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Inhibitory Activities of Ononin on Particulate Matter-induced Oxidative Stress

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Abstract

Exposure to high levels of atmospheric particulate matter (PM) with an aerodynamic diameter of less than 2.5 µm (PM2.5) is associated with increased risk of respiratory injury, hospitalization, and respiratory death. The mechanism underlying the correlation between PM2.5 exposure and adverse health effects has not been fully elucidated, but oxidative stress due to PM2.5 appears to be an important molecular mechanism in PM2.5-mediated toxicity. The aim of this study was to determine the effects of ononin, a major isoflavone, on PM2.5-induced oxidative stress, and the mechanisms underlying these effects. Human pulmonary artery endothelial cells (HPAECs) were treated with PM2.5 and then ononin. Exposure to PM2.5 decreased cell viability in HPAECs in a time- and dose-dependent manner, possibly due to increased release of extracellular lactate dehydrogenase and generation of intracellular reactive oxygen species. PM2.5-induced oxidative damage was observed to occur via alterations to superoxide dismutase and catalase activities. Serum- and glucocorticoid-inducible kinase 1 (SGK1), a crucial cell survival factor, was downregulated by PM2.5. However, ononin treatment increased cell viability, decreased oxidative stress, and recovered the expression of SGK1 cell survival genes. Additionally, ononin increased the phosphorylation of mammalian target of rapamycin (mTOR) and dramatically suppressed the PM2.5-induced expression of toll-like receptor 4, MyD88, and the autophagy-related proteins LC3 II and Beclin 1. These findings indicate that ononin exhibits pulmonary protective effects against PM2.5-induced lung injury via inhibition of oxidative stress and mTOR-dependent autophagy pathways and is thus a potential therapeutic agent for PM2.5-induced lung injury.

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Acknowldgments

This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C0001) and by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2020R1A2C1004131).

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  1. College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu, 41566, Korea

    Wonhwa Lee, Samyeol Choo, Hyunchae Sim & Jong-Sup Bae

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  1. Wonhwa Lee
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Correspondence to Jong-Sup Bae.

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Lee, W., Choo, S., Sim, H. et al. Inhibitory Activities of Ononin on Particulate Matter-induced Oxidative Stress. Biotechnol Bioproc E 26, 208–215 (2021). https://doi.org/10.1007/s12257-020-0294-0

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