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1.
Toxicol Sci ; 196(2): 152-169, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-37702017

RESUMEN

The FDA Modernization Act 2.0 has brought nonclinical drug evaluation into a new era. In vitro models are widely used and play an important role in modern drug development and evaluation, including early candidate drug screening and preclinical drug efficacy and toxicity assessment. Driven by regulatory steering and facilitated by well-defined physiology, novel in vitro skin models are emerging rapidly, becoming the most advanced area in alternative testing research. The revolutionary technologies bring us many in vitro skin models, either laboratory-developed or commercially available, which were all built to emulate the structure of the natural skin to recapitulate the skin's physiological function and particular skin pathology. During the model development, how to achieve balance among complexity, accessibility, capability, and cost-effectiveness remains the core challenge for researchers. This review attempts to introduce the existing in vitro skin models, align them on different dimensions, such as structural complexity, functional maturity, and screening throughput, and provide an update on their current application in various scenarios within the scope of chemical testing and drug development, including testing in genotoxicity, phototoxicity, skin sensitization, corrosion/irritation. Overall, the review will summarize a general strategy for in vitro skin model to enhance future model invention, application, and translation in drug development and evaluation.


Asunto(s)
Dermatitis Fototóxica , Piel , Animales , Evaluación Preclínica de Medicamentos/métodos , Irritantes , Alternativas a las Pruebas en Animales
2.
Acta Pharmacol Sin ; 43(8): 2016-2025, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35022542

RESUMEN

Macrophages play a critical role in the pathogenesis of acetaminophen (APAP)-induced liver injury (AILI), a major cause of acute liver failure or even death. Sapidolide A (SA) is a sesquiterpene lactone extracted from Baccaurea ramiflora Lour., a folk medicine used in China to treat inflammatory diseases. In this study, we investigated whether SA exerted protective effects on macrophages, thus alleviated the secondary hepatocyte damage in an AILI. We showed that SA (5-20 µM) suppressed the phosphorylated activation of NF-κB in a dose-dependent manner, thereby inhibiting the expression and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in LPS/ATP-treated mouse bone marrow-derived primary macrophages (BMDMs). In human hepatic cell line L02 co-cultured with BMDMs, SA (10 µM) protected macrophages from the pyroptosis induced by APAP-damaged L02 cells. Moreover, SA treatment reduced the secondary liver cell damage aggravated by the conditioned medium (CM) taken from LPS/ATP-treated macrophages. The in vivo assessments conducted on mice pretreated with SA (25, 50 mg/kg, ip) then with a single dose of APAP (400 mg/kg, ip) showed that SA significantly alleviated inflammatory responses of AILI by inhibiting the expression and activation of the NLRP3 inflammasome. In general, the results reported herein revealed that SA exerts anti-inflammatory effects by regulating NLRP3 inflammasome activation in macrophages, which suggests that SA has great a potential for use in the treatment of AILI patients.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Acetaminofén , Adenosina Trifosfato/metabolismo , Animales , Humanos , Inflamasomas/metabolismo , Lipopolisacáridos/farmacología , Hígado/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR/metabolismo
3.
Front Pharmacol ; 12: 721156, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34658860

RESUMEN

Stroke is the third most common disease all over the world, which is regarded as a hotspot in medical research because of its high mortality and morbidity. Stroke, especially ischemic stroke, causes severe neural cell death, and no effective therapy is currently available for neuroregeneration after stroke. Although many therapies have been shown to be effective in preclinical studies of ischemic stroke, almost none of them passed clinical trials, and the reasons for most failures have not been well identified. In this review, we focus on several novel methods, such as traditional Chinese medicine, stem cell therapy, and exosomes that have not been used for ischemic stroke till recent decades. We summarize the proposed basic mechanisms underlying these therapies and related clinical results, discussing advantages and current limitations for each therapy emphatically. Based on the limitations such as side effects, narrow therapeutic window, and less accumulation at the injury region, structure transformation and drug combination are subsequently applied, providing a deep understanding to develop effective treatment strategies for ischemic stroke in the near future.

