EMAIL THIS PAGE TO A FRIEND

The Journal of nutrition

Ocular inflammation and endoplasmic reticulum stress are attenuated by supplementation with grape polyphenols in human retinal pigmented epithelium cells and in C57BL/6 mice.


PMID 24699803

Abstract

Inflammation and endoplasmic reticulum (ER) stress are common denominators for vision-threatening diseases such as diabetic retinopathy and age-related macular degeneration. Based on our previous study, supplementation with muscadine grape polyphenols (MGPs) alleviated systemic insulin resistance and proinflammatory responses. In this study, we hypothesized that MGPs would also be effective in attenuating ocular inflammation and ER stress. We tested this hypothesis using the human retinal pigmented epithelium (ARPE-19) cells and C57BL/6 mice. In ARPE-19 cells, tumor necrosis factor-α-induced proinflammatory gene expression of interleukin (IL)-1β, IL-6, and monocyte chemotactic protein-1 was decreased by 35.0%, 68.8%, and 62.5%, respectively, with MGP pretreatment, which was primarily due to the diminished mitogen-activated protein kinase activation and subsequent reduction of nuclear factor κ-B activation. Consistently, acute ocular inflammation and leukocyte infiltration were almost completely dampened (>95%) by MGP supplementation (100-200 mg/kg body weight) in C57BL/6 mice. Moreover, MGPs reduced inflammation-mediated loss of tight junctions and retinal permeability. To further investigate the protective roles of MGPs against ER stress, ARPE-19 cells were stimulated with thapsigargin. Pretreatment with MGPs significantly decreased the following: 1) ER stress-mediated vascular endothelial growth factor secretion (3.47 ± 0.06 vs. 1.58 ± 0.02 μg/L, P < 0.0001), 2) unfolded protein response, and 3) early apoptotic cell death (64.4 ± 6.85 vs. 33.7 ± 4.32%, P = 0.0003). Collectively, we have demonstrated that MGP is effective in attenuating ocular inflammation and ER stress. Our work also suggests that MGP may provide a novel dietary strategy to prevent vision-threatening retinal diseases.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

E2250
Ellagic acid, ≥95% (HPLC), powder, from tree bark
C14H6O8
14668
Ellagic acid, analytical standard
C14H6O8
RAB0507
Human VEGF ELISA Kit, for serum, plasma, cell culture supernatants and urine
RAB0508
Human VEGF ELISA Kit, for cell and tissue lysates
RAB0328
Human VEGF R2 ELISA Kit, for serum, plasma, cell culture supernatant and urine
RAB0195
Human VEGF R3 ELISA Kit, for serum, plasma, cell culture supernatant, urine
96353
Kaempferol, analytical standard
C15H10O6
00550580
Kaempferol, primary reference standard
C15H10O6
60010
Kaempferol, ≥97.0% (HPLC)
C15H10O6
K0133
Kaempferol, ≥90% (HPLC), powder
C15H10O6
RAB0509
Mouse VEGF ELISA Kit, for serum, plasma, cell culture supernatant
RAB0510
Mouse VEGF ELISA Kit, for cell and tissue lysates
RAB0192
Mouse VEGF R1 ELISA Kit, for serum, plasma and cell culture supernatants
72576
Myricetin, analytical standard
C15H10O8
M6760
Myricetin, ≥96.0%, crystalline
C15H10O8
70050
Myricetin, ≥96.0% (HPLC)
C15H10O8
PHR1488
Quercetin, Pharmaceutical Secondary Standard; Certified Reference Material
C15H10O7 · xH2O
1592409
Quercetin, United States Pharmacopeia (USP) Reference Standard
C15H10O7 · 2H2O
Q4951
Quercetin, ≥95% (HPLC), solid
C15H10O7
RAB0511
Rat VEGF ELISA Kit, for serum, plasma and cell culture supernatant
RAB0512
Rat VEGF ELISA Kit, for cell and tissue lysates
SRP3177
TNF-α human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), cell culture tested
T0157
Tumor Necrosis Factor-α human, TNF-α, recombinant, expressed in yeast, buffered aqueous solution, suitable for cell culture
T6674
Tumor Necrosis Factor-α human, TNF-α, recombinant, expressed in E. coli, powder, suitable for cell culture
H8916
Tumor Necrosis Factor-α human, TNF-α, recombinant, expressed in HEK 293 cells, HumanKine®, suitable for cell culture