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

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Abstract

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 (H2O2)-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 H2O2 to human RPE ARPE-19 cells. Our results showed that H2O2-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 H2O2-treated ARPE-19 cells. Furthermore, mitochondrial dysfunction by H2O2 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.

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Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) Grant funded by the Korea government (NRF-2020R1A2C1099910 and NRF-2021R1A2C200954911).

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Author notes

  1. Su Hyun Hong and Cheol Park contributed equally to this work.

Authors and Affiliations

  1. Anti-Aging Research Center, Dong-eui University, Busan, 47340, Korea

    Su Hyun Hong, Hyun Hwangbo, EunJin Bang & Yung Hyun Choi

  2. Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, 47227, Korea

    Su Hyun Hong, Hyun Hwangbo, EunJin Bang & Yung Hyun Choi

  3. Division of Basic Sciences, College of Liberal Studies, Dong-eui University, Busan, 47340, Korea

    Cheol Park

  4. Department of Food Science and Biotechnology, College of Engineering, Kyungsung University, Busan, 48434, Korea

    Sung Ok Kim

  5. Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan, 58554, Korea

    Jung-Hyun Shim

  6. Department of Pathology, Dong-eui University College of Korean Medicine, Busan, 47227, Korea

    Shin-Hyung Park

  7. Department of Convergence Medicine, Pusan National University School of Medicine, Yangsan, 50612, Korea

    Hyesook Lee

  8. Department of Biological Science, Dong-A University, Busan, 49315, Korea

    Sun-Hee Leem

  9. Department of Health Sciences, The Graduated of Dong-A University, Busan, 49315, Korea

    Sun-Hee Leem

  10. Department of Marine Life Science, Jeju National University, Jeju, 63243, Korea

    Gi-Young Kim

  11. Core-Facility Center for Tissue Regeneration, Dong-eui University, Busan, 47340, Korea

    Yung Hyun Choi

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  1. Su Hyun Hong
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Hong, S.H., Park, C., Hwangbo, H. et al. Activation of Heme Oxygenase-1 is Involved in the Preventive Effect of Honokiol against Oxidative Damage in Human Retinal Pigment Epithelial Cells. Biotechnol Bioproc E 27, 975–986 (2022). https://doi.org/10.1007/s12257-022-0174-x

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