2. Academic Validation
  3. Steroid constituents of Solidago canadensis alleviate LPS-induced inflammation via AMPK regulated mitophagy/NLRP3 and NF-κB pathway

Steroid constituents of Solidago canadensis alleviate LPS-induced inflammation via AMPK regulated mitophagy/NLRP3 and NF-κB pathway

  • Eur J Pharmacol. 2025 Jul 5:998:177512. doi: 10.1016/j.ejphar.2025.177512.
Wenying Yin 1,  Han Xue 2,  Yongqi Zhang 3,  Rongxian Li 4,  Mengjia Liu 5,  Hongwei Yue 6,  Di Ge 7,  Na Liu 8
Affiliations

Affiliations

  • 1 School of Biological Science and Technology, University of Jinan, Jinan, 250024, China. Electronic address: 1920591437@qq.com.
  • 2 School of Biological Science and Technology, University of Jinan, Jinan, 250024, China. Electronic address: 844665470@qq.com.
  • 3 School of Biological Science and Technology, University of Jinan, Jinan, 250024, China. Electronic address: 2535655446@qq.com.
  • 4 School of Biological Science and Technology, University of Jinan, Jinan, 250024, China. Electronic address: 1908044288@qq.com.
  • 5 School of Biological Science and Technology, University of Jinan, Jinan, 250024, China. Electronic address: 1603608067@qq.com.
  • 6 Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China. Electronic address: talatala@126.com.
  • 7 School of Biological Science and Technology, University of Jinan, Jinan, 250024, China. Electronic address: bio_ged@ujn.edu.cn.
  • 8 School of Biological Science and Technology, University of Jinan, Jinan, 250024, China. Electronic address: mls_liun@ujn.edu.cn.
PMID: 40113066 DOI: 10.1016/j.ejphar.2025.177512
Abstract

Inflammation is a major risk factor for a variety of human diseases, such as sepsis, Inflammatory Bowel Disease (IBD) and also major Cardiovascular Disease including atherosclerosis. Solidago canadensis is used as a traditional medicine to treat inflammation-related diseases. However, the component with anti-inflammatory activity of Solidago canadensis is not clear. In this study, we aimed to search for new bioactive Steroids from Solidago canadensis and investigate their anti-inflammatory activity both in vitro and in vivo. Lipopolysaccharides (LPS)-stimulated RAW264.7 cells, mouse bone marrow-derived macrophages (BMDMs) and peripheral blood mononuclear cells (PBMCs) were used to induce an inflammation response. Compound 10 outperformed Other compounds for superior anti-inflammatory activity and significant inhibition of NLR family, pyrin domain containing 3 (NLRP3) inflammasome activation. Mechanistically, compound 10 induced Mitophagy by activating AMP-activated protein kinas (AMPK) to suppress NLRP3 inflammasome activation. Inhibiting AMPK by inhibitor BML-275 significantly attenuated compound 10 induced Mitophagy and subsequent the NLRP3 inflammasome. Besides, the NF-κB activation, key step in NLRP3 inflammasome priming, was also suppressed by compound 10 via activation of AMPK. In addition, the in vivo experiments showed that compound 10 could alleviate LPS-induced inflammatory and dextran sulfate sodium salt -induced colitis in C57BL/6 mice. Collectively, the present study, for the first time, shows that the Steroids compound 10 exhibited anti-inflammatory effect via AMPK/Mitophagy/NLRP3 as well as AMPK/NF-κB/NLRP3 signaling pathway, which strongly suggests the therapeutic potential of compound 10 in various inflammatory diseases.

Keywords

AMPK; Mitophagy; NLRP3 inflammasome; RAW264.7 cells; Solidago canadensis.

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