increase their usability. One of the natural urushiols, 3-pentadecylcatechol (PDC), was heated for 30 min with a solution of H2O and sodium carbonate (Na2CO3). The reaction product was analyzed by electrospray ionization mass spectrometry (ESI-MS). Ionized PDC with an m/z value of 316.9 and complexed PDCs with Na+ of 1 - 3 atoms with m/z values of 340.8, 365.2, and 380.8 were detected. PDC and ionized PDC (3 µmol/3 mg of Vaseline) treatments were applied on the rear of left ear of Sprague-Dawley rats once daily for 10 days. Erythema and swelling were observed on the ear skin treated with PDC, but not in case of ionized PDC. Compared with control, contact hypersensitivity-related biomarkers (neutrophils, eosinophils, immunoglobulin E, and histamine) in the blood were significantly higher only in the PDC-treated group. In addition, Il-1b, Il-6, Tnfα, and Cox-2 mRNA expression levels were dramatically increased in the ear tissue of PDC-treated rats, but in the ionized PDC-treated group, they were similar to those in the control group. Overall, it was confirmed that the allergenic property of the urushiol PDC was removed by ionization. This method is expected to be useful for preventing allergy induction in cooking and food processing using R. verniciflua Stokes.


Assuntos
Catecóis/toxicidade , Hipersensibilidade/prevenção & controle , Espectrometria de Massas por Ionização por Electrospray , Animais , Citocinas/metabolismo , Ratos , Ratos Sprague-Dawley
6.
PLoS One ; 13(12): e0208344, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30533012

RESUMO

Adlay (Coix lacryma-jobi) is a tropical grass that has long been used in traditional Chinese medicine and is known for its nutritional benefits. Recent studies have shown that vitamin E compounds in adlay protect against chronic diseases such as cancer and heart disease. However, the molecular basis of adlay's health benefits remains unknown. Here, we generated adlay gene sets by de novo transcriptome assembly using long-read isoform sequencing (Iso-Seq) and short-read RNA-Sequencing (RNA-Seq). The gene sets obtained from Iso-seq and RNA-seq contained 31,177 genes and 57,901 genes, respectively. We confirmed the validity of the assembled gene sets by experimentally analyzing the levels of prolamin and vitamin E biosynthesis-associated proteins in adlay plant tissues and seeds. We compared the screened adlay genes with known gene families from closely related plant species, such as rice, sorghum and maize. We also identified tissue-specific genes from the adlay leaf, root, and young and mature seed, and experimentally validated the differential expression of 12 randomly-selected genes. Our study of the adlay transcriptome will provide a valuable resource for genetic studies that can enhance adlay breeding programs in the future.


Assuntos
Coix/genética , Análise de Sequência de RNA/métodos , Transcriptoma/genética , Coix/metabolismo , Prolaminas/metabolismo , Isoformas de Proteínas/genética , Sorghum/genética , Vitamina E/metabolismo , Zea mays/genética
7.
J Sep Sci ; 41(12): 2517-2527, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29607619

RESUMO

Papaver plants can produce diverse bioactive alkaloids. Papaver rhoeas Linnaeus (common poppy or corn poppy) is an annual flowering medicinal plant used for treating cough, sleep disorder, and as a sedative, pain reliever, and food. It contains various powerful alkaloids like rhoeadine, benzylisoquinoline, and proaporphine. To investigate and identify alkaloids in the aerial parts of P. rhoeas, samples were collected at different growth stages and analyzed using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A liquid chromatography with mass spectrometry method was developed for the identification and metabolite profiling of alkaloids for P. rhoeas by comparing with Papaver somniferum. Eighteen alkaloids involved in benzylisoquinoline alkaloid biosynthesis were used to optimize the liquid chromatography gradient and mass spectrometry conditions. Fifty-five alkaloids, including protoberberine, benzylisoquinoline, aporphine, benzophenanthridine, and rhoeadine-type alkaloids, were identified authentically or tentatively by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry in samples taken during various growth stages. Rhoeadine alkaloids were observed only in P. rhoeas samples, and codeine and morphine were tentatively identified in P. somniferum. The liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry method can be a powerful tool for the identification of diverse metabolites in the genus Papaver. These results may help understand the biosynthesis of alkaloids in P. rhoeas and evaluate the quality of this plant for possible medicinal applications.


