Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
1.
Phytomedicine ; 102: 154164, 2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35597026

RESUMEN

BACKGROUND: Many extracts and purified alkaloids of M. cordata (Papaveraceae family) have been reported to display promising anti-tumor effects by inhibiting cancer cell growth and inducing apoptosis in many cancer types. However, no evidence currently exists for anti-pancreatic cancer activity of alkaloids extracted from M. cordata, including a novel alkaloid named 6­methoxy dihydrosphingosine (6-Methoxydihydroavicine, 6-ME) derived from M. cordata fruits. PURPOSE: The aim of this study was to investigate the anti-tumor effects of 6-ME on PC cells and the underlying mechanism. METHODS: CCK-8, RTCA, and colony-formation assays were used to analyze PC cell growth. Cell death ratios, changes in MMP and ROS levels were measured by flow cytometry within corresponding detection kits. A Seahorse XFe96 was employed to examine the effects of 6-ME on cellular bioenergetics. Western blot and q-RT-PCR were conducted to detect changes in target molecules. RESULTS: 6-ME effectively reduced the growth of PC cells and promoted PCD by activating RIPK1, caspases, and GSDME. Specifically, 6-ME treatment caused a disruption of OAA metabolism and increased ROS production, thereby affecting mitochondrial homeostasis and reducing aerobic glycolysis. These responses resulted in mitophagy and RIPK1-mediated cell death. CONCLUSION: 6-ME exhibited specific anti-tumor effects through interrupting OAA metabolic homeostasis to trigger ROS/RIPK1-dependent cell death and mitochondrial dysfunction, suggesting that 6-ME could be considered as a highly promising compound for PC intervention.


Asunto(s)
Alcaloides , Antineoplásicos , Caspasas , Equol/análogos & derivados , Ácido Oxaloacético , Neoplasias Pancreáticas , Especies Reactivas de Oxígeno , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Alcaloides/farmacología , Antineoplásicos/farmacología , Caspasas/metabolismo , Muerte Celular/efectos de los fármacos , Equol/farmacología , Humanos , Ácido Oxaloacético/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Papaveraceae/química , Especies Reactivas de Oxígeno/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo
2.
Eur J Cell Biol ; 101(2): 151223, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35405463

RESUMEN

BACKGROUND: The abnormal differentiation of Th17 cells aggravates ulcerative colitis (UC). Antimicrobial peptides (AMPs) exert pivotal protection functions against UC. KT2 is a cationic AMP that mediates colon cancer development. However, KT2's function in UC remains unclear. METHODS: The UC mouse model was induced by administering 2.5% dextran sulfate sodium, and the mice were given an enema of KT2. KT2's function in UC and Th17 cell differentiation in vivo was evaluated through various molecular experiments. The KT2's function in Th17 cell differentiation in vitro was evaluated by the proportion of CD4+ IL-17+ T cells, IL-17 levels, and RORγt expression levels. Meanwhile, the mechanism was assessed through quantitative real-time PCR, various loss-of-function assays, and dual-luciferase reporter gene assay. RESULTS: KT2 restrained Th17 cell differentiation in both in vivo and in vitro UC models and slowed the UC process. KT2 elevated miR-302c-5p expression, as well as restrained Th17 cell differentiation by increasing miR-302c-5p. Meanwhile, miR-302c-5p interacted with the signal transducer and activator of transcription 3 (STAT3) and negatively regulated its expression. Furthermore, our data revealed that KT2 restrained the activation of STAT3 by elevating miR-302c-5p, thereby inhibiting Th17 cell differentiation. CONCLUSION: KT2 alleviates UC by repressing Th17 cell differentiation through the miR-302c-5p/STAT3 axis.


