RESUMEN
Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes. This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice. AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes. Protein levels of O-linked ß-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting. Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis. Interaction between ChREBP and OGT was assessed using coimmunoprecipitation analysis. AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas. AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas. Coimmunoprecipitation analysis indicated that AES extract reduced interaction between ChREBP and OGT and attenuated ganglion cell death in diabetic retinas. Moreover, the ChREBP that colocalized with OGT or the TUNEL signal was significantly decreased in diabetic mice treated with AES extract. These findings show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related retinal injury in diabetic retinopathy.
Asunto(s)
Aralia/química , Retinopatía Diabética/tratamiento farmacológico , N-Acetilglucosaminiltransferasas/metabolismo , Extractos Vegetales/administración & dosificación , Retina/enzimología , Animales , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Muerte Celular/efectos de los fármacos , Retinopatía Diabética/genética , Retinopatía Diabética/metabolismo , Glucosa/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , N-Acetilglucosaminiltransferasas/genética , Retina/citología , Retina/efectos de los fármacos , Retina/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Tiorredoxinas/genética , Tiorredoxinas/metabolismoRESUMEN
BACKGROUND: To measure ascorbic acid concentration in aqueous humor of patients with cataract after oral or intravenous vitamin C supplementation. METHODS: Forty-two eyes of 42 patients with senile cataract who underwent uncomplicated cataract surgery were enrolled. Patients (n = 14 each) were administered oral vitamin C (2 g), intravenous vitamin C (20 g) or no treatment (control group) on the day before surgery. Samples of aqueous humor (0.1 cm3) were obtained by anterior chamber aspiration at the beginning of surgery and stored at -80 °C. Ascorbic acid concentration in aqueous humor was measured by high-pressure liquid chromatography. RESULTS: The mean age at surgery was 62.5 years, with no difference among the three groups. The mean ± standard deviation concentrations of ascorbic acid in aqueous humor in the control and oral and intravenous vitamin C groups were 1347 ± 331 µmol/L, 1859 ± 408 µmol/L and 2387 ± 445 µmol/L, respectively. Ascorbic acid concentration was significantly lower in the control than in the oral (P < 0.01) and intravenous (P < 0.001) vitamin C groups and was significantly higher in the intravenous than in the oral vitamin C group (P < 0.05). CONCLUSIONS: Ascorbic acid concentration in aqueous humor is increased by systemic vitamin C supplementation, with intravenous administration being more effective than oral administration.
Asunto(s)
Humor Acuoso/química , Ácido Ascórbico/farmacocinética , Catarata/dietoterapia , Administración Oral , Antioxidantes/administración & dosificación , Antioxidantes/farmacocinética , Ácido Ascórbico/administración & dosificación , Biomarcadores/metabolismo , Catarata/metabolismo , Extracción de Catarata , Cromatografía Líquida de Alta Presión , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios ProspectivosRESUMEN
BACKGROUND/AIMS: The present study addresses the role of tonicity response element binding protein (TonEBP) in retinal ganglion cell (RGC) death in diabetic retinopathy and the impact of Aralia elata extract on the TonEBP/RGC interaction. METHODS: Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). Control mice received phosphate-buffered saline. After five injections of STZ or saline buffer, A. elata extract was administered by daily oral tube feeding for 7 weeks. All mice were killed at 2 months after the last injection of STZ or saline and the extent of cell death together with the protein expression levels of TonEBP, aldose reductase (AR) and nuclear factor-kappa B (NF-κB) were examined. RESULTS: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive signals were colocalized with TonEBP-immunoreactive RGCs. The apoptotic cell death of RGCs and the expression levels of TonEBP, AR and NF-κB were significantly increased in the retinas of diabetic mice compared with controls at 2 months after the induction of diabetes. However, these changes were effectively blocked by the administration of A. elata extract. CONCLUSIONS: These results indicate that A. elata prevents diabetes-induced RGC apoptosis and downregulates TonEBP expression. Therefore, A. elata extract may have therapeutic potential to prevent diabetes-induced retinal neurodegeneration in diabetic retinopathy.
Asunto(s)
Aralia , Diabetes Mellitus Experimental/complicaciones , Retinopatía Diabética/metabolismo , Factores de Transcripción NFATC/metabolismo , Extractos Vegetales/farmacología , Células Ganglionares de la Retina/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Retinopatía Diabética/tratamiento farmacológico , Regulación hacia Abajo , Ratones , Ratones Endogámicos C57BL , Retina/efectos de los fármacos , Retina/metabolismo , Células Ganglionares de la Retina/metabolismoRESUMEN
The objective of this study was to determine the effect of vitamin C supplementation on reducing the size of corneal opacity resulting from infectious keratitis.The study included 82 patients (82 affected eyes), admitted for infectious keratitis from January 2009 to August 2013, who were followed for more than 3 months. Patients were divided into control, oral vitamin C (3 g/d), and intravenous vitamin C (20 g/d) groups during hospitalization. Corneal opacity sizes were measured using anterior segment photographs and Image J program (version 1.27; National Institutes of Health, Jinju, South Korea) at admission, discharge, and final follow-up. The corneal opacity size used for analysis was the measured opacity size divided by the size of the whole cornea.The corneal opacity size decreased by 0.03 ± 0.10 in the oral vitamin C group, 0.07 ± 0.22 in the intravenous vitamin C group, and 0.02 ± 0.15 in the control group. Intravenous vitamin C reduced the corneal opacity size more than oral vitamin C (P = 0.043). Intravenous vitamin C produced greater reduction in corneal opacity size in younger patients (P = 0.015) and those with a hypopyon (P = 0.036).Systemic vitamin C supplementation reduced the size of corneal opacity resulting from infectious keratitis. Intravenous vitamin C was more beneficial than oral supplementation, especially in younger patients and those with hypopyon.