Assuntos
Alcaloides/química , Cromatografia Líquida/métodos , Papaver/química , Extratos Vegetais/química , Espectrometria de Massas em Tandem/métodos , Componentes Aéreos da Planta/química , Plantas Medicinais/química
8.
Plant Biotechnol J ; 16(11): 1904-1917, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29604169

RESUMO

Panax ginseng C. A. Meyer, reputed as the king of medicinal herbs, has slow growth, long generation time, low seed production and complicated genome structure that hamper its study. Here, we unveil the genomic architecture of tetraploid P. ginseng by de novo genome assembly, representing 2.98 Gbp with 59 352 annotated genes. Resequencing data indicated that diploid Panax species diverged in association with global warming in Southern Asia, and two North American species evolved via two intercontinental migrations. Two whole genome duplications (WGD) occurred in the family Araliaceae (including Panax) after divergence with the Apiaceae, the more recent one contributing to the ability of P. ginseng to overwinter, enabling it to spread broadly through the Northern Hemisphere. Functional and evolutionary analyses suggest that production of pharmacologically important dammarane-type ginsenosides originated in Panax and are produced largely in shoot tissues and transported to roots; that newly evolved P. ginseng fatty acid desaturases increase freezing tolerance; and that unprecedented retention of chlorophyll a/b binding protein genes enables efficient photosynthesis under low light. A genome-scale metabolic network provides a holistic view of Panax ginsenoside biosynthesis. This study provides valuable resources for improving medicinal values of ginseng either through genomics-assisted breeding or metabolic engineering.


Assuntos
Genoma de Planta/genética , Panax/genética , Adaptação Biológica/genética , Evolução Biológica , Diploide , Genes de Cloroplastos/genética , Genes de Plantas/genética , Ginsenosídeos/biossíntese , Panax/metabolismo , Tetraploidia
9.
Artigo em Inglês | MEDLINE | ID: mdl-28761499

RESUMO

Cordyceps militaris is used widely as a traditional medicine in East Asia. Although a few studies have attempted to elucidate the anticancer activities of C. militaris, the precise mechanism of C. militaris therapeutic effects is not fully understood. We examined the anticancer activities of C. militaris ethanolic extract (Cm-EE) and its cellular and molecular mechanisms. For this purpose, a xenograft mouse model bearing murine T cell lymphoma (RMA) cell-derived cancers was established to investigate in vivo anticancer mechanisms. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, immunoblotting analysis, and flow cytometric assay were employed to check in vitro cytotoxicity, molecular targets, and proapoptotic action of Cm-EE. Interestingly, cancer sizes and mass were reduced in a C. militaris-administered group. Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm-EE. This result indicated that levels of phosphoglycogen synthase kinase 3ß (p-GSK3ß) and cleaved caspase-3 were increased with orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm-EE treated group compared with a control group. Our results suggested that C. militaris might be able to inhibit cancer growth through regulation of p85/AKT-dependent or GSK3ß-related caspase-3-dependent apoptosis.