Asunto(s)
Colitis Ulcerosa , MicroARNs , Animales , Diferenciación Celular , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/genética , Colitis Ulcerosa/metabolismo , Interleucina-17/efectos adversos , Interleucina-17/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Células Th17/metabolismo
3.
Food Chem ; 371: 131200, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34624741

RESUMEN

Fresh shiitake (Lentinus edodes) is prone to brown, pileus-opening and flavor-loss during storage. Therefore, it is important to find an effective preservation method for fresh shiitake. Negative air ions (NAI) are negatively-charged molecules or atoms in the air, and can affect the physiological metabolism of live cells and be conveniently used with low cost. In this study, NAI treatment was performed at different times and the physico-chemical characteristics, microstructure, membrane potential and energy metabolism of shiitake were determined during storage. Results showed that NAI treatment for 40 min could reduce 29% of browning index and maintain the hardness of shiitake. NAI treatment groups had higher content of sweetness amino acids, umami amino acids, 5'-IMP, eight-carbon alcohols compounds and cyclic sulfides compounds than the control, and comprehensive quality of the group being treated for 40 min was the best. The mitochondria of shiitake swelled and the membrane potential decreased after being treated by NAI. However, NAI treatment for 40 min could improve the contents of ATP and ADP, maintain a relatively stable energy charge level, and promote energy utilization of shiitake during storage. The results demonstrated that NAI treatment had the potential to improve the quality shiitake during storage.


Asunto(s)
Hongos Shiitake , Aminoácidos , Aromatizantes , Iones , Gusto
4.
Small ; 17(10): e2007090, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33464716

RESUMEN

Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has shown a great prospect in cancer treatment. However, its therapeutic effect is restricted by the depth of light penetration in tissue and tumor hypoxia environment. Herein, inspired by the specific response of nanozymes to the tumor microenvironment (TME), a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform (denoted as FePc/HNCSs) is constructed using hollow nitrogen-doped carbon nanospheres (HNCSs) and iron phthalocyanine (FePc). FePc/HNCSs simultaneously exhibit peroxidase (POD)- and catalase (CAT)-like activities, which not only can convert endogenous hydrogen peroxide (H2 O2 ) into highly toxic hydroxyl radicals (•OH) for catalytic therapy, but also decompose H2 O2 to oxygen (O2 ) to enhance O2 -dependent PDT. In addition, their enzyme-like activities are significantly enhanced under light irradiation. Combining with the excellent photothermal effect, FePc/HNCSs realize a high tumor inhibition rate of 96.3%. This strategy opens a new horizon for exploring a more powerful tumor treatment nanoplatform.


Asunto(s)
Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/tratamiento farmacológico , Fototerapia , Hipoxia Tumoral , Microambiente Tumoral
5.
Int J Med Mushrooms ; 22(2): 133-144, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32479002

RESUMEN

Total phenolics, flavonoids, and polysaccharides, and individual ganoderic acid (GA) contents, antioxidant capacity, and transcription levels of key enzyme genes involved in GA biosynthesis in pileus and stipes of Ganoderma lucidum fruiting body at different growth stages were investigated in this study. Results showed that the highest total phenolics and total flavonoids contents were determined in stipes at spore maturity stage, resulting in high antioxidant activity, while the highest total polysaccharide content was found in pileus at the same stage. The pileus contained more GA than the stipes, and higher contents of ganoderic acid A and D were found at fruiting body mature stage while that of ganoderic acid B, C2, and G were found at bud elongation stage. Results from quantitative real-time PCR indicated that higher gene transcription levels of hydroxyl methylglutaryl-CoA reductase (hmgr), farnesyl pyrophosphate synthase (fps), squalene synthase (sqs), and oxidosqualene cyclase (osc) were found in pileus at bud elongation stage. Our findings will be helpful for understanding the biosynthesis of bioactive components and determining the harvest time for the desired G. lucidum fruiting bodies.


Asunto(s)
Antioxidantes/análisis , Cuerpos Fructíferos de los Hongos/química , Proteínas Fúngicas/genética , Reishi/química , Triterpenos/metabolismo , Antioxidantes/metabolismo , Farnesil Difosfato Farnesil Transferasa/genética , Flavonoides/metabolismo , Cuerpos Fructíferos de los Hongos/enzimología , Cuerpos Fructíferos de los Hongos/genética , Cuerpos Fructíferos de los Hongos/crecimiento & desarrollo , Geraniltranstransferasa/genética , Hidroxibenzoatos/metabolismo , Hidroximetilglutaril-CoA Reductasas/genética , Transferasas Intramoleculares/genética , Polisacáridos/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reishi/enzimología , Reishi/genética , Reishi/crecimiento & desarrollo , Triterpenos/análisis
6.
Zhen Ci Yan Jiu ; 42(3): 189-96, 2017 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-29071973

