Curcumin inhibits high glucose‑induced inflammatory injury in human retinal pigment epithelial cells through the ROS‑PI3K/AKT/mTOR signaling pathway

Abstract

Diabetic retinopathy (DR) is a retinal disease caused by metabolic disorders of glucose tolerance that can lead to irreversible blindness if not adequately treated. Retinal pigment epithelial cell (RPEC) dysfunction contributes to the pathogenesis of DR. In the present study the anti-inflammatory effect of curcumin (CUR) was investigated in RPECs damaged by high glucose levels. RPEC treated with 30 mmol/l glucose was regarded as high glucose group, and cells treated with 24.4 mmol/l mannitol was set as equivalent osmolarity group. Cell Counting Kit-8 assay was used to measure RPEC viability, the expression of phosphorylated (p)-AKT and p-mammalian target of rapamycin (mTOR) were assessed by western blot, and secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in the culture medium was measured by ELISA. Intracellular reactive oxygen species (ROS) levels were measured by laser scanning confocal microscope. The present data indicated that, compared with mannitol treatment, high glucose treatment reduced RPEC viability, increased TNF-α, IL-6 and IL-1β secretion, increased ROS formation and promoted phosphorylation of AKT and mTOR. The antioxidant N-acetylcysteine, the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002 and the mTOR inhibitor rapamycin ameliorated the effects of high glucose. In addition, pretreatment with 10 µmol/l CUR reduced secretion levels of TNF-α, IL-6 and IL-1β, ROS formation and phosphorylation of AKT and mTOR. In conclusion, CUR inhibited high glucose-induced inflammatory injury in RPECs by interfering with the ROS/PI3K/AKT/mTOR signaling pathway. The present study may reveal the molecular mechanism of CUR inhibition effects to high glucose-induced inflammatory injury in RPEC.

Exploring the Mechanism of Action Compound‐Xueshuantong Capsule in Diabetic Retinopathy Treatment Based on Network Pharmacology

“…At the same time, research from Zhou et al showed that IL-6 and other inflammatory cytokines increased in the vitreous of patients with PDR, which suggested that inflammatory cytokines were closely related to the occurrence and development of PDR [ 26 ]. Research from Ran et al showed that the secretion of inflammatory factors such as IL-6 in retinal pigment epithelial cells treated with high glucose increased [ 27 ].…”

Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies

“…Curcumin is another natural compound, which is a therapeutic candidate for a variety of retinal diseases due to its antioxidant properties [ 253 ]. Ran et al reported that curcumin reduced ROS injury in human RPE cells through the ROS/PI3K/AKT/mTOR signaling pathway [ 254 ]. Cai et al reported that by inhibiting p38 MAPK and NF-κB activation, curcumolide, a unique sesquiterpenoid from curcuma, alleviated retinal vascular permeability and the levels of ROS and TNF-α [ 255 ].…”

Network Pharmacology-based Approach to Comparatively Predict the Active Ingredients and Molecular Targets of Compound Xueshuantong Capsule and Hexuemingmu Tablet in the Treatment of Proliferative Diabetic Retinopathy

“…The PI3K-Akt signaling pathway is one of the most frequently studied pathways in DR [33][34][35]. The proliferation, migration and invasion of retinal vascular endothelial cells, retinal pericytes, retinal pigment epithelial cells and microglial cells can be regulated through this pathway [36][37][38][39]. A series of pathophysiological processes, including oxidative stress regulation, in ammatory response regulation, angiogenesis and neuroprotective regulation, are also involved.…”