4.
Compr Rev Food Sci Food Saf ; 20(2): 2015-2039, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33594822

RESUMEN

Pectic substances, one of the cell wall polysaccharides, exist widespread in vegetables and fruits. A surge of recent research has revealed that pectic substances can inhibit gut inflammation and relieve inflammatory bowel disease symptoms. However, physiological functions of pectins are strongly structure dependent. Pectic substances are essentially heteropolysaccharides composed of homogalacturonan and rhamnogalacturonan backbones substituted by various neutral sugar sidechains. Subtle changes in the architecture of pectic substances may remarkably influence the nutritional function of gut microbiota and the host homeostasis of immune system. In this context, developing a structure-function understanding of how pectic substances have an impact on an inflammatory bowel is of primary importance for diet therapy and new drugs. Therefore, the present review has summarized the polycomponent nature of pectic substances, the activities of different pectic polymers, the effects of molecular characteristics and the underlying mechanisms of pectic substances. The immunomodulated property of pectic substances depends on not only the chemical composition but also the physical structure characteristics, such as molecular weight (Mw ) and chain conformation. The potential mechanisms by which pectic substances exert their protective effects are mainly reversing the disordered gut microbiota, regulating immune cells, enhancing barrier function, and inhibiting pathogen adhesion. The manipulation of pectic substances on gut health is sophisticated, and the link between structural specificity of pectins and selective regulation needs further exploration.


Asunto(s)
Frutas , Pectinas , Pared Celular , Polisacáridos , Verduras
5.
Phytother Res ; 35(5): 2785-2796, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33462870

RESUMEN

Drug-induced liver injury (DILI) has become a significant health care problem worldwide. Centella asiatica (L.) urban was traditionally used to prevent or treat various diseases, yet whether it works on hepatic injury remains unclear. In this study, multiple experimental models with different damage degrees and types of liver injury have been established to evaluate the hepatoprotective effects of an n-butanol extract of Centella asiatica (CA-BU). Our results revealed that CA-BU improved hepatocyte L02 cells survival from H2 O2 -induced oxidative damage in a concentration-dependent manner. We further verified the hepatoprotective effects of CA-BU in mice models of acetaminophen-induced acute liver injury (one of the most common DILIs clinically) and CCl4 -induced acute chemical liver injury, and a rat model of chronic alcoholic steatohepatitis. Furthermore, network pharmacology approaches were performed to explore the underlying mechanisms, and we predicted AKT1, EGFR, VEGFA, and STAT3 as the potential therapeutic targets. In follow-up studies, we will focus on targets verification and provide a deeper insight into the mechanisms of CA-BU against liver damage. Finally, we hope that these findings will provide new ideas and insights for the treatment of acute or chronic liver injury in the clinic.

6.
Carbohydr Polym ; 245: 116526, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32718630

RESUMEN

Rhamnogalacturonan I (RG-I) pectin are regarded as strong galectin-3 (Gal-3) antagonist because of galactan sidechains. The present study focused on discussing the effects of more structural regions in pectin on the anti-Gal-3 activity. The water-soluble pectin (WSP) recovered from citrus canning processing water was categorized as RG-I pectin. The controlled enzymatic hydrolysis was employed to sequentially remove the α-1,5-arabinan, homogalaturonan and ß-1,4-galactan in WSP. The Gal-3-binding affinity KD (kd/ka) of WSP and debranched pectins were calculated to be 0.32 µM, 0.48 µM, 0.56 µM and 1.93 µM. Moreover, based on the more sensitive cell line (MCF-7) model, the IC30 value of WSP was lower than these of modified pectins, indicating decreased anti-Gal-3 activity. Our results suggested that the total amount of neutral sugar sidechains, the length of arabinan and cooperation between HG and RG-I played important roles in the anti-Gal-3 activity of WSP, not the Gal/Ara ratio or RG-I/HG ratio. These results provided a new insight into structure-activity relationship of citrus segment membrane RG-I as a galectin-3 antagonist and a new functional food.