RESUMEN

OBJECTIVE: To observe the effect of transcutaneous otopoint electrostimulaiton (TCOES) on seizure frequency, immunoreactivity of hippocampal gliocytes and expression of proinflammatory cytokine interleukin-6(IL-6) and anti-inflammatory cytokine IL-10 in chronic temporal lobe epilepsy (CTLE) rats, so as to investigate its antiepileptic mechanism. METHODS: Thirty-six SD rats were randomly divided into control, model and TCOES groups (n=12 in each group). The CTLE model was established by intraperitoneal injection (i.p.i.) of lithium chloride (127.2 mg/kg), scopolamine (1 mg/kg, 20 h after the 1st injection) and pilocarpine (10 mg/kg, 30 min after scopolamine injection). Rats of the control group were treated by i.p.i. of normal saline. TCOES (1 mA, 20 Hz) was applied to bilateral otopoint "Heart"-"Lung"-"Subcortex" region for 20 min, once daily for 6 weeks. The epileptic attack was observed by a video monitoring system. The numbers of ionized calcium-binding adapter molecule-1 (Iba 1)-labeled microgliacytes and glial fibrillary acidic protein (GFAP)-labeled astrocytes in the CA 1 and CA 3 regions of hippocampus were counted under light microscope after immunostaining, and the expression levels of hippocampal IL-6 and IL-10 proteins and genes were determined by immunofluorescence and quantitative real-time PCR, respectively. RESULTS: After TCOES intervention, the seizure frequency was significantly decreased in comparison with pre-treatment(P<0.05), modeling-induced dramatic increase of the numbers of microgliacytes and astrocytes,IL-6 immunoactivity in the hippocampal CA 1 and CA 3 regions, and IL-6 mRNA expression in the hippocampus were significantly suppressed (P<0.05), and hippo-campal IL-10 immunoactivity and mRNA expression were considerably up-regulated in comparison with the model group (P<0.05). CONCLUSIONS: TCOES intervention has an antiepileptic effect in CTLE rats, which may be associated with its effects in suppressing gliocyte proliferation, suppressing the expression of proinflammatory cytokine IL-6, and up-regulaiting the expression of anti-inflammatory cytokine IL-10 in the hippocampus.


Asunto(s)
Electroacupuntura , Epilepsia del Lóbulo Temporal/terapia , Hipocampo/citología , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Neuroglía/citología , Puntos de Acupuntura , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Ratas , Ratas Sprague-Dawley
7.
Acupunct Med ; 35(4): 276-283, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28600329

RESUMEN

OBJECTIVE: Acupuncture therapy effectively reduces post-surgical pain, but its mechanism of action remains unclear. The aim of this study was to investigate whether expression of γ-aminobutyric acid (GABA) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the primary sensory neurons of cervical dorsal root ganglia (DRG) are involved in electroacupuncture (EA)-induced analgesia in a rat model of incisional neck pain. METHODS: The pain model was established by making a longitudinal midline neck incision in 60 rats. Another 15 rats underwent sham surgery (normal group). Post-incision, 15 rats remained untreated (model group) and 45 rats underwent EA (frequency 2/100 Hz, intensity 1 mA) at bilateral LI18, LI4-PC6 or ST36-GB34 (n=15 each) for 30 min at 4 hours, 24 hours, and 48 hours post-surgery, followed by thermal pain threshold (PT) measurement. 30 min later, the rats were euthanased and cervical (C3-6) DRGs removed for measurement of immunoreactivity and mRNA expression of SP/CGRP and the GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67). RESULTS: Thermal PT was significantly lower in the model group versus the normal group and increased in the LI18 and LI4-PC6 groups but not the ST36-GB34 group compared with the model group. Additionally, EA at LI18 and LI4-PC6 markedly suppressed neck incision-induced upregulation of mRNA/protein expression of SP/CGRP, and upregulated mRNA/protein expression of GAD67 in the DRGs of C3-6 segments. CONCLUSIONS: EA at LI18/LI4-PC6 increases PT in rats with incisional neck pain, which is likely related to downregulation of pronociceptive mediators SP/CGRP and upregulation of the inhibitory transmitter GABA in the primary sensory neurons of cervical DRGs.