10.
Arch Pharm Res ; 39(3): 310-20, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26604105

RESUMO

Black tea has been reported to have anti-obesity effects in both rodents and humans. Gallic acid, an active component of black tea, decomposes quickly into pyrogallol in high-temperature solutions. This study introduced a new, aqueous ethanol extraction of black tea, which resulted in extracts with higher concentrations of gallic acid than conventional black tea extracts prepared by hot-water extraction or hot-ethanol extraction. We confirmed that, compared with the hot-water extract of black tea, the cold-ethanol extract of black tea (CE-BTE) had greater effects on reducing body weight and body fat, improving fatty liver, regulating blood glucose, and reducing blood cholesterol in the high-fat diet-induced obese mouse model. Nonetheless, although CE-BTE significantly reduced fat content, it did not reduce peroxisome proliferator-activated receptor (PPARγ) protein in epididymal fat tissue of HFD mice. We also showed that CE-BTE did not inhibit the function of PPARγ protein to drive adipogenesis of mouse 3T3-L1 preadipocytes. Considering that PPARγ is a master transcription factor not only for adipocyte differentiation, but also for adipose tissue function, such as glucose and lipid metabolism and insulin sensitivity, these results suggest that CE-BTE reduced fat mass and body weight without dampening fat cell homeostasis and insulin sensitivity.


Assuntos
Etanol/química , Extratos Vegetais/farmacologia , Chá/química , Gordura Abdominal/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Dieta Hiperlipídica , Epididimo/metabolismo , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Masculino , Camundongos , Obesidade/induzido quimicamente , Obesidade/prevenção & controle , PPAR gama/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Triglicerídeos/metabolismo
11.
J Neurochem ; 136(6): 1232-1245, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26710244

RESUMO

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the risk of developing it increases with advancing age. In this study, we investigated the protective effects of saikosaponin C (SSc), one of the main bioactive components produced by the traditional Chinese herb, radix bupleuri, the root of Bupleurum falcatum, against AD in various neuronal models. Interestingly, we found that SSc has dual effects on AD by targeting amyloid beta (Aß) and tau, two key proteins in AD. SSc significantly suppressed the release of both Aß peptides 1-40 and 1-42 into cell culture supernatants, though it does not affect BACE1 activity and expression. SSc also inhibited abnormal tau phosphorylation at multiple AD-related residues. Moreover, SSc seems to have beneficial effects on cellular tau function; it accelerated nerve growth factor-mediated neurite outgrowth and increased the assembly of microtubules. In addition, SSc increased synaptic marker proteins such as synaptophysin and PSD-95. Considering its various biological activities, our results suggest that SSc might be a novel therapeutic tool for treating human AD and other neurodegenerative diseases. Tau and amyloid beta are two key features in Alzheimer's disease. Saikosaponin C, an active component of Bupleuri Radix, inhibits abnormal tau phosphorylation and amyloid beta production, thereby promoting synaptic integrity. Saikosaponin C also prevents amyloid beta-induced apoptosis in brain vascular endothelial cells. Therefore, Saikosaponin C may provide a new therapeutic strategy for treatment of neurodegenerative diseases, including Alzheimer's disease.

12.
Gut Liver ; 8(4): 388-93, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25071903

RESUMO

BACKGROUND/AIMS: DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. METHODS: Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. RESULTS: In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. CONCLUSIONS: The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.


Assuntos
Analgésicos/farmacologia , Fármacos Gastrointestinais/farmacologia , Preparações de Plantas/farmacologia , Dor Visceral/prevenção & controle , Analgésicos/administração & dosagem , Animais , Pressão Arterial/efeitos dos fármacos , Colo Descendente/fisiologia , Dilatação/métodos , Fármacos Gastrointestinais/administração & dosagem , Masculino , Limiar da Dor/efeitos dos fármacos , Preparações de Plantas/administração & dosagem , Ratos Sprague-Dawley , Dor Visceral/fisiopatologia
13.
Soc Cogn Affect Neurosci ; 9(12): 2067-77, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24532703

RESUMO

The arousal-biased competition model predicts that arousal increases the gain on neural competition between stimuli representations. Thus, the model predicts that arousal simultaneously enhances processing of salient stimuli and impairs processing of relatively less-salient stimuli. We tested this model with a simple dot-probe task. On each trial, participants were simultaneously exposed to one face image as a salient cue stimulus and one place image as a non-salient stimulus. A border around the face cue location further increased its bottom-up saliency. Before these visual stimuli were shown, one of two tones played: one that predicted a shock (increasing arousal) or one that did not. An arousal-by-saliency interaction in category-specific brain regions (fusiform face area for salient faces and parahippocampal place area for non-salient places) indicated that brain activation associated with processing the salient stimulus was enhanced under arousal whereas activation associated with processing the non-salient stimulus was suppressed under arousal. This is the first functional magnetic resonance imaging study to demonstrate that arousal can enhance information processing for prioritized stimuli while simultaneously impairing processing of non-prioritized stimuli. Thus, it goes beyond previous research to show that arousal does not uniformly enhance perceptual processing, but instead does so selectively in ways that optimizes attention to highly salient stimuli.


