Physalin H ameliorates LPS-induced acute lung injury via KEAP1/ NRF2 axis

被引：5

作者：

Cai, Yuxing ^{[1
]}

Zhu, Jiangmin ^{[1
]}

Zhu, Ling ^{[1
]}

Hong, Lihong ^{[1
]}

Zhang, Jianfei ^{[1
]}

Kong, Lingyi ^{[1
]}

Chen, Chen ^{[1
]}

Luo, Jianguang ^{[1
]}

机构：

[1] China Pharmaceut Univ, Sch Tradit Chinese Pharm, Jiangsu Key Lab Bioact Nat Prod Res, Nanjing, Jiangsu, Peoples R China

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2024年 / 131卷

基金：

中国国家自然科学基金;

关键词：

Physalin H; Withanolide; Redox system; Acute lung injury; NRF2; activator; OXIDATIVE STRESS; PATHOGENESIS; INFLAMMATION;

D O I：

10.1016/j.intimp.2024.111789

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Physalin H (PH), a withanolide isolated from Physalis angulata L. has been reported to have anti-inflammatory effect. However, its impact on acute lung injury (ALI) remains unexplored. In this study, we observed that PH significantly alleviated inflammation in LPS-stimulated macrophages by suppressing the release of proinflammatory cytokines (TNF- alpha, IL -18, and IL -6) and down -regulating the expression of the inflammation -related genes. RNA sequencing analysis revealed a significant up -regulation of the NRF2 pathway by PH. Further investigation elucidated that PH attenuated the ubiquitination of NRF2 by impeding the interaction between NRF2 and KEAP1, thereby facilitating NRF2 nuclear translocation and up -regulating the expression of target genes. Consequently, it regulated redox system and exerted anti-inflammatory effect. Consistently, PH also significantly alleviated pathological damage and inflammation in LPS-induced ALI mice model, which could be reversed by administration of an NRF2 inhibitor. Collectively, these results suggest that PH ameliorates ALI by activating the KEAP1/NRF2 pathway. These findings provide a foundation for further development of pH as a new anti-inflammatory agent for ALI therapy.

引用

页数：11

共 48 条

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