Asunto(s)
Analgesia por Acupuntura , Péptido Relacionado con Gen de Calcitonina/genética , Electroacupuntura , Ganglios Espinales/metabolismo , Dolor de Cuello/cirugía , Dolor Postoperatorio/terapia , Sustancia P/genética , Ácido gamma-Aminobutírico/metabolismo , Puntos de Acupuntura , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Humanos , Masculino , Dolor Postoperatorio/etiología , Dolor Postoperatorio/genética , Dolor Postoperatorio/metabolismo , Ratas , Ratas Sprague-Dawley , Sustancia P/metabolismo
8.
Zhen Ci Yan Jiu ; 41(4): 283-90, 2016 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-29071921

RESUMEN

OBJECTIVE: To observe the effect of transcutaneous otopoint electrostimulation (TCOES) on behavior and expression of hippocampal interleukin-1 ß (IL-1 ß) and tumor necrosis factor-α (TNF-α) expression in lithium-pilocarpine induced chronic spontaneous temporal lobe epilepsy (TLE) rats, so as to investigate its antiepileptic mechanism. METHODS: Thirty-six SD rats were randomly divided into control, model and TCOES groups (n=12 in each group). The epilepsy model was established by intraperitoneal injection of lithium chloride (127.2 mg/kg), scopolamine(1 mg/kg, 20 h after the 1st injection) and pilocarpine (10 mg/kg, 30 min after scopolamine injection). Rats of the control group were treated by injection of normal saline(i.p.i.). Transcutaneous electrostimulation (1 mA, 20 Hz) was applied to bilateral otopoints "Heart" "Lung" and "Subcortex" for 20 min, once daily for 6 weeks except the weekends. The behavior reactions were observed by a video monitoring system. The expression of IL-1 ß and TNF-α proteins and genes in the hippocampus were determined by immunofluorescence and quantitative real-time PCR, separately. RESULTS: Behavioral observation showed that after TCOES intervention, the frequency of epilepsy attack was significantly decreased in comparison with pre-treatment (P<0.05). Immunofluorescence and real-time PCR showed that compared with the control group, the immunoactivity of IL-1 ß and TNF-α in both hippocampal CA 1 and CA 3 regions and hippocampal IL-1 ß and TNF-α gene expression were obviously increased in the model group (P<0.05, P<0.01). Following TCOES, the increased hippocampal IL-1 ß and TNF-α and IL-1 ß mRNA and TNF-α mRNA expression levels were all suppressed (P<0.05, P<0.01). CONCLUSIONS: TCOES intervention has an antiepileptogenic effect in temporal lobe epilepsy rats, which may be related to its effects in down-regulating expression of proinflammatory cytokine IL-1 ß and TNF-α in the hippocampus.


Asunto(s)
Electroacupuntura , Epilepsia del Lóbulo Temporal/terapia , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Puntos de Acupuntura , Animales , Epilepsia del Lóbulo Temporal/genética , Epilepsia del Lóbulo Temporal/metabolismo , Humanos , Interleucina-1beta/genética , Masculino , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética
9.
Arch Pharm Res ; 37(12): 1530-7, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24737396

RESUMEN

Polysaccharides from Ganoderma lucidum showed multiple biological activities, such as immuno-modulating, antitumor, antioxidant, and hepatoprotective activity, etc. Adlay oil was added into the media to enhance polysaccharide production by submerged culture of G. lucidum in this work. The results revealed the optimal concentration of adlay oil was 1.5 % for polysaccharide production of G. lucidum. Analysis of the polysaccharide components confirmed that no novel components were biosynthesized by the addition of adlay oil. The main fraction of extracellular polysaccharide, GLEP-2, was isolated from the submerged culture broth of G. lucidum by ethanol precipitation, filtration, DEAE cellulose-52 and Sepharose CL-6B chromatography. GLEP-2, which was composed of glucose, galactose, mannose, arabinose, and rhamnose in a ratio of 332:55:32:13:3 respectively, had an average molecular weight of ~2.08 × 10(4) Da. The bioactivity tests demonstrated that GLEP-2 enhanced the T lymphocyte proliferation significantly at a concentration of 200 µg/mL and B lymphocyte proliferation at lower concentrations of 50 µg/mL. The results suggest polysaccharides from the submerged culture of G. lucidum are potential candidates for further development and possible commercial applications, especially in the pharmaceutical and functional foods industries.