Assuntos
Nível de Alerta/fisiologia , Viés , Encéfalo/fisiologia , Comportamento Competitivo/fisiologia , Medo/fisiologia , Estimulação Acústica , Adolescente , Adulto , Encéfalo/irrigação sanguínea , Condicionamento Clássico , Feminino , Resposta Galvânica da Pele/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Estimulação Luminosa , Tempo de Reação , Adulto Jovem
14.
Water Sci Technol ; 68(2): 479-85, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23863444

RESUMO

Biological reuse of spent sulfidic caustic (SSC) originating from oil refineries is a promising method for the petrochemical industry because of low handling cost. SSC typically contains high concentrations of sulfur, with the most dominant sulfur compounds being sulfide (S(2-)). SSC is also characterized by a high pH and elevated alkalinity up to 5-15% by weight. Because of these characteristics, SSC can be used for denitrification of NO3(-)-N in the biological nitrogen removal process as both the electron donor and buffering agent in sulfur-utilizing autotrophic denitrification. In this study, two kinds of SSC (SSC I, SSC II) produced from two petrochemical companies were used for autotrophic denitrification in a field-scale wastewater treatment plant (WWTP). The effluent total nitrogen (TN) concentration in this process was about 10.5 mg/L without any external carbon sources and the nitrification efficiency was low, about 93.0%, because of alkalinity deficiency in the influent. The injection of SSC I, but not SSC II, promoted nitrification efficiency, which was attributed to the difference in the NaOH/S ratio between SSC I and II. SSC was injected based on sulfide concentration of SSC required to denitrify NO3(-)-N in the WWTP. SSC I had higher NaOH/S than SSC II and thus could supply more alkalinity for nitrification than SSC II. On the other hand, additional TN removal of about 9.0% was achieved with the injection of both SSCs. However, denitrification efficiency was not proportionally increased with increasing SSC injection because of NO3(-)-N deficiency in the anoxic tank due to the limited capacity of the recycling pump. For the same reason, sulfate concentration, which is the end product of sulfur-utilizing autotrophic denitrificaiton in the effluent, was also not increased with increasing SSC injection.


Assuntos
Resíduos Industriais , Sulfetos/metabolismo , Eliminação de Resíduos Líquidos/métodos , Processos Autotróficos , Análise da Demanda Biológica de Oxigênio , Cáusticos , Desnitrificação , Elétrons , Nitratos/metabolismo , Nitrogênio/metabolismo , Oxirredução , Petróleo , Compostos de Amônio Quaternário/metabolismo , Sulfatos/metabolismo , Poluentes Químicos da Água/metabolismo
15.
J Gastroenterol Hepatol ; 27(4): 766-72, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21916991

