Lycium barbarum увеличивает калорийность расходы и уменьшает окружность талии у здоровых полных мужчин и женщин: пилотное исследование

Abstract

Diabetic retinopathy is a preventable microvascular diabetic complication and a leading cause of vision loss. Retinal pigment epithelial cell apoptosis is an early event in diabetic retinopathy. Taurine is reportedly beneficial for diabetic retinopathy and is abundant in the fruit of Lycium barbarum (LB). We have investigated the effect of pure taurine and an extract of LB rich in taurine on a model of diabetic retinopathy, the retinal ARPE-19 cell line exposed to high glucose. We demonstrate for the first time that LB extract and the active ligand, taurine, dose dependently enhance cell viability following high glucose treatment in the ARPE-19 retinal epithelial cell line. This cytoprotective effect was associated with the attenuation of high glucose-induced apoptosis, which was shown by characteristic morphological staining and the dose-dependent decrease in the number of apoptotic cells, determined by flow cytometry. Moreover, we have shown that LB extract and taurine dose dependently downregulate caspase-3 protein expression and the enzymatic activity of caspase-3. We conclude that taurine, a major component of LB, and the LB extract, have a cytoprotective effect against glucose exposure in a human retinal epithelial cell line and may provide useful approaches to delaying diabetic retinopathy progression.

1. 
   Introduction
   

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and remains a major cause of preventable blindness worldwide [1]. Diabetes damages all the major cells of the retina and pigment epithelial cells [2]. This results in increased blood flow and capillary diameter, proliferation of the extracellular matrix and thickening of basal membranes, altered cell turnover (apoptosis, proliferation), and breakdown of the blood retinal barrier [3].

Apoptosis or programmed cell death can be triggered by various signals and is characterized by well-defined morphologic changes, including chromatin condensation and fragmentation, and formation of apoptotic bodies [4]. Retinal microvascular cells are lost selectively via apoptosis before other histopathology is detectable in diabetes [5]. Moreover, recent findings have suggested that apoptotic episodes in retinal cells during the initial stage of diabetes play an integral role in the early stage of vision loss [6]. Therefore, apoptosis is important in the progression and pathogenesis of DR [7].

Retinal pigment epithelial (RPE) cells form a monolayer between the neuroretina and the choriocapillaris, which are the essential components of the outer blood retinal barrier (BRB) that maintains physiological and structural balance within the retina [8]. RPE cells are particularly susceptible to oxidative stress because of high oxygen consumption by photoreceptors [9]. Moreover, recent studies have shown that RPE cells undergo oxidative stress and UV-light induced apoptosis [10, 11]. Although several studies have shown that RPE degenerates in the early stage of diabetes [12, 13], the mechanisms of high-glucose-induced apoptosis in RPE cell models of DR are not fully understood.

High glucose causes activation of several proteins involved in apoptotic cell death, including members of the caspase family [14]. It is well known that caspases are involved in the initiation and execution of apoptosis [15]. Moreover, the widely studied caspase-3 plays an important role in diabetes [16].

Recent studies have suggested that ligand-activated PPAR-γ controls apoptosis, contributing to tissue protection [17]. Indeed, it has been shown that the PPAR-γ agonist rosiglitazone protects against oxidative stress-induced apoptosis through upregulation of antiapoptotic Bcl-2 family proteins [18]. Troglitazone showed a cytoprotective activity from oxidative stress-induced apoptosis in ARPE-19 cells [19]. Moreover, the study has shown that a natural ligand, 15-deoxy-delta-12,14-prostaglandin J₂ (15d-PGJ₂), helps RPE cells to maintain mitochondrial integrity by prevention of cytochrome c (cyt c) release from mitochondria and subsequent activation of the apoptosis pathway [20].

Fruits from Lycium barbarum L. (LB) in the family Solanaceae are a well-known traditional Chinese medicine which has glucose-lowering activity and antiapoptotic activity [21]. There is a growing body of evidence indicating that LB intake increases the fasting plasma zeaxanthin levels, beneficial for maintaining macular pigment density in age-related macular degeneration [22]. Moreover, polysaccharides of LB (LBP) increase antiapoptotic protein Bcl-2 levels in lens epithelial cells [23]. LB contains 18 types of amino acids, including taurine, a nonessential free amino acid, which is one of the chemical components most abundant in LB [24, 25]. Taurine has been recommended as a complementary therapeutic agent for the prevention of diabetic complications in type II diabetes [26]. Moreover, it has been shown that taurine inhibits the activation of caspase-3 in ischemic cardiomyocytes [27]. Taurine has also been found to prevent high-glucose-mediated endothelial cell apoptosis through its antioxidant property [28]. Recently, we have shown that LB extract and pure taurine, a major component in the LB extract, activated PPAR-γ by luciferase reporter gene analysis and by mRNA and western blotting measurement in human retinal pigment epithelial cells. At the same time, both LB extract and pure taurine inhibited a variety of PPAR-γ-dependent downstream effectors in the retinal cells [29]. However, the pathways of the beneficial effect of LB and its taurine active component on DR by modulation of high-glucose-induced apoptosis through the PPAR-γ-mediated caspase-3 pathway have not been investigated. Therefore, the aim of this study is to investigate the cytoprotective effect of pure taurine and an extract of LB rich in taurine against glucose exposure in a human retinal epithelial cell line as a model of DR.