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

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.

• Authors: Zemin Lin, Yuting Liu, Li Chen, Shiqi Cao, Yueteng Huang, Xiaoqian Yang, Fenghua Zhu, Wei Tang, Shijun He, Jianping Zuo
• Journal: Science China. Life sciences (Sci China Life Sci) Vol. 64 Issue 10 Pg. 1702-1719 (Oct 2021) ISSN: 1869-1889 [Electronic] China
• PMID: 33481164 (Publication Type: Journal Article)
• Copyright: © 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Antiphospholipid
• Artemisinins
• Cytokines
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Reactive Oxygen Species
• beta-aminoarteether maleate

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Antibodies, Antiphospholipid (metabolism)
• Antiphospholipid Syndrome (drug therapy, metabolism)
• Artemisinins (therapeutic use)
• Cytokines (metabolism)
• Disease Models, Animal
• Inflammation
• Kidney (drug effects, metabolism)
• Lupus Erythematosus, Systemic (drug therapy, metabolism)
• Lupus Nephritis (metabolism, prevention & control)
• Male
• Mice
• NF-E2-Related Factor 2 (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)