Asunto(s)
Medicina Tradicional China , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Reishi/química , Reishi/crecimiento & desarrollo , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Coix/química , Relación Dosis-Respuesta a Droga , Espectroscopía de Resonancia Magnética , Ratones Endogámicos BALB C , Micelio/efectos de los fármacos , Micelio/crecimiento & desarrollo , Aceites de Plantas/farmacología , Reishi/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Linfocitos T/citología , Linfocitos T/efectos de los fármacos
10.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(10): 2808-14, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25739230

RESUMEN

As one very precious traditional Chinese medicine (TCM), Huoshan Dendrobium has not only high price, but also significant pharmaceutical efficacy. However, different species of Huoshan Dendrobium exhibit considerable difference in pharmaceutical efficacy, so rapid and absolutely non-destructive discrimination of Huoshan Dendrobium nobile according to different species is crucial to quality control and pharmaceutical effect. In this study, as one type of miniature near-infrared (NIR) spectrometer, MicroNIR 1700 was used for absolutely nondestructive determination of NIR spectra of 90 batches of Dendrobium from five species of differ- ent commodity grades. The samples were intact and not smashed. Soft independent modeling of class analogy (SIMCA) pattern recognition based on principal component analysis (PCA) was used to classify and recognize different species of Dendrobium samples. The results indicated that the SIMCA qualitative models established with pretreatment method of standard normal variate transformation (SNV) in the spectra range selected by Qs method had 100% recognition rates and 100% rejection rates. This study demonstrated that a rapid and absolutely non-destructive analytical technique based on MicroNIR 1700 spectrometer was developed for successful discrimination of five different species of Huoshan Dendrobium with acceptable accuracy.


Asunto(s)
Dendrobium/clasificación , Espectroscopía Infrarroja Corta , Medicamentos Herbarios Chinos/análisis , Plantas Medicinales/clasificación , Análisis de Componente Principal , Control de Calidad
11.
J Pharm Anal ; 2(6): 422-430, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29403777

RESUMEN

A simple, sensitive and accurate method based on high performance liquid chromatography (HPLC) with diode array detector (DAD) was developed and validated for systematic quality evaluation of one type of traditional Chinese medicine preparations named Xinkeshu (XKS) tablet. In this study, the chromatographic fingerprints of XKS tablet were developed first, 23 peaks were selected as the common peaks to evaluate the similarities among different batches of XKS samples, which were manufactured in a long time span of three years. Additionally, simultaneous quantification of six markers in XKS tablet, including Danshensu, Protocatechuic aldehyde, Puerarin, Daidzin, Salvianolic acid B and Daidzein, was performed. The validation results showed that the developed method was specific, accurate, precise and robust. The preliminary explanation on why a close similarity between fingerprints did not exactly mean similar contents of chemical components in samples was given. The contribution of each chromatographic peak to similarity was also evaluated. The developed method offers an efficient, reliable and practical approach for systematic quality evaluation of XKS tablet.

