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Obtusifolin inhibits podocyte apoptosis by inactivating NF-κB signaling in acute kidney injury

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Abstract

Acute kidney injury (AKI) is a common clinical condition and is associated with unacceptable morbidity and mortality. Obtusifolin is an anthraquinone extracted from the seeds of Cassia obtusifolia with anti-inflammatory properties. This study focused on the role and mechanism of obtusifolin in AKI. The mouse podocyte cell line MPC5 was exposed to lipopolysaccharide (LPS) to establish a cell model of AKI. The viability of MPC5 cells treated with obtusifolin and/or LPS was detected by 3-(4, 5-Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide assay. Cell apoptosis was analyzed by flow cytometry. The levels of podocyte injury- and apoptosis-related proteins as well as the nuclear factor-kappaB (NF-κB) signaling pathway was examined using western blotting analysis. The renal protective effects of obtusifolin were determined using an LPS-induced mouse model of AKI. Serum creatinine and blood urea nitrogen levels were measured. Hematoxylin–eosin staining of kidney sections was performed to evaluate renal histology. We found that MPC5 cells treated with LPS showed suppressed cell viability (p < 0.01) and increased cell apoptosis (p < 0.001). LPS reduced the protein expression of Bcl-2, nephrin, and synaptopodin as well as increased the protein levels of Bax and Cleaved Caspase-3 in podocytes in a concentration-dependent manner (p < 0.01). In addition, 10 μg/ml LPS-repressed cell viability was rescued by obtusifolin in a concentration-dependent manner (p < 0.01). Moreover, LPS-induced increase in MPC5 cell apoptosis was reversed by obtusifolin treatment (p < 0.01). Obtusifolin administration ameliorated LPS-induced kidney injury and reduced blood urea nitrogen and serum creatinine levels in mice (p < 0.001). Additionally, obtusifolin inhibited LPS-induced activation of NF-κB signaling in vitro and in vivo (p < 0.01). Overall, obtusifolin was effective in protecting renal function against LPS-induced AKI via inactivation of NF-κB signaling, which suggested that obtusifolin may act as a valuable agent for AKI therapy.

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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

The authors appreciate all the participants providing supports for this study.

Funding

This work was supported by Young Talents Project of Health Commission of Hubei Province (wj2019H151).

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Authors and Affiliations

  1. Department of Nephrology, Wuhan Sixth Hospital, Affiliated Hospital of Jianghan University, No.168, Jiang ’an District, Wuhan, Hubei, China

    Haiyan **ang, Yan Wu, Yun Zhang, Yuanhao Hong & Yaling Xu

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  1. Haiyan **ang
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  2. Yan Wu
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  3. Yun Zhang
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  4. Yuanhao Hong
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  5. Yaling Xu
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Contributions

Haiyan **ang was the main designer of this study. Haiyan **ang, Yan Wu, Yun Zhang and Yuanhao Hong performed the experiments and analyzed the data. Haiyan **ang, Yan Wu and Yaling Xu drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Haiyan **ang.

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All protocols involving animals were reviewed and approved by the Ethics Committee of Wuhan Sixth Hospital, Affiliated Hospital of Jianghan University.

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**ang, H., Wu, Y., Zhang, Y. et al. Obtusifolin inhibits podocyte apoptosis by inactivating NF-κB signaling in acute kidney injury. Cytotechnology (2024). https://doi.org/10.1007/s10616-024-00638-x

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