Asunto(s)
Proteínas Sanguíneas/antagonistas & inhibidores , Membrana Celular/química , Citrus/química , Galactanos/farmacología , Galectinas/antagonistas & inhibidores , Pectinas/química , Pectinas/farmacología , Proteínas Sanguíneas/metabolismo , Pared Celular/química , Frutas/química , Galectinas/metabolismo , Humanos , Hidrólisis , Células MCF-7 , Pectinas/metabolismo , Células Vegetales , Polisacáridos/química , Unión Proteica , Solubilidad , Relación Estructura-Actividad , Agua/química
7.
Acta Biomater ; 50: 534-545, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28027959

RESUMEN

Gold nanorods (AuNRs) are suitable candidates for photothermal therapy in vivo, because of their excellent ability to transfer near-infrared (NIR) light into heat. However, appropriate surface should be generated on AuNRs before their in vivo application because of the low colloidal stability in complicate biological environment and relatively strong toxicity compared to their pristine stabilizer cetyltrimethylammonium bromide. In the current study, polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, was used to stabilize AuNRs due to its excellent hydrophilicity and biocompatibility. Polysarcosine with optimized molecular weight was synthesized and used to modify AuNRs by traditional ligand exchange. The grafting of PS on AuNRs was evidenced by fourier transform infrared (FTIR) spectroscopy and the alternation of surface zeta potential. The polysarcosine coated AuNRs (Au@PS) showed good stabilities in wide pH range and simulated physiological buffer with the ligand competition of dithiothreitol (DTT). The Au@PS NRs had neglectable cytotoxicity and showed efficient ablation of tumor cells in vitro. Moreover, Au@PS NRs had a longer circulation time in body that resulted in a higher accumulation in solid tumors after intravenous injection, compared to AuNRs capped with polyethylene glycol (PEG). Photothermal therapy in vivo demonstrated that the tumors were completely destroyed by single-time irradiation of NIR laser after one-time injection of the polysarcosine capped AuNRs. The Au@PS NRs did not cause obvious toxicity in vivo, suggesting promising potential in cancer therapy. STATEMENT OF SIGNIFICANCE: In current study, polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, was used to stabilize AuNRs due to its excellent hydrophilicity and biocompatibility. The polysarcosine coated AuNRs (Au@PS) showed good stabilities in wide pH range and simulated physiological buffer. The Au@PS NRs had very low cytotoxicity and showed high efficacy for the ablation of cancer cells in vitro. Moreover, Au@PS NRs had a longer circulation time in blood that led to a higher accumulation in tumors after intravenous injection, compared to AuNRs capped with polyethylene glycol (PEG). In vivo photothermal therapy showed that tumors were completely cured without reoccurrence by one-time irradiation of NIR laser after a single injection of the polysarcosine modified AuNRs.


Asunto(s)
Oro/química , Hipertermia Inducida , Nanotubos/química , Neoplasias/terapia , Péptidos/química , Fototerapia , Sarcosina/análogos & derivados , Células A549 , Animales , Materiales Biocompatibles/farmacología , Circulación Sanguínea , Supervivencia Celular , Coloides/química , Ligandos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Fluorescente , Nanotubos/ultraestructura , Neoplasias/patología , Sarcosina/química , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Espectroscopía Infrarroja Corta , Distribución Tisular , Carga Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Cancer Lett ; 342(1): 82-91, 2014 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-24001610

RESUMEN

Enormous efforts have been made to explore small molecules that interfere with the TGF-ß signaling pathway, so as to inhibit EMT and the cancer metastasis, but few agents have been identified. In this study, we demonstrated that Nutlin-3 could abolish the down-regulation of E-cadherin induced by TGF-ß1 in p53-deficient cancer cells. Further studies revealed that Nutlin-3 prohibited EMT by blocking the phosphorylation of Smad2/3, resulting in the decreased transcription of Snail/Slug. In addition, Nutlin-3 suppressed the motility of cancer cells, and potentiated the anti-proliferative activity of gefitinib and lapatinib. Collectively, Nutlin-3 could inhibit EMT and enhance the anti-cancer activity of EGFR inhibitors by interfering with the canonical TGF-ß1-Smad-Snail/Slug axis, in a p53-independent manner.