RESUMO

BACKGROUND AND AIM: DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, has strong prokinetic effects, and enhances gastric compliance in conscious dogs. In this study, the effects of DA-9701 on gastric accommodation were studied in conscious dogs. METHODS: Beagle dogs with an implanted gastric cannula in the stomach were used in this study. After an overnight fast, the dogs received DA-9701 orally, or served as a positive control that received sumatriptan or a negative control before ingestion of a meal. The basal and postprandial gastric volumes were monitored at a constant operating pressure using an electronic barostat. To investigate the long-lasting effects on increased postprandial gastric volume, the area under the volume versus time curve (AUC) was calculated. RESULTS: DA-9701 significantly increased the basal gastric volume compared to the negative controls (P < 0.05); the effects were comparable to sumatriptan. DA-9701 and sumatriptan significantly increased gastric accommodation compared to the negative control (P < 0.05). In the negative control, the gastric volume reached the maximal volume 40 min after the meal, and then gradually decreased. However, with DA-9701, the increased gastric volume remained significantly elevated for 60 min postprandially (P < 0.05). DA-9701 significantly increased the value of AUC compared to the negative control; this was observed during both the early and late postprandial phases (P < 0.05). CONCLUSIONS: A novel prokinetic agent, DA-9701, improved gastric accommodation by increasing the postprandial gastric volume; these effects persisted for 60 min after a meal.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Preparações de Plantas/farmacologia , Estômago/anatomia & histologia , Estômago/efeitos dos fármacos , Análise de Variância , Animais , Área Sob a Curva , Cães , Feminino , Tamanho do Órgão/efeitos dos fármacos , Período Pós-Prandial , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Estômago/fisiologia , Sumatriptana/farmacologia , Fatores de Tempo
16.
J Pharmacol Exp Ther ; 338(3): 917-24, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21659472

RESUMO

Because delayed gastric emptying and impaired gastric accommodation are regarded as pathophysiological mechanisms underlying functional dyspepsia (FD), prokinetics and fundic relaxants have been suggested as a new treatment for FD. We isolated tetrahydroberberine (THB), an isoquinoline alkaloid (5,8,13,13a-tetrahydro-9,10-dimethoxy-6H-benzo[g]-1,3-benzodioxolo[5,6-a]quinolizine) from Corydalis tuber, and found that it has micromolar affinity for dopamine D(2) (pK(i) = 6.08) and 5-HT(1A) (pK(i) = 5.38) receptors but moderate to no affinity for other relevant serotonin receptors (i.e., 5-HT(1B), 5-HT(1D), 5-HT(3), and 5-HT(4); pK(i) < 5.00). Oral administration of THB not only resulted in significantly accelerated gastric emptying of normal rats in a bell-shaped relationship, with a maximal efficacy at a dose of 30 µg/kg, but also restored the delayed gastric emptying caused by apomorphine, which might be mediated by an antidopaminergic effect. Data from electromyography indicated enhanced motor function of the upper gastrointestinal tract by THB, which occurred through strengthening contractility and shortening the contraction interval. Furthermore, in rats stressed by repeated restraint, a significantly higher shift in the pressure-volume curve by THB (10 µg/kg, p < 0.05), which was inhibited by [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635), a 5-HT(1A) antagonist, and N(ω)-nitro-l-arginine methyl ester, a nitric-oxide synthase inhibitor but not a vasoactive intestinal peptide antagonist, was observed. Oral administration of THB resulted in a drastic increase of gastric accommodation in Beagle dogs. Area under the volume versus time curve was increased significantly by THB (30 µg/kg, p < 0.01) and comparable with that of sumatriptan (3 mg/kg), a potent fundic relaxant. Taken together, our data suggested that THB, with D(2) receptor antagonist and 5-HT(1A) receptor agonist properties, has significant potential as a therapeutic for treatment of FD.


Assuntos
Berberina/análogos & derivados , Corydalis/química , Motilidade Gastrointestinal/efeitos dos fármacos , Animais , Berberina/farmacologia , Ligação Competitiva/efeitos dos fármacos , Células CHO , Cricetinae , Cricetulus , Cães , Dispepsia/complicações , Dispepsia/tratamento farmacológico , Eletromiografia , Fundo Gástrico/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Relaxamento Muscular/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Estimulação Química
17.
Biol Pharm Bull ; 33(6): 958-62, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20522959

RESUMO

The aim of this study was to evaluate the prokinetic and gastric-relaxing effects of the isoquinoline alkaloid corydaline, which was extracted from Corydalis tubers (CT). Corydaline is a marker compound used for quality control of DA-9701, a prokinetic agent formulated from extracts of Pharbitidis semen and Corydalis tuber that is currently in clinical trials in Korea for the treatment of functional dyspepsia (FD). DA-9701 was previously reported to be a potential therapeutic agent for the treatment of abnormalities in gastrointestinal motor function in FD patients; however, the therapeutic effects of corydaline on FD have yet to be demonstrated in an in vivo study. In the current study, oral administration of corydaline not only significantly accelerated gastric emptying in normal rats but also improved delayed gastric emptying to near normal levels. Furthermore, corydaline induced significant gastric relaxation, shifting the pressure-volume curve towards higher volumes compared to controls. These results suggest that corydaline promotes gastric emptying and small intestinal transit and facilitates gastric accommodation.


Assuntos
Alcaloides de Berberina/farmacologia , Corydalis/química , Esvaziamento Gástrico/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Trânsito Gastrointestinal/efeitos dos fármacos , Gastroparesia/tratamento farmacológico , Extratos Vegetais/farmacologia , Administração Oral , Animais , Apomorfina , Alcaloides de Berberina/isolamento & purificação , Alcaloides de Berberina/uso terapêutico , Cães , Gastroparesia/induzido quimicamente , Masculino , Modelos Animais , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Preparações de Plantas , Tubérculos , Ratos , Ratos Sprague-Dawley
18.
Phytomedicine ; 15(10): 836-43, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18490147

RESUMO

To develop a therapeutic for functional dyspepsia (FD), a prokinetic agent, DA-9701 has been newly formulated with Pharbitis Semen and Corydalis Tuber and we evaluated the gastroprokinetic effects of DA-9701 in comparison with conventional prokinetics. Oral administration with DA-9701 not only significantly accelerated gastric emptying in normal rats but also restored the delayed gastric emptying caused by apomorphine and cisplatin up to almost normal levels. For gastrointestinal transit, DA-9701 caused FITC-dextran to travel a significantly longer distance than the control, and in the delayed GI transit models induced by laparotomy and atopine, DA-9701 considerably increased the values of mean geometric center (MGC), while the conventional prokinetics rarely showed significant effects. Furthermore, DA-9701 drastically increased the gastric accommodation in Beagle dogs, shifting the pressure-volume curve toward considerably higher volume compared to the control, which was comparable to that of cisapride. These results indicate that DA-9701 has potential as a safe and effective therapeutic for FD patients with abnormalities in GI motor function.


Assuntos
Corydalis/química , Esvaziamento Gástrico/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Ipomoea/química , Preparações de Plantas/farmacologia , Administração Oral , Animais , Cães , Descoberta de Drogas , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/isolamento & purificação , Preparações de Plantas/isolamento & purificação , Ratos
20.
Artigo em Inglês | MEDLINE | ID: mdl-15055931

RESUMO

Biofilms occurring in seepage groundwater contaminated with petroleum in an urban subway drainage system were characterized. The development of biofilms was observed only in the sites where petroleum-contaminated groundwater had seeped or was seeping. Moreover, the conditions of the biofilms such as color and development extent were influenced by the amount of spilled petroleum: By increasing the amount of spilled petroleum, the amount of biofilms increased and its color whitened. It deteriorated and became dark-brown if the contaminated groundwater did not seep any more. These facts indicate that the biofilms can be used as a preliminary indicator to identify the locations of fuel contaminated sumps and seeps without a more detailed assessment such as instrumental analysis. The biofilms were capable of degrading petroleum at 15 degrees C, which is similar to the average temperature of the seepage groundwater. Filamentous bacteria, Sphaerotilus spp., were isolated from the biofilms. It is considered that these bacteria are responsible for the development of biofilms in the seepage groundwater contaminated with petroleum because they can secrete extracellular polymeric substances.


Assuntos
Biofilmes , Petróleo , Sphaerotilus/classificação , Poluentes Químicos da Água , Biodegradação Ambiental , Humanos , Sphaerotilus/isolamento & purificação , Sphaerotilus/metabolismo
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