Hawthorn polyphenols reduce high glucose‐induced inflammation and apoptosis in ARPE‐19 cells by regulating miR‐34a/SIRT1 to reduce acetylation

Abstract

Diabetic retinopathy is a major complication in patients with diabetes. Herein, we investigate how hawthorn polyphenol extract (HPE) affects high glucose-induced oxidation, inflammation, and apoptosis in ARPE-19 cells. HPLC-MS/MS was used to determine HPE content and composition. Reactive oxygen species (ROS) production was assessed using fluorescence microscopy, while glucose-induced gene and protein expressions were analyzed using real-time PCR and western blotting in cells transfected with miR-34a mimics. We found that treating cells with 10 μg/ml of HPE, 30 μM procyanidin B2, chlorogenic acid, epicatechin, or resveratrol (positive control) significantly reduced ROS production and decreased apoptosis and inflammationrelated factors (p < .01). Moreover, the expression level of SIRT1 was increased, while that of acetylated NF-κB p65 and p53 proteins was decreased. These data suggest that HPE can inhibit oxidative damage, inflammation, and apoptosis through the AMPK/SIRT1/NF-κB pathway, and decrease miR-34a/SIRT1/p53 pathway activation in ARPE-19 cells, thereby demonstrating a potential use as a food additive to mitigate hyperglycemia-induced retinal damage. Practical applications Hawthorn polyphenol extract (HPE) significantly reduced ROS levels, apoptosis, and the expression of inflammation-related factors in ARPE-19 cells. HPE also inhibited the AMPK/SIRT1/NF-κB and miR-34a/SIRT1/p53 pathways, which are involved in hyperglycemia-induced inflammation and apoptosis of ARPE-19 cells by regulating acetylation. Thus, HPE, as a potential food additive, may mitigate hyperglycemiainduced retinal damage.

Hawthorn fruit extract protect against MC‐LR‐induced hepatotoxicity by attenuating oxidative stress and apoptosis

“…This study showed that MC‐LR induced mitochondrial destruction and Cyt C release, which could be significantly alleviated by HFE. It has been reported that Hawthorn polyphenols can inhibit hyperglycemia‐induced inflammation and ARPE‐19 cells apoptosis mainly through activation of AMPK/SIRT1/p53 pathways 51 . Polyphenols in hawthorn extract could also inhibit apoptosis by down‐regulating the expression of pro‐apoptotic protein Bax, up‐regulating the expression of anti‐apoptotic protein Bcl‐2, and inhibiting the activation of Caspase‐3/9 52 .…”

Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

“…413 Hawthorn polyphenol extract (HPE) also activates SIRT1 and ameliorates hyperglycaemia-induced retinal damage by suppressing inflammation and apoptosis in ARPE-19 cells via AMPK-SIRT1-NF-κB pathway activation and miR-34a-SIRT1-p53 pathway suppression. 414 Of note, in 2007 Milne et al 415 identified small molecule activators of SIRT1, including SRT1720, which improve insulin sensitivity and decrease plasma glucose, providing a potential treatment for T2D. These small molecule activators of SIRT1 are not structurally similar to resveratrol and are 1,000-fold more potent.…”

The role of protein acetylation in carcinogenesis and targeted drug discovery

“…Plant-derived inhibitors also showed good activity in inhibiting tumors. For example, hawthorn polyphenol extract (HPE) can significantly reduce ROS levels, apoptosis and inflammation-related factor expression in cells, and also inhibit AMPK/SIRT1/NF-κB and miR-34a/SIRT1/p53 pathways by regulating acetylation ( 275 ). Pathway is involved in hyperglycemia-induced inflammation and apoptosis of human retinal epithelial cells ( 275 ).…”

“…For example, hawthorn polyphenol extract (HPE) can significantly reduce ROS levels, apoptosis and inflammation-related factor expression in cells, and also inhibit AMPK/SIRT1/NF-κB and miR-34a/SIRT1/p53 pathways by regulating acetylation ( 275 ). Pathway is involved in hyperglycemia-induced inflammation and apoptosis of human retinal epithelial cells ( 275 ). These inhibitors can significantly inhibit tumor proliferation, migration and invasion, and can induce apoptosis and induce autophagy ( 59 ).…”