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Liquiritin alleviates LPS-stimulated podocyte apoptosis and inflammation by activating Nrf2 signaling

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Abstract

Background

The kidney is one of the most vulnerable organs during the pathogenesis of sepsis. Regulating podocyte injury may be helpful for the treatment of acute kidney injury (AKI) after sepsis. Liquiritin is a flavonoid isolated from the medicinal plant Glycyrrhizae Radix et Rhizoma (Gan-cao) and might have nephroprotective properties. The study aimed to explore the functions and mechanism of liquiritin in a cell model of septic AKI.

Methods

The cell model of septic AKI was established by stimulating podocytes with lipopolysaccharide (LPS). The concentration of proinflammatory factors (TNF-α, IL-1β and IL-6) was evaluated by enzyme-linked immunosorbent assay (ELISA). Podocyte viability and apoptosis were determined by cell counting kit-8 (CCK-8) and TdT-mediated dUTP nick-end labeling (TUNEL) assays. Western blotting was performed to measure the protein levels of apoptosis-related markers, nuclear factor E2-related factor 2 (Nrf2), cytoplasmic Nrf2, and nuclear Nrf2. RT-qPCR was required to assess the mRNA levels of Nrf2 and proinflammatory cytokines.

Results

LPS treatment induced podocyte injury by suppressing cell viability and accelerating cell apoptosis, and the trend was reversed by liquiritin. Moreover, liquiritin prevented LPS-evoked high levels of proinflammatory cytokines in podocytes. LPS caused the inactivation of the Nrf2 signaling by reducing cytoplasmic Nrf2 level and increasing nuclear Nrf2 level. Liquiritin activated the Nrf2 signaling in the context of LPS by controlling Nrf2 nuclear transition. Inhibition of Nrf2 signaling using ML385 suppressed the protective effect of liquiritin on podocyte dysfunction.

Conclusion

Liquiritin mitigates LPS-induced podocyte apoptosis and inflammation by activating Nrf2 signaling.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

The work was supported by the Natural Science Fund of Hubei Science and Technology Department, General Project (2022CFC002).

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Author notes

  1. Shijiao Zheng, Yu Li and Dan Luo contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, The 7th Hospital of Wuhan, No.6 Zhongnaner Road, Wuchang District, Wuhan, Hubei, People’s Republic of China

    Shijiao Zheng, Cairong Zhu, Haiyan Zhao, Jing He, Hongyu Yang & Tong Wang

  2. School of Medicine, Jianghan University, Wuhan, Hubei, People’s Republic of China

    Yu Li

  3. Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No.26 Shengli Street, Jiang ‘an District, Wuhan, Hubei, People’s Republic of China

    Dan Luo & Zhen Chen

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Contributions

Shijiao Zheng, Yu Li, and Dan Luo were the main designers of this study. Shijiao Zheng, Yu Li, Dan Luo, Cairong Zhu, Hongyu Yang, Tong Wang, and Zhen Chen collected and analyzed the data. Shijiao Zheng, Yu Li, Dan Luo, Haiyan Zhao, Jing He, Tong Wang, and Zhen Chen drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Tong Wang or Zhen Chen.

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Shijiao Zheng, Yu Li, Dan Luo, Cairong Zhu, Haiyan Zhao, Jing He, Hongyu Yang, Tong Wang, Zhen Chen: None.

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Zheng, S., Li, Y., Luo, D. et al. Liquiritin alleviates LPS-stimulated podocyte apoptosis and inflammation by activating Nrf2 signaling. Mol. Cell. Toxicol. (2024). https://doi.org/10.1007/s13273-024-00459-1

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