Dihydromyricetin Alleviates High Glucose-Induced Oxidative Stress and Apoptosis in Human Retinal Pigment Epithelial Cells by Downregulating miR-34a Expression

Abstract

Background Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus, which leads to neuronal and vascular dysfunction in the retina with a final outcome of complete loss of vision. The aim of the present study was to investigate the effects of dihydromyricetin (DHM), a natural flavanol compound, on diabetic retinopathy (DR) and identify its potential mechanisms. Methods Retinal pigment epithelial cell line (ARPE-19) treated with high glucose (HG) was used to simulate the DR model in vitro. After treatment with different concentrations of DHM, the cell viability, production of reactive oxygen species (ROS) and the levels of oxidative stress-related markers in the in vitro model were detected using corresponding kits. Cell apoptosis was determined using terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining, and the expression of apoptotic proteins was examined using Western blot analysis. Subsequently, microRNA (miR)-34a expression was measured by reverse transcription-quantitative PCR (RT-qPCR). The levels of oxidative stress and apoptosis were evaluated after miR-34a overexpression. Results Results indicated that DHM dose-dependently elevated the decreased cell viability induced by HG. Moreover, the content of ROS was significantly reduced in HG-stimulated ARPE-19 cells, accompanied by enhanced activities of superoxide dismutase (SOD) and catalase (CAT) antioxidases, as well as concentration of glutathione (GSH). Furthermore, remarkably decreased apoptosis of ARPE-19 cells induced by HG was observed following DHM intervention. Importantly, HG stimulation notably upregulated miR-34a expression, which was reversed by DHM treatment. Importantly, the inhibitory effects of DHM on HG-induced oxidative stress and apoptosis of ARPE-19 cells were restored following miR-34a overexpression. Conclusion Taken together, this work demonstrated that DHM exerts protective effects on HG-induced oxidative stress and apoptotic damage in ARPE-19 cells via inhibition of miR-34a expression, providing a promising therapeutic agent for the treatment of DR.

Platycodin D inhibits diabetic retinopathy via suppressing TLR4/MyD88/NF‐κB signaling pathway and activating Nrf2/HO‐1 signaling pathway

“…There is growing evidence pointing to the RPE essential propriety and its impairment in DR (Ponnalagu et al., 2017). HG results in oxidative stress and inflammation, as well as induces apoptosis in ARPE‐19 cells (Li & Xiao, 2021; Shi et al., 2020; Zhang et al., 2022). Similar findings were observed in our study as well, where both ROS, TNF‐α, IL‐1β, and IL‐6 levels and cell apoptosis increased in HG treatment group.…”

Oxidative Stress and Its Regulation in Diabetic Retinopathy

“…MicroRNA regulate the expression of many gene transcripts in the context of diabetic retinopathy, and the connection between miRNA and oxidative stress in diabetic retinopathy is well established [ 165 ]. New research has implicated miRNA regulation in the mechanism of antioxidant activity of plant extracts [ 166 , 167 ], and flavonol compounds [ 168 ] in the ARPE-19 cell line. An investigation of the antioxidant activity of 25-hydroxyvitamin D3 (vitamin D) in human retinal endothelial cells revealed a reduction in miR-93 transcript with high glucose and vitamin D treatment, compared to high glucose alone, as well as reduced ROS production, malondialdehyde (MDA) content, and an increased level of reduced glutathione (GSH) [ 169 ].…”

Alleviate oxidative stress in diabetic retinopathy: antioxidant therapeutic strategies

“…Dihydromyricetin (DMY), a flavonoid found in Ampelopsis grossedentata, has antioxidant, anti-angiogenic, and anti-inflammatory properties that suggest it may be beneficial for inhibiting the progression of diabetes and treating related complications [ 67 ]. A previous study has shown that DHM protects against HG-induced oxidative stress and apoptotic damage in RPE cell line cells via inhibiting miR-34a expression [ 68 ]. Our laboratory has reported for the first-ever the construction of ultra-small Fe-DMY nanoparticles (Fe-DMY NCPs), which are composed of DMY combined with low-toxicity iron ions.…”