Scholarlink

Background <p>Recent studies have demonstrated the pivotal role of pathogenic Th17 cells during the target organ damage in systemic lupus erythematosus (SLE). Therefore, identifying Th17-related precision therapeutic targets is essential for developing effective treatments.</p> Methods <p>Potential targets of a novel alkaloid compound, Dehydrocorydaline (DHC), in SLE were investigated using integrated network pharmacology and molecular docking. The therapeutic efficacy of DHC was evaluated&#xa0;in vivo&#xa0;using a lupus-prone mouse model and&#xa0;in vitro&#xa0;via pathogenic Th17 polarization assays. Mechanistic studies were conducted using transcriptional analysis, cell thermal shift assay (CETSA), microscale thermophoresis (MST), and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR).</p> Results <p>This study demonstrates the therapeutic potential of DHC in SLE. Network pharmacology analysis identified mTOR signaling and Th17 cell polarization as key potential targets and pathways of DHC. In vivo, DHC treatment selectively reduced the frequencies of Th17 cells, inhibited serum IL-17A levels, restored glomerular filtration rate (GFR), and attenuated renal damage in lupus mice. Molecular docking, CETSA, and MST results suggested a direct interaction between DHC and mTOR.&#xa0;In vitro, DHC inhibited the phosphorylation of mTOR and STAT3 during pathogenic Th17 differentiation. Pharmacological activation of mTOR reversed the inhibitory effects of DHC on STAT3 activation and Th17 differentiation. Mechanistically, DHC blocked the mTOR-dependent STAT3 nuclear translocation and&#xa0;<i>Rorc</i>&#xa0;transcription during Th17 polarization.</p> Conclusion <p>DHC attenuates renal damage in SLE by suppressing the Th17 response via the mTOR/STAT3/RORγt axis. This finding represents a novel therapeutic strategy for addressing the unmet clinical needs in SLE.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dehydrocorydaline treatment suppresses Th17 differentiation via the mTOR-mediated STAT3-RORγt signaling in systemic lupus erythematosus

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月13日

查看全文
  • Jiena Liu,
  • Jingpeng Zheng,
  • Yuanhong Sun,
  • Weijie Li,
  • Huafeng Fu,
  • Jianteng Zeng,
  • Haiqi Wu,
  • Yanfang Meng,
  • Yu Liu,
  • Daiting You,
  • Yuting Cui,
  • Zhongyu Tian,
  • Junhao Hu,
  • Chun Tang,
  • Fan Xiao,
  • Ting Pan,
  • Liwei Lu,
  • Yuanye Dang,
  • Xiaoyan Dai,
  • Hongmei Tan,
  • Kongyang Ma

摘要

Background

Recent studies have demonstrated the pivotal role of pathogenic Th17 cells during the target organ damage in systemic lupus erythematosus (SLE). Therefore, identifying Th17-related precision therapeutic targets is essential for developing effective treatments.

Methods

Potential targets of a novel alkaloid compound, Dehydrocorydaline (DHC), in SLE were investigated using integrated network pharmacology and molecular docking. The therapeutic efficacy of DHC was evaluated in vivo using a lupus-prone mouse model and in vitro via pathogenic Th17 polarization assays. Mechanistic studies were conducted using transcriptional analysis, cell thermal shift assay (CETSA), microscale thermophoresis (MST), and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR).

Results

This study demonstrates the therapeutic potential of DHC in SLE. Network pharmacology analysis identified mTOR signaling and Th17 cell polarization as key potential targets and pathways of DHC. In vivo, DHC treatment selectively reduced the frequencies of Th17 cells, inhibited serum IL-17A levels, restored glomerular filtration rate (GFR), and attenuated renal damage in lupus mice. Molecular docking, CETSA, and MST results suggested a direct interaction between DHC and mTOR. In vitro, DHC inhibited the phosphorylation of mTOR and STAT3 during pathogenic Th17 differentiation. Pharmacological activation of mTOR reversed the inhibitory effects of DHC on STAT3 activation and Th17 differentiation. Mechanistically, DHC blocked the mTOR-dependent STAT3 nuclear translocation and Rorc transcription during Th17 polarization.

Conclusion

DHC attenuates renal damage in SLE by suppressing the Th17 response via the mTOR/STAT3/RORγt axis. This finding represents a novel therapeutic strategy for addressing the unmet clinical needