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Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets

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Abstract

Kidney is a major target organ in both antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis (APSN-LN) is intricate and remains largely unrevealed. We proposed in present work, that generation of antiphospholipid antibodies (aPLs), especially those directed towards the oxidized neoepitopes, are largely linked with the redox status along with disease progression. Moreover, we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZW×BXSB F1 mice suffered from APSN-LN. SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties. In current study, we elaborated the therapeutic benefits of SM934 in male NZW×BXSB F1 mice, a murine model develops syndrome resembled human APS associated with SLE, for the first time. SM934 treatment comprehensively impeded autoantibodies production, inflammatory cytokine accumulation and excessive oxidative stress in kidney. Among others, we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets. Collectively, our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81903882 and 81871240), the National Science and Technology Major Project “New Drug Creation and Manufacturing Program” (2018ZX09711002-014-001), the Personalized Medicines—“Molecular Signature-based Drug Discovery and Development”, Strategic Priority Research Program of the Chinese Academy of Sciences (XDA12020107 and XDA12020369).

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Authors and Affiliations

  1. Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Zemin Lin, Yuting Liu, Li Chen, Shiqi Cao, Xiaoqian Yang, Fenghua Zhu, Wei Tang, Shijun He & Jianping Zuo

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Yuting Liu, Li Chen, Shiqi Cao, Wei Tang, Shijun He & Jianping Zuo

  3. Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Yueteng Huang & Jianping Zuo

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  1. Zemin Lin
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  3. Li Chen
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Correspondence to Shijun He or Jianping Zuo.

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Lin, Z., Liu, Y., Chen, L. et al. Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets. Sci. China Life Sci. 64, 1702–1719 (2021). https://doi.org/10.1007/s11427-020-1840-1

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