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. 2021 Mar;178(5):1182-1199.
doi: 10.1111/bph.15364.

Nuciferine protects against folic acid-induced acute kidney injury by inhibiting ferroptosis

Danyu Li  1 , Bing Liu  1 , Yumei Fan  1 , Ming Liu  1 , Bihui Han  1 , Yanxiu Meng  1 , Xiao Xu  1 , Zhiyuan Song  2 , Xiaopeng Liu  1   3 , Qiang Hao  1 , Xianglin Duan  1 , Akira Nakai  4 , Yanzhong Chang  1 , Pengxiu Cao  1 , Ke Tan  1
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Free article

Nuciferine protects against folic acid-induced acute kidney injury by inhibiting ferroptosis

Danyu Li et al. Br J Pharmacol. 2021 Mar.
Free article

Erratum in

  • CORRECTION.
    [No authors listed] [No authors listed] Br J Pharmacol. 2022 May;179(10):2313-2317. doi: 10.1111/bph.15829. Br J Pharmacol. 2022. PMID: 35383916 No abstract available.

Abstract

Background and purpose: Acute kidney injury is a common clinical problem with no definitive or specific treatment. Therefore, the molecular mechanisms of acute kidney injury must be fully understood to develop novel treatments. Nuciferine, a major bioactive compound isolated from the lotus leaf, possesses extensive pharmacological activities. Its effect on folic acid-induced acute kidney injury, however, remains unknown. Here, we aimed to clarify the pharmacological effects of nuciferine and its mechanisms of action in acute kidney injury.

Experimental approach: The effects of nuciferine on folic acid-induced acute kidney injury in mice were investigated. HK-2 human proximal tubular epithelial cells and HEK293T HEK cells were used to evaluate the protective effect of nuciferine on RSL3-induced ferroptosis.

Key results: Nuciferine treatment mitigated the pathological alterations, ameliorated inflammatory cell infiltration and improved kidney dysfunction in mice with folic acid-induced acute kidney injury. In HK-2 and HEK293T cells, nuciferine significantly prevented RSL3-induced ferroptotic cell death. Mechanistically, nuciferine significantly inhibited ferroptosis by preventing iron accumulation and lipid peroxidation in vitro and in vivo. Moreover, knockdown of glutathione (GSH) peroxidase 4 (GPX4) abolished the protective effect of nuciferine against ferroptosis.

Conclusion and implications: Nuciferine ameliorated renal injury in mice with acute kidney injury, perhaps by inhibiting the ferroptosis. Nuciferine may represent a novel treatment that improves recovery from acute kidney injury by targeting ferroptosis.

Keywords: GPX4; RSL3; acute kidney injury; ferroptosis; nuciferine.

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References

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