β-Asarone Alleviates High-Glucose-Induced Oxidative Damage via Inhibition of ROS Generation and Inactivation of the NF-κB/NLRP3 Inflammasome Pathway in Human Retinal Pigment Epithelial Cells

• Published in: Antioxidants 2023-07, Vol.12 (7), p.1410
• Main Authors: Park, Cheol, Cha, Hee-Jae, Hwangbo, Hyun, Bang, EunJin, Hong, Su Hyun, Song, Kyoung Seob, Noh, Jeong Sook, Kim, Do-Hyung, Kim, Gi-Young, Choi, Yung Hyun
• Format: Article
• Language: English
• Subjects: Apoptosis; Asarones; Caspase; Cell culture; Cytotoxicity; Dextrose; Diabetes; Diabetes mellitus; DNA damage; Flow cytometry; Glucose; Glutathione; high glucose; Hyperglycemia; Inflammasomes; Inflammation; Interleukin 18; L-Lactate dehydrogenase; Manganese; Microscopy; Morphology; NF-κB; NF-κB protein; NLRP3 inflammasome; Oxidative stress; Pathogenesis; Proteins; Pyrin protein; Reactive oxygen species; Reagents; Retina; Retinal pigment epithelium; Retinopathy; Risk factors; ROS; Scientific equipment and supplies industry; Signal transduction; Superoxide; Thioredoxin; β-asarone
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox12071410

Diabetic retinopathy (DR) is the leading cause of vision loss and a major complication of diabetes. Hyperglycemia-induced accumulation of reactive oxygen species (ROS) is an important risk factor for DR. β-asarone, a major component of volatile oil extracted from Rhizoma, exerts antioxidant effects; however, its efficacy in DR remains unknown. In this study, we investigated whether β-asarone inhibits high-glucose (HG)-induced oxidative damage in human retinal pigment epithelial (RPE) ARPE-19 cells. We found that β-asarone significantly alleviated cytotoxicity, apoptosis, and DNA damage in HG-treated ARPE-19 cells via scavenging of ROS generation. β-Asarone also significantly attenuated the excessive accumulation of lactate dehydrogenase and mitochondrial ROS by increasing the manganese superoxide dismutase and glutathione activities. HG conditions markedly increased the release of interleukin (IL)-1β and IL-18 and upregulated their protein expression and activation of the nuclear factor-kappa B (NF-κB) signaling pathway, whereas β-asarone reversed these effects. Moreover, expression levels of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome multiprotein complex molecules, including thioredoxin-interacting protein, NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, and cysteinyl aspartate-specific proteinase-1, were increased in ARPE-19 cells under HG conditions. However, their expression levels remained similar to those in the control group in the presence of β-asarone. Therefore, β-asarone protects RPE cells from HG-induced injury by blocking ROS generation and NF-κB/NLRP3 inflammasome activation, indicating its potential as a therapeutic agent for DR treatment.