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1.
Carbohydr Polym ; 211: 100-108, 2019 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-30824068

RESUMEN

Dried fruits of Terminalia chebula (TF) are used as herbal medicine for diverse symptoms, and their bioactivities are known to involve antioxidant activities. The aim of this study was to elucidate the structure and antioxidant effects of an active TF polysaccharide (TFP). The neutral polysaccharide (named as TFP-a) isolated by ion-exchange chromatography was a homogenous α-Glc-rich polysaccharide (over 70% α-Glc, 534.9 kDa, PDI 1.36) with a porous and flake-like morphology. Linkage and NMR data comprehensively showed that TFP-a was an amylopectin-type polysaccharide with (1→4)-α-Glc(p) backbone branched at C6/C2. Side chains were composed of (1→4)-ß-Gal(p) substituted with α-Ara(f), ß-GalUA(p), ß-GalUA(p)-Me, and α-Rham(p). In antioxidant activity assays, TFP-a exhibited potent and concentration-dependent antioxidant effects, including DPPH and superoxide radical scavenging and reducing power. We concluded that TFP-a is an amylopectin-type polysaccharide that may be used as a potential natural antioxidant.


Asunto(s)
Amilopectina/química , Antioxidantes/química , Frutas/química , Terminalia/química , Amilopectina/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Compuestos de Bifenilo/química , Estructura Molecular , Picratos/química , Superóxidos/química
2.
J Nanobiotechnology ; 17(1): 19, 2019 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-30696428

RESUMEN

BACKGROUND: Protein-based Cas9 in vivo gene editing therapeutics have practical limitations owing to their instability and low efficacy. To overcome these obstacles and improve stability, we designed a nanocarrier primarily consisting of lecithin that can efficiently target liver disease and encapsulate complexes of Cas9 with a single-stranded guide RNA (sgRNA) ribonucleoprotein (Cas9-RNP) through polymer fusion self-assembly. RESULTS: In this study, we optimized an sgRNA sequence specifically for dipeptidyl peptidase-4 gene (DPP-4) to modulate the function of glucagon-like peptide 1. We then injected our nanocarrier Cas9-RNP complexes directly into type 2 diabetes mellitus (T2DM) db/db mice, which disrupted the expression of DPP-4 gene in T2DM mice with remarkable efficacy. The decline in DPP-4 enzyme activity was also accompanied by normalized blood glucose levels, insulin response, and reduced liver and kidney damage. These outcomes were found to be similar to those of sitagliptin, the current chemical DPP-4 inhibition therapy drug which requires recurrent doses. CONCLUSIONS: Our results demonstrate that a nano-liposomal carrier system with therapeutic Cas9-RNP has great potential as a platform to improve genomic editing therapies for human liver diseases.


Asunto(s)
Sistemas CRISPR-Cas , Diabetes Mellitus Tipo 2/terapia , Dipeptidil Peptidasa 4/genética , Sistemas de Liberación de Medicamentos , Terapia Genética/métodos , Lecitinas , Liposomas , Animales , Glucemia/efectos de los fármacos , Línea Celular , Dipeptidil Peptidasa 4/metabolismo , Edición Génica , Marcación de Gen , Péptido 1 Similar al Glucagón/sangre , Humanos , Lecitinas/administración & dosificación , Lecitinas/química , Liposomas/administración & dosificación , Liposomas/química , Ratones , Ratones Noqueados , ARN Guía de Kinetoplastida/administración & dosificación , ARN Guía de Kinetoplastida/química , ARN Guía de Kinetoplastida/genética
3.
Bioorg Med Chem Lett ; 27(14): 3144-3147, 2017 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-28532669

RESUMEN

Two new pterosin glycosides, (2S,3S)-pterosin C 3-O-ß-d-(4'-(E)-caffeoyl)-glucopyranoside (1) and (2S,3S)-pterosin C 3-O-ß-d-(6'-(E)-p-coumaroyl)-glucopyranoside (2), were isolated from Pteris multifida (Pteridaceae) roots along with ten known pterosin compounds (3-12). The chemical structures of the isolated compounds were elucidated by extensive analysis of the 1D, 2D NMR, HRESIMS, and CD spectroscopic data. The cytotoxicities of 1-12 against HCT116 human colorectal cancer cell line were evaluated. Among the isolates, compound 1 showed moderate antiproliferative activity in HCT116 cells with an IC50 value of 8.0±1.7µM. Additionally, 1 induced the upregulation of the caspase-9 and procaspase-9 levels in Western blots and increased the annexin V/propidium iodide (PI)-positive cell population in flow cytometry.


Asunto(s)
Indanos/química , Indanos/farmacología , Pteris/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/toxicidad , Caspasa 9/metabolismo , Proliferación Celular/efectos de los fármacos , Dicroismo Circular , Neoplasias del Colon , Células HCT116 , Humanos , Indanos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Conformación Molecular , Extractos Vegetales/química , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Pteris/metabolismo , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/toxicidad
4.
Biomol Ther (Seoul) ; 22(6): 491-6, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25489415

RESUMEN

Photobiomodulation utilizes monochromatic (or quasimonochromatic) light in the electromagnetic region of 600∼1000 nm for the treatment of soft tissues in a nondestructive and nonthermal mode. It is conceivable that photobiomodulation is based upon the ability of the light to alter cell metabolism as it is absorbed by general hemoproteins and cytochrome c oxidase (COX) in particular. Recently it has been suggested radiation of visible and infrared (IR) activates retrograde signaling pathway from mitochondria to nucleus. In this review, the role of COX in the photobiomodulation will be discussed. Further a possible role of water as a photoreceptor will be suggested.