Asunto(s)
Antineoplásicos/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Imidazoles/farmacología , Piperazinas/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/fisiología , Antígenos CD , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Receptores ErbB/antagonistas & inhibidores , Gefitinib , Expresión Génica/efectos de los fármacos , Humanos , Lapatinib , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Procesamiento Proteico-Postraduccional , Quinazolinas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Smad/metabolismo , Factores de Transcripción de la Familia Snail , Factores de Transcripción/metabolismo , Regulación hacia Arriba
9.
Nat Prod Commun ; 7(8): 971-2, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22978206

RESUMEN

A new sesquiterpenoid, 1alpha,5alpha-epoxy-4alpha-hydroxyl-4beta,10beta-dimethyl-7alphaH,10alphaH-guaia-l1(13)-en-12-oic acid (1), and four known compounds, lactucin (2), 1beta-hydroxy-7alphaH,8,11betaH-eudesm-3-en-8,12-olide (3), 13,14-seco-stigma 9(11),14(15)-dien-3alpha-ol (4), and bacosterol-3-O-beta-D-glucopyranoside (5) were isolated from Cichorium intybus L. Their structures were determined on the basis of detailed analysis of their 1D- and 2D-NMR spectroscopic and mass spectrometric data. Compounds 2 and 4 showed strong activities against the A2780 cell line with IC50 values of 1.81 and 0.07 microM, respectively.


Asunto(s)
Cichorium intybus/química , Terpenos/química , Datos de Secuencia Molecular
10.
Bioorg Med Chem ; 20(9): 2837-44, 2012 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-22480851

RESUMEN

A series of novel 2-aliphatic cyclic amine-3-(arylsulfonyl)quinoxalines was synthesized based on the structural features of a previously identified lead, WR1. The 2-piperidinol-3-(arylsulfonyl)quinoxalines, which showed excellent antitumor activities against five human cell lines, with inhibitory activities ranging from 0.34 to 2.32 µM, proved to be a promising class of novel PI3Kα inhibitors. The most potent compound 10d (WR23) showed an inhibitory IC(50) value of 0.025µM against PI3Kα and significant pAkt suppression effect. Molecular docking analysis was performed to determine possible binding modes between PI3Kα and target compounds.


Asunto(s)
Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Piperidinas/química , Piperidinas/farmacología , Quinoxalinas/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Sitios de Unión , Dominio Catalítico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Simulación por Computador , Evaluación Preclínica de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quinoxalinas/síntesis química , Quinoxalinas/farmacología , Relación Estructura-Actividad
11.
Invest New Drugs ; 30(1): 37-47, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20686816

RESUMEN

Unlike its cytotoxicity in p53-functional cell lines, Nutlin-1, the small-molecule inhibitor of murine double minute (MDM2), significantly enhanced the differentiation-inducing activity of all-trans retinoic acid (ATRA) in HL60 and NB4 cells (p53-nonfunctional) but not in U937 cells (p53 wild-type). Moreover, we demonstrated that the synergistic differentiation-inducing activity of Nutlin-1 combined with ATRA appeared in a p53-independent manner. In the present study, we found that ATRA could selectively induce expression of p-glycoprotein (p-gp) in HL60 and NB4 cells but not in U937 cells. Investigation of p-gp-ATPase activity showed that Nutlin-1 and ATRA were likely to act as p-gp transport substrates. Furthermore, Nutlin-1 enhanced the ability of ATRA to induce expression of the myeloid differentiation-related transcription factor C/EBPß and to reduce expression of c-myc. Additionally, the expression of retinoic acid receptor α (RARα) was further reduced in cells treated with ATRA in combination with Nutlin-1. Taken together, the mechanisms of synergistic differentiation-inducing activity of Nutlin-1 combined with ATRA could be attributed to Nutlin-1 competitive binding to p-gp, leading to ATRA efflux inhibition, and then the differentiation pathways involved were therefore further activated. Nutlin-1 might be a useful adjuvant with ATRA for patients with retinoid-resistant leukemia induced by overexpression of p-gp.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Leucemia Mieloide/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Unión Competitiva , Transporte Biológico , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Células HL-60 , Humanos , Imidazoles/metabolismo , Imidazoles/farmacología , Leucemia Mieloide/genética , Leucemia Mieloide/patología , Piperazinas/metabolismo , Piperazinas/farmacología , Proteínas Proto-Oncogénicas c-mdm2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Interferencia de ARN , Receptores de Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Factores de Tiempo , Transfección , Tretinoina/metabolismo , Tretinoina/farmacología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Células U937 , Verapamilo/farmacología
12.
Eur J Med Chem ; 46(11): 5540-8, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21945250

RESUMEN

A series of novel 2-arylamino-3-(arylsulfonyl)quinoxalines was synthesized through a newly developed approach. All synthesized target compounds were screened for their cytotoxicities against cancer cell lines including PC3, A549, HCT116, HL60 and KB. Representative compounds with favorable cytotoxicities were tested for their PI3Kα inhibitory activities. Among the synthesized target compounds, 17 (PI3Kα IC(50): 0.07 µM) displayed the most potent cellular activities (IC(50) values of 0.14 µM, 0.07 µM, 0.95 µM and 0.05 µM against PC3, A549, HCT116 and HL 60, respectively).


Asunto(s)
Técnicas de Química Sintética , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Quinoxalinas/síntesis química , Quinoxalinas/farmacología , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase Ia/química , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Humanos , Concentración 50 Inhibidora , Modelos Moleculares , Conformación Proteica , Quinoxalinas/química , Relación Estructura-Actividad
13.
J Pharmacol Exp Ther ; 334(2): 489-99, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20472666

RESUMEN

Malignant tumors remain a significant health threat, with death often occurring as a result of metastasis. Cell adhesion is a crucial step in the metastatic cascade of tumor cells, and interruption of this step is considered to be a logical strategy for prevention and treatment of tumor metastasis. Celastrol [3-hydroxy-24-nor-2-oxo-1(10),3,5,7-friedelatetraen-29-oic acid], a quinone methide triterpene from the medicinal plant Tripterygium wilfordii, possesses antitumor activities, whereas the underlying mechanism(s) remains elusive. Here, we found that celastrol inhibited cell-extracellular matrix (ECM) adhesion of human lung cancer 95-D and mouse melanoma B16F10 cells. This inhibition was achieved through suppressing beta1 integrin ligand affinity and focal adhesion formation, accompanied by the reduced phosphorylation of focal adhesion kinase (FAK). In understanding the underlying mechanisms, we found that celastrol activated p38 mitogen-activated protein kinase (MAPK) by phosphorylation before the decrement of phosphorylated FAK and that this action was independent of the presence of fibronectin. Using 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), a specific inhibitor of p38 MAPK, the effects of celastrol on beta1 integrin function, cell-ECM adhesion, and phosphorylation of FAK were partially attenuated. In addition, focal adhesion-dependent cell migration and invasion were both inhibited by treatment with celastrol. Finally, the antimetastatic activity of celastrol was examined in vivo using the B16F10-green fluorescent protein-injected C57BL/6 mouse model, as indicated by decreased pulmonary metastases in celastrol-administrated mice. Taken together, these data demonstrate for the first time that celastrol exerts potent antimetastatic activity both in vitro and in vivo, and they provide new evidence for the critical roles of p38 MAPK in the regulation of integrin function and cell adhesion.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Matriz Extracelular/fisiología , Integrina beta1/fisiología , Metástasis de la Neoplasia/tratamiento farmacológico , Proteínas Quinasas p38 Activadas por Mitógenos/fisiología , Animales , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Activación Enzimática , Fibronectinas/fisiología , Humanos , Ratones , Ratones Endogámicos C57BL , Invasividad Neoplásica , Metástasis de la Neoplasia/patología , Proteínas Proto-Oncogénicas c-akt/fisiología , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores
14.
J Ethnopharmacol ; 128(1): 154-9, 2010 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-20051258