12.
PLoS One ; 6(7): e22120, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21789223

RESUMEN

Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules in innate immunity. Cathelicidin-BF has been purified from the snake venoms of Bungarus fasciatus and it is the first identified cathelicidin antimicrobial peptide in reptiles. In this study, cathelicidin-BF was found exerting strong antibacterial activities against Propionibacterium acnes. Its minimal inhibitory concentration against two strains of P. acnes was 4.7 µg/ml. Cathelicidin-BF also effectively killed other microorganisms including Staphylococcus epidermidis, which was possible pathogen for acne vulgaris. Cathelicidin-BF significantly inhibited pro-inflammatory factors secretion in human monocytic cells and P. acnes-induced O2.- production of human HaCaT keratinocyte cells. Observed by scanning electron microscopy, the surfaces of the treated pathogens underwent obvious morphological changes compared with the untreated controls, suggesting that this antimicrobial peptide exerts its action by disrupting membranes of microorganisms. The efficacy of cathelicidin-BF gel topical administering was evaluated in experimental mice skin colonization model. In vivo anti-inflammatory effects of cathelicidin-BF were confirmed by relieving P. acnes-induced mice ear swelling and granulomatous inflammation. The anti-inflammatory effects combined with potent antimicrobial activities and O2.- production inhibition activities of cathelicidin-BF indicate its potential as a novel therapeutic option for acne vulgaris.


Asunto(s)
Acné Vulgar/tratamiento farmacológico , Catelicidinas/uso terapéutico , Secuencia de Aminoácidos , Animales , Antiinflamatorios/farmacología , Catelicidinas/química , Catelicidinas/farmacología , Membrana Celular/efectos de los fármacos , Membrana Celular/ultraestructura , Recuento de Colonia Microbiana , Citocinas/biosíntesis , Oído/microbiología , Humanos , Cinética , Ratones , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Datos de Secuencia Molecular , Propionibacterium acnes/citología , Propionibacterium acnes/efectos de los fármacos , Propionibacterium acnes/crecimiento & desarrollo , Propionibacterium acnes/ultraestructura , Superóxidos/metabolismo
13.
PLoS One ; 6(3): e17519, 2011 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-21423730

RESUMEN

UNLABELLED: Direct-acting fibrin(ogen)olytic agents such as plasmin have been proved to contain effective and safety thrombolytic potential. Unfortunately, plasmin is ineffective when administered by the intravenous route because it was neutralized by plasma antiplasmin. Direct-acting fibrin(ogen)olytic agents with resistance against antiplasmin will brighten the prospect of anti-thrombosis. As reported in 'Compendium of Materia Medica', the insect of Eupolyphaga sinensis Walker has been used as traditional anti-thrombosis medicine without bleeding risk for several hundreds years. Currently, we have identified a fibrin(ogen)olytic protein (Eupolytin1) containing both fibrin(ogen)olytic and plasminogen-activating (PA) activities from the beetle, E. sinensis. OBJECTIVES: To investigate the role of native and recombinant eupolytin1 in fibrin(ogen)olytic and plasminogen-activating processes. METHODS AND RESULTS: Using thrombus animal model, eupolytin1 was proved to contain strong and rapid thrombolytic ability and safety in vivo, which are better than that of urokinase. Most importantly, no bleeding complications were appeared even the intravenous dose up to 0.12 µmol/kg body weight (3 times of tested dose which could completely lyse experimental thrombi) in rabbits. It is the first report of thrombolytic agents containing both direct-acting fibrin(ogen)olytic and plasminogen-activating activities. CONCLUSIONS: The study identified novel thrombolytic agent with prospecting clinical potential because of its bi-functional merits containing both plasmin- and PA-like activities and unique pharmacological kinetics in vivo.


Asunto(s)
Proteínas Antitrombina/metabolismo , Fibrinólisis , Activadores Plasminogénicos/metabolismo , Secuencia de Aminoácidos , Animales , Proteínas Antitrombina/administración & dosificación , Proteínas Antitrombina/química , Proteínas Antitrombina/aislamiento & purificación , Tiempo de Sangría , Escarabajos , Fibrinólisis/efectos de los fármacos , Tracto Gastrointestinal/metabolismo , Hemostasis/efectos de los fármacos , Humanos , Hidrólisis/efectos de los fármacos , Cinética , Ratones , Datos de Secuencia Molecular , Filogenia , Conejos , Activador de Plasminógeno de Tipo Uroquinasa/farmacología
14.
Adv Exp Med Biol ; 680: 497-511, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20865535

