Polyphenol-enriched cocoa protects the diabetic retina from glial reaction through the sirtuin pathway

Author(s)

Duarte, Diego A. ^[1] ; Rosales, Mariana Ap. B. ^[1] ; Papadimitriou, Alexandros ^[1] ; Silva, Kamila C. ^[1] ; Amancio, Vitor Hugo O. ^[1] ; Mendonca, Jacqueline N. ^[2] ; Lopes, Norberto P. ^[2] ; Lopes de Faria, Jose B. ^[1] ; Lopes de Faria, Jacqueline M. ^[1]

Affiliation

^[1] Univ Estadual Campinas, Fac Med Sci, Renal Pathophysiol Lab, BR-13083970 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, Nucleo Pesquisa Prod Nat & Sintet, BR-14049 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF NUTRITIONAL BIOCHEMISTRY; v. 26, n. 1, p. 64-74, JAN 2015.
• Web of Science Citations: 23

Abstract

Cocoa is rich in flavonoids, which are potent antioxidants with established benefits for cardiovascular health but unproven effects on neurodegeneration. Sirtuins (SIRTs), which make up a family of deacetylases, are thought to be sensitive to oxidation. In this study, the possible protective effects of cocoa in the diabetic retina were assessed. Rat Muller cells (rMCs) exposed to normal or high glucose (HG) or H2O2 were submitted to cocoa treatment in the presence or absence of SIRT-1 inhibitor and small interfering RNA The experimental animal study was conducted in streptozotocin-induced diabetic rats randomized to receive low-, intermediate-, or high-polyphenol cocoa treatments via daily gavage for 16 weeks (i.e., 0.12, 2.9 or 22.9 mg/kg/day of polyphenols). The rMCs exposed to HG or H2O2 exhibited increased glial fibrillary acidic protein (GFAP) and acetyl-RelA/p65 and decreased SIRT1 activity/expression. These effects were cancelled out by cocoa, which decreased reactive oxygen species production and PARP-1 activity, augmented the intracellular pool of NAD(+), and improved SIRT1 activity. The rat diabetic retinas displayed the early markers of retinopathy accompanied by markedly impaired electroretinogram. The presence of diabetes activated PARP-1 and lowered NAD(+) levels, resulting in SIRT1 impairment. This augmented acetyl RelA/p65 had the effect of up-regulated GFAP. Oral administration of polyphenol cocoa restored the above alterations in a dose-dependent manner. This study reveals that cocoa enriched with polyphenol improves the retinal SIRT-1 pathway, thereby protecting the retina from diabetic milieu insult. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 09/51812-0 - Development of a platform for the study of in vitro and in vivo metabolism of natural products, a need for pre-clinical testing system
• Grantee: Norberto Peporine Lopes
• Support type: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 08/57560-0 - Effects of green tea (Camellia sinensis), cocoa and nitric oxide donor on diabetic nephropathy and retinopathy: contribution of the reduction of oxidative stress and inflammation and elevation of nitric oxide
• Grantee: Jose Butori Lopes de Faria
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 10/11514-7 - Does green tea (Camellia sinensis, CS) present neuroprotector effect in the pathogenesis of diabetic retinopathy? In vitro studies in primary rat Muller cell culture to investigate the possible molecular mechanisms involved in neuroprotective effects of CS
• Grantee: Jacqueline Mendonça Lopes de Faria
• Support type: Regular Research Grants