5.
Food Chem Toxicol ; 74: 156-63, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25301235

RESUMEN

Alzheimer's disease (AD) is closely associated with amyloid ß (Aß)-induced neurotoxicity and oxidative stress in the brain. Betula platyphylla, which has been used to treat various oxidative-stressed related diseases, has recently received attention for its preventive activity on age-related neurodegenerative diseases. In this study, we attempted to investigate the effects of B. platyphylla bark (BPB-316) on Aß(1-42)-induced neurotoxicity and memory impairment. Oral treatment using BPB-316 significantly attenuated Aß-induced memory impairment which was evaluated by behavioral tests including the passive avoidance, Y-maze and Morris water maze test. BPB-316 also inhibited the elevation of ß-secretase activity accompanying the reduced Aß(1-42) levels in the hippocampus of the brain. Furthermore, BPB-316 significantly decreased the acetylcholinesterase activity and increased the glutathione content in the hippocampus. In addition, we confirmed that the expression of both cAMP responsive element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus of Aß(1-42)-injected mice were markedly upregulated by the treatment of BPB-316. Our data suggest that the extracts of B. platyphylla bark might be a potential therapeutic agent against AD.


Asunto(s)
Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/toxicidad , Betula/química , Discapacidades para el Aprendizaje/inducido químicamente , Discapacidades para el Aprendizaje/prevención & control , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/prevención & control , Fragmentos de Péptidos/antagonistas & inhibidores , Fragmentos de Péptidos/toxicidad , Extractos Vegetales/farmacología , Acetilcolinesterasa/metabolismo , Secretasas de la Proteína Precursora del Amiloide/biosíntesis , Secretasas de la Proteína Precursora del Amiloide/genética , Animales , Ácido Aspártico Endopeptidasas/biosíntesis , Ácido Aspártico Endopeptidasas/genética , Reacción de Prevención/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Glutatión/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Discapacidades para el Aprendizaje/psicología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/psicología , Ratones , Ratones Endogámicos ICR , Corteza de la Planta/química
6.
Molecules ; 18(9): 10484-96, 2013 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-23999723

RESUMEN

Obesity is reported to be associated with excessive growth of adipocyte mass tissue as a result of increases in the number and size of adipocytes differentiated from preadipocytes. To search for anti-adipogenic phytochemicals, we screened for inhibitory activities of various plant sources on adipocyte differentiation in 3T3-L1 preadipocytes. Among the sources, a methanolic extract of Salix pseudo-lasiogyne twigs (Salicaceae) reduced lipid accumulation in a concentration-dependent manner. During our search for anti-adipogenic constituents from S. pseudo-lasiogyne, five salicortin derivatives isolated from an EtOAc fraction of this plant and bearing 1-hydroxy-6-oxo-2-cyclohexene-carboxylate moieties, namely 2',6'-O-acetylsalicortin (1), 2'-O-acetylsalicortin (2), 3'-O-acetylsalicortin (3), 6'-O-acetylsalicortin (4), and salicortin (5), were found to significantly inhibit adipocyte differentiation in 3T3-L1 cells. In particular, 2',6'-O-acetylsalicortin (1) had the most potent inhibitory activity on adipocyte differentiation, with an IC50 value of 11.6 µM, and it significantly down-regulated the expressions of CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element binding protein 1 (SREBP1c). Furthermore, 2',6'-O-acetylsalicortin (1) suppressed mRNA expression levels of C/EBPß during the early stage of adipocyte differentiation and stearoyl coenzyme A desaturase 1 (SCD-1), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) expression, target genes of SREBP1c. In the present study, we demonstrate that the anti-adipogenesis mechanism of 2',6'-O-acetylsalicortin (1) may be mediated via down-regulation of C/EBPα and SREBP1c dependent pathways. Through their anti-adipogenic activity, salicortin derivatives may be potential novel therapeutic agents against obesity.