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The radix of Acorus calamus L. (AC) is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia, and we previously reported the insulin sensitizing activity of the ethyl acetate fraction of AC (ACE). AIM OF THE STUDY: To investigate the insulin releasing and alpha-glucosidase inhibitory activity of ACE in vitro and in vivo. MATERIALS AND METHODS: Insulin releasing and alpha-glucosidase inhibitory effects of different fractions from AC were detected in vitro using HIT-T15 cell line and alpha-glucosidase enzyme. Furthermore, effects of ACE orally on serum glucose were detected in fasted and glucose/amylum challenged normal mice. RESULTS: AC and ACE increased insulin secretion in HIT-T15 cells as gliclazide did. As in vivo results, ACE (400 and 800 mg/kg) significantly decreased fasting serum glucose, and suppressed the increase of blood glucose levels after 2g/kg glucose loading in normal mice. In addition, ACE as a mixed-type inhibitor inhibited alpha-glucosidase activity in vitro with an IC(50) of 0.41 microg/ml, and 100mg/kg of it clearly reduced the increase of blood glucose levels after 5 g/kg amylum loading in normal mice. CONCLUSIONS: Apart from its insulin sensitizing effect, ACE may have hypoglycemic effects via mechanisms of insulin releasing and alpha-glucosidase inhibition, and thus improves postprandial hyperglycemia and cardiovascular complications.


Asunto(s)
Acetatos/química , Acorus/química , Inhibidores Enzimáticos/farmacología , Inhibidores de Glicósido Hidrolasas , Insulina/metabolismo , Animales , Glucemia/análisis , Línea Celular , Técnicas In Vitro , Secreción de Insulina , Cinética , Masculino , Ratones , Ratones Endogámicos ICR , Periodo Posprandial
15.
J Ethnopharmacol ; 123(2): 288-92, 2009 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-19429374

RESUMEN

UNLABELLED: Acorus calamus L. (AC), family Araceae, have been used in the Indian and Chinese systems of medicine for hundreds of years. The radix of AC is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia. AIM OF THE STUDY: To investigate the insulin sensitizing activity and antidiabetic effects of the ethyl acetate fraction of AC (ACE). MATERIALS AND METHODS: Glucose consumption mediated by insulin was detected in L6 rat skeletal muscle cells. Diabetes and its complications related indexes were monitored after orally administrating to genetically obese diabetic C57BL/Ks db/db mice daily for 3 weeks. RESULTS: ACE (12.5 and 25 microg/ml) increased glucose consumption mediated by insulin in L6 cells (p<0.05 and p<0.01). In db/db mice, ACE (100 mg/kg) significantly reduced serum glucose, triglyceride, reinforce the decrease of total cholesterol caused by rosiglitazone (at least p<0.05), and markedly reduced free fatty acid (FFA) levels and increased adiponectin levels (p<0.01 and p<0.05) as rosiglitazone did (p<0.05 and p<0.001). Serum insulin was decreased but not significantly. In addition, ACE decreased the intake of food and water, and did not increase body weight gain whereas rosiglitazone did. CONCLUSIONS: Owing to the ability of insulin sensitizing, ACE has the potential to be useful for the treatment of diabetes and cardiovascular complications without body weight gain.


Asunto(s)
Acorus/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Extractos Vegetales/administración & dosificación , Acetatos/química , Administración Oral , Animales , Diabetes Mellitus Experimental/complicaciones , Glucosa/metabolismo , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/aislamiento & purificación , Insulina/sangre , Insulina/metabolismo , Resistencia a la Insulina , Masculino , Medicina Tradicional , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Extractos Vegetales/efectos adversos , Rosiglitazona , Tiazolidinedionas/efectos adversos , Tiazolidinedionas/farmacología , Aumento de Peso/efectos de los fármacos
16.
Zhongguo Zhong Yao Za Zhi ; 32(8): 722-5, 2007 Apr.
Artículo en Chino | MEDLINE | ID: mdl-17608230

RESUMEN

OBJECTIVE: To study galactagogue effect of Maidang Rutong granule on the lactation rats. METHOD: The experiments were designed to observe the efficiency of Maidang Rutong granule on lactescence, serum prolactin, and morphology of mammary gland with rat galactozemia model established by injecting l-dopa. RESULT: Maidang Rutong granule showed significant enhancement for lactescence and the offspring's body weight. It could antagonize the decrease of serum prolactin and the atrophy of mammary gland induced by l-dopa. CONCLUSION: Maidang Rutong granule exhibited significant galactagogue effect on the l-dopa-induced galactozemia in rats.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Trastornos de la Lactancia/fisiopatología , Glándulas Mamarias Animales/efectos de los fármacos , Animales , Animales Recién Nacidos , Atrofia , Peso Corporal/efectos de los fármacos , Combinación de Medicamentos , Femenino , Lactancia/efectos de los fármacos , Trastornos de la Lactancia/sangre , Trastornos de la Lactancia/inducido químicamente , Levodopa , Masculino , Glándulas Mamarias Animales/patología , Prolactina/sangre , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
17.
Phytother Res ; 21(6): 562-4, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17335118

RESUMEN

The effects of fractions partitioned from the ethanol extract of Acorus calamus L. (AC) on adipocyte differentiation were investigated using cultured mouse 3T3-L1 preadipocytes. The degree of differentiation was evaluated by measuring the cellular triglycerides and protein expression of the glucose transporter GLUT4 in 3T3-L1 cells. The ethyl acetate fraction of the AC extract (ACE) was found to enhance adipocyte differentiation as did rosiglitazone. The results of further fractionation of ACE indicated that the active fraction does not consist of beta-asarone, which is a toxic component of this plant. This finding suggests that ACE has potential insulin-sensitizing activity like rosiglitazone, and may improve type 2 diabetes.


Asunto(s)
Acorus/química , Adipocitos/efectos de los fármacos , Anisoles/química , Diferenciación Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Células 3T3-L1 , Acetatos/química , Adipocitos/citología , Adipocitos/metabolismo , Derivados de Alilbenceno , Animales , Relación Dosis-Respuesta a Droga , Transportador de Glucosa de Tipo 4/metabolismo , Ratones , Estructura Molecular , Extractos Vegetales/química , Rosiglitazona , Tiazolidinedionas/farmacología , Triglicéridos/metabolismo
18.
Zhong Yao Cai ; 26(12): 878-80, 2003 Dec.
Artículo en Chino | MEDLINE | ID: mdl-15058209

RESUMEN

OBJECTIVE: To study the protective effect and mechanism of total flavone from Elsholtzia blanda (TFEB) on Xiongbi symptom induced by coronary artery ligation in rats. METHODS: The left anterior descending coronary artery (LAD) of male rat was ligated for 3 h after feeding TFEB or 0.5% CMC for 5 d by ig. Then, the rats were decollated and the left ventricle were dyed by nitrotetrazolum blue chloride(NBT) to distinguish infraction area from non-infraction area. Myocardial infarction index was calculated accordingly to assess the effect of TFEB on myocardial ischemia. A piece of ventricular muscle come from apex of heart was dyed by hematoxylin and eosin (HE) to observe the degree of myocardial lesions by microscopic examination. Nitric oxide (NO) level in serum was measured to demonstrate the relevant mechanism. RESULTS: TFEB could markedly reduce the myocardial infraction index in a dose-dependent fashion (P < 0.05-0.01). Microscopic examination showed that the myocardium of sham group had no lesion in morphology and the muscle fiber kept integrity and the cardiac myocyte lined up in order. While control group displayed extensive swelling, rupture, confluent, even break in cardiac myocyte. TFEB could relieve the lesion degree of myocardium. NO level in serum after LAD ligation in TFEB 100 and 150 mg/kg groups was markedly reduced(P < 0.05-0.01). CONCLUSION: TFEB has protective effect on myocardial ischemia induced by LAD ligation in rats and can prevent against Xiongbi symptom, possibly via the decrease of NO level in serum.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Flavonoides/farmacología , Lamiaceae/química , Infarto del Miocardio/patología , Óxido Nítrico/sangre , Animales , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Flavonoides/administración & dosificación , Masculino , Isquemia Miocárdica/patología , Miocardio/patología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Plantas Medicinales/química , Ratas , Ratas Sprague-Dawley
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