Activation of Heme Oxygenase-1 is Involved in the Preventive Effect of Honokiol against Oxidative Damage in Human Retinal Pigment Epithelial Cells

• Published in: Biotechnology and bioprocess engineering Vol. 27; no. 6; pp. 975 - 986
• Main Authors: Hong, Su Hyun, Park, Cheol, Hwangbo, Hyun, Bang, EunJin, Kim, Sung Ok, Shim, Jung-Hyun, Park, Shin-Hyung, Lee, Hyesook, Leem, Sun-Hee, Kim, Gi-Young, Choi, Yung Hyun
• Format: Journal Article
• Language: English
• Published: Seoul The Korean Society for Biotechnology and Bioengineering 01.12.2022; Springer Nature B.V
• Subjects: antioxidant activity; Antioxidants; Apoptosis; Bcl-2 protein; Bioactive compounds; Biocompatibility; Biotechnology; Cell cycle; cell cycle checkpoints; Cell viability; Chemistry; Chemistry and Materials Science; Chronic illnesses; Cytochrome c; Cytochromes; Cytoplasm; Cytotoxicity; Damage; DNA damage; Epithelium; Heme; heme oxygenase (biliverdin-producing); Heme oxygenase (decyclizing); honokiol; humans; Hydrogen peroxide; Industrial and Production Engineering; Magnolia; Membrane potential; Mitochondria; mitochondrial membrane; Myoblasts; Oxidative stress; Oxygenase; Phosphorylation; Protoporphyrin; Reactive oxygen species; Research Paper; Retina; Retinal pigment epithelium; Toxicity; zinc; retinal pigment epithelial cells; honokiol; reactive oxygen species; Nrf2/HO-1
• ISSN: 1226-8372; 1976-3816
• DOI: 10.1007/s12257-022-0174-x

Previous studies have shown that honokiol, a bioactive compound originated from the Magnolia , has beneficial effects on various chronic diseases. Although our previous study has demonstrated that honokiol effectively protects C2C12 myoblasts against hydrogen peroxide (H 2 O 2 )-induced oxidative stress and cytotoxicity, the antioxidant mechanism in human retinal pigment epithelial (RPE) cells has not been reported yet. Therefore, this study investigates whether honokiol attenuate cytotoxicity of H 2 O 2 to human RPE ARPE-19 cells. Our results showed that H 2 O 2 -induced loss of cell viability and increase of reactive oxygen species production in ARPE-19 cells were significantly alleviated by honokiol, which was associated with increased phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulation of heme oxygenase-1 (HO-1). In addition, honokiol markedly attenuated DNA damage and G2/M phase cell cycle arrest and improved apoptosis in H 2 O 2 -treated ARPE-19 cells. Furthermore, mitochondrial dysfunction by H 2 O 2 was reversed by honokiol through preservation of mitochondrial membrane potential, decrease of Bax/Bcl-2 expression ratio, and inhibition of cytochrome c release into the cytoplasm. However, zinc protoporphyrin, an inhibitor of HO-1, significantly abrogated these preventive effects, suggesting a critical role of Nrf2/HO-1 in the antioxidant activity of honokiol. Taken together, these results demonstrate that activation of Nrf2/HO-1 antioxidant signaling by honokiol could rescue ARPE-19 cells from oxidative damage.