Asunto(s)
Adipogénesis/efectos de los fármacos , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Glucósidos/farmacología , Extractos Vegetales/farmacología , Tallos de la Planta/química , Salix/química , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/fisiología , Animales , Proteínas Potenciadoras de Unión a CCAAT/genética , Evaluación Preclínica de Medicamentos , Expresión Génica/efectos de los fármacos , Glucósidos/aislamiento & purificación , Concentración 50 Inhibidora , Metanol/química , Ratones , Obesidad/tratamiento farmacológico , Extractos Vegetales/aislamiento & purificación , Extracción en Fase Sólida , Solventes/química , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética
7.
Food Chem Toxicol ; 58: 355-61, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23688860

RESUMEN

The neuroprotective potential of flavonoids within the brain comprises anti-apoptosis of neuronal cells, anti-neuroinflammation and enhancement of cognitive function. We reported that Rhus vernciflua inhibits glutamate-induced neurotoxicity in primary cultured rat cortical cells. Here we narrowed it down to get neuroprotective fractions from the plant yielding flavonoid-rich ethyl acetate fraction (PREF). Among its active flavonoids, fisetin exhibited not only inhibitory effect against lipopolysaccharide (LPS)-induced neuroinflammation by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also memory enhancing effects via reactivation of cAMP responsive element binding protein (CREB)-brain derived neurotrophic factor (BDNF) pathway in memory-impaired mice by scopolamine. Butein also showed a similar activity to fisetin even though to a lesser extent. The neuroprotection by PREF and selected flavonoids may involve maintenance of antioxidant defense mechanism including glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD). Conclusively, we demonstrate the R. vernciflua bark extract and its active flavonoids with potent neuroprotective and anti-inflammatory effects might be good therapeutic candidates as cognitive-enhancers.


Asunto(s)
Antiinflamatorios/farmacología , Cognición/efectos de los fármacos , Flavonoides/farmacología , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Rhus/química , Animales , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión , Masculino , Ratones , Ratones Endogámicos ICR , Proteínas del Tejido Nervioso/metabolismo , Estrés Oxidativo/efectos de los fármacos , Corteza de la Planta/química , Escopolamina/farmacología
8.
Phytomedicine ; 19(14): 1315-20, 2012 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-23079232

RESUMEN

Diarylheptanoids have been the center of the intensive research efforts for Alzheimer's disease and other neurodegenerative diseases. The present study aimed to determine the effect of the standardized extract of B. platyphylla bark and its major diarylheptanoids in scopolamine-induced amnesic mice through cyclic AMP response element-binding protein (CREB) activation. Oral administration of the standardized extract of B. platyphylla bark (100mg/kg body weight), aceroside VIII (1mg/kg body weight) and platyphylloside (1 or 2mg/kg body weight) significantly ameliorated scopolamine-induced amnesia in passive avoidance test. CREB phosphorylation and brain-derived neurotrophic factor (BDNF) expression in the cortex and hippocampus of the scopolamine-treated mice were markedly increased by the treatment of the standardized extract of B. platyphylla bark and platyphylloside. The standardized extract of B. platyphylla bark and its major diarylheptanoids also significantly protected HT22 cells against neurotoxicity induced by glutamate insult. The standardized extract of B. platyphylla bark and platyphylloside may ameliorate memory deficits by activating the CREB-BDNF pathway and prevent a neurodegeneration by inhibiting neuronal cell death.


Asunto(s)
Amnesia/prevención & control , Betula/química , Cognición/efectos de los fármacos , Diarilheptanoides/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Administración Oral , Amnesia/inducido químicamente , Amnesia/metabolismo , Animales , Reacción de Prevención/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Muerte Celular/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Diarilheptanoides/farmacología , Ácido Glutámico , Masculino , Ratones , Ratones Endogámicos ICR , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/prevención & control , Fármacos Neuroprotectores/farmacología , Corteza de la Planta , Extractos Vegetales/farmacología , Estándares de Referencia , Escopolamina , Transducción de Señal
9.
Phytother Res ; 26(7): 974-80, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22144089

RESUMEN

Regardless of the etiology, cellular death of the liver parenchymal hepatocyte seems to be a primary event of hepatic fibrogenesis, which ultimately results in hepatic stellate cell (HSC) activation and the synthesis of extracellular matrix proteins. Recently it has been demonstrated that hepatic fibrosis can be a reversible process when the stimulus is properly eliminated. Apoptotic removal of active HSC is considered an essential part of the resolution. By employing the HSC cell line, HSC-T6, it was found that the methanol extract of Dendrobium nobile stem significantly inhibited the proliferation of HSC-T6 cells. Three phenanthrenes, denbinobin, fimbriol B and 2,3,5-trihydroxy-4,9-dimethoxyphenanthrene isolated from D. nobile were proven to inhibit HSC proliferation. Growth arrest of HSCs by these compounds was accompanied by cellular loss via autophagy-linked apoptosis. The maximal dose of these compounds, however, had little effect on primary cultured hepatocytes in rats. Collagen deposition in HSC-T6 cells was attenuated by these phenanthrenes. Collectively, the above results demonstrated that denbinobin, fimbriol B and 2,3,5-trihydroxy-4,9-dimethoxyphenanthrene exhibited antifibrotic activities possibly by the induction of selective cell death in HSCs but not in hepatocytes, implying that these compounds may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis.


Asunto(s)
Antraquinonas/farmacología , Apoptosis/efectos de los fármacos , Dendrobium/química , Células Estrelladas Hepáticas/efectos de los fármacos , Fenantrenos/farmacología , Animales , Autofagia/efectos de los fármacos , Línea Celular , Supervivencia Celular , Colágeno/metabolismo , Hepatocitos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Extractos Vegetales/farmacología , Ratas , Factor de Necrosis Tumoral alfa/metabolismo
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