RESUMEN

Dressing the problem of virtual screening is a long-term goal in the drug discovery field, which if properly solved, can significantly shorten new drugs' R&D cycle. The scoring functionality that evaluates the fitness of the docking result is one of the major challenges in virtual screening. In general, scoring functionality in docking requires a large amount of floating-point calculations, which usually takes several weeks or even months to be finished. This time-consuming procedure is unacceptable, especially when highly fatal and infectious virus arises such as SARS and H1N1, which forces the scoring task to be done in a limited time. This paper presents how to leverage the computational power of GPU to accelerate Dock6's (http://dock.compbio.ucsf.edu/DOCK_6/) Amber (J. Comput. Chem. 25: 1157-1174, 2004) scoring with NVIDIA CUDA (NVIDIA Corporation Technical Staff, Compute Unified Device Architecture - Programming Guide, NVIDIA Corporation, 2008) (Compute Unified Device Architecture) platform. We also discuss many factors that will greatly influence the performance after porting the Amber scoring to GPU, including thread management, data transfer, and divergence hidden. Our experiments show that the GPU-accelerated Amber scoring achieves a 6.5× speedup with respect to the original version running on AMD dual-core CPU for the same problem size. This acceleration makes the Amber scoring more competitive and efficient for large-scale virtual screening problems.


Asunto(s)
Descubrimiento de Drogas/estadística & datos numéricos , Evaluación Preclínica de Medicamentos/estadística & datos numéricos , Interfaz Usuario-Computador , Algoritmos , Biología Computacional , Simulación por Computador , Humanos , Técnicas In Vitro , Ligandos , Simulación de Dinámica Molecular/estadística & datos numéricos , Programas Informáticos , Diseño de Software
15.
PLoS One ; 3(6): e2381, 2008 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-18584053

RESUMEN

BACKGROUND: Lectins are sugar-binding proteins that specifically recognize sugar complexes. Based on the specificity of protein-sugar interactions, different lectins could be used as carrier molecules to target drugs specifically to different cells which express different glycan arrays. In spite of lectin's interesting biological potential for drug targeting and delivery, a potential disadvantage of natural lectins may be large size molecules that results in immunogenicity and toxicity. Smaller peptides which can mimic the function of lectins are promising candidates for drug targeting. PRINCIPAL FINDINGS: Small peptide with lectin-like behavior was screened from amphibian skin secretions and its structure and function were studied by NMR, NMR-titration, SPR and mutant analysis. A lectin-like peptide named odorranalectin was identified from skin secretions of Odorrana grahami. It was composed of 17 aa with a sequence of YASPKCFRYPNGVLACT. L-fucose could specifically inhibit the haemagglutination induced by odorranalectin. (125)I-odorranalectin was stable in mice plasma. In experimental mouse models, odorranalectin was proved to mainly conjugate to liver, spleen and lung after i.v. administration. Odorranalectin showed extremely low toxicity and immunogenicity in mice. The small size and single disulfide bridge of odorranalectin make it easy to manipulate for developing as a drug targeting system. The cyclic peptide of odorranalectin disclosed by solution NMR study adopts a beta-turn conformation stabilized by one intramolecular disulfide bond between Cys6-Cys16 and three hydrogen bonds between Phe7-Ala15, Tyr9-Val13, Tyr9-Gly12. Residues K5, C6, F7, C16 and T17 consist of the binding site of L-fucose on odorranalectin determined by NMR titration and mutant analysis. The structure of odorranalectin in bound form is more stable than in free form. CONCLUSION: These findings identify the smallest lectin so far, and show the application potential of odorranalectin for drug delivery and targeting. It also disclosed a new strategy of amphibian anti-infection.


Asunto(s)
Anuros/metabolismo , Sistemas de Liberación de Medicamentos , Lectinas/metabolismo , Péptidos/metabolismo , Animales , Bacterias/metabolismo , Secuencia de Bases , Metabolismo de los Hidratos de Carbono , ADN Complementario/genética , Fucosa/metabolismo , Hemaglutinación , Radioisótopos de Yodo , Lectinas/administración & dosificación , Lectinas/química , Lectinas/farmacocinética , Espectroscopía de Resonancia Magnética , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Péptidos/administración & dosificación , Péptidos/química , Péptidos/farmacocinética , Piel/metabolismo , Soluciones , Factores de Tiempo , Distribución Tisular , Volumetría
16.
Eur J Med Chem ; 40(10): 972-6, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16006013

RESUMEN

A set of molecular properties (variables) of 24 ganoderic acids with cytotoxicities against Meth-A tumor cells was calculated by the molecular orbital semi-empirical method AM1 and ChemPropStd. Pattern recognition techniques, principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to reduce dimensionality and investigate which subset of variables could be more effective for classifying the ganoderic acids according to their degree of cytotoxicities against tumor cells. The PCA and HCA studies showed that EHOMO (highest occupied molecular orbital energy), Mulliken electronegativity (chi), electronic energy (Eel), log P (octanol/water partition coefficient), and Connolly molecular area (MA) are the most important variables for the classification between the ganoderic acids with higher and lower cytotoxicities against tumor cells.


Asunto(s)
Ácidos/química , Ácidos/toxicidad , Medicamentos Herbarios Chinos/química , Neoplasias/patología , Reishi/química , Ácidos/clasificación , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Análisis por Conglomerados , Ratones , Estructura Molecular , Reconocimiento de Normas Patrones Automatizadas , Fitoterapia , Análisis de Componente Principal , Relación Estructura-Actividad
17.
Zhongguo Zhong Yao Za Zhi ; 30(21): 1717-20, 2005 Nov.
Artículo en Chino | MEDLINE | ID: mdl-16400953

RESUMEN

The progress of Chinese medicine modernization is slow in china, and one of the reason is the dated process method. The fermentation technology of pharmaceutical fungi is more and more perfect. To process Chinese medicine by pharmaceutical fungi could enhance the effective density of active ingredient in Chinese medicine, and the fungi could produce a variety of active secondary metabolite, moreover, some compounds in Chinese medicine could be bio-transformed to produce new compound by pharmaceutical fungi in the fermentation. So process Chinese medicine by pharmaceutical fungi could produce de novo Chinese medicine preparations which include a variety of bioactive compounds, and it is suitable to produce in a large scale and convenient to control the quality. To process Chinese medicine by submerged fermentation of pharmaceutical fungi provides a new process method for Chinese medicine.


Asunto(s)
Medicamentos Herbarios Chinos/metabolismo , Hongos/metabolismo , Plantas Medicinales/metabolismo , Tecnología Farmacéutica/métodos , Biotransformación , Fermentación , Control de Calidad
18.
Wei Sheng Wu Xue Bao ; 43(4): 519-22, 2003 Aug.
Artículo en Chino | MEDLINE | ID: mdl-16276930

RESUMEN

Effects of water and ethanol extracts of 10 Chinese medicines, such as Astragalus membranaceus, Coix lachryma-jobi, etc., on biomass and exopolysaccharide of Ganoderma lucidum were studied by submerged culture. The results showed: water extracts of all medicines can improve the culture of G. lucidum except of A. membranaceus, ethanol extracts of C. lachryma-jobi, Dioscorea opposita, Codonopsis pilosula, and Achyranthes bidentata( < 187.5g Medicine/L substrate) can also increase the biomass of G. lucidum, but the ethanol extracts of Angelica sinensis, Dendrobium nobile check the growth of G. lucidum. The production of exopolysa-ccharide can be improved by all the Chinese medicines and their dosage used in this experiment, Although A. sinensis, D. Nobile check the growth of G. lucidum, they could stimulate the secretion of exopolysaccharide in lower dosage. It is concluded that some Chinese medicines, such as C. lachryma-jobi, D. opposita, C. pilosula, etc. can be processed by the fermentation of G. lucidum, and bio-active compound can be produced by adding appropriate Chinese medicine in the substrate to culture G. lucidum.


Asunto(s)
Técnicas de Cultivo/métodos , Medicamentos Herbarios Chinos/farmacología , Reishi/efectos de los fármacos , Biomasa , Medios de Cultivo/química , Medios de Cultivo/metabolismo , Medios de Cultivo/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/metabolismo , Fermentación/efectos de los fármacos , Polisacáridos/metabolismo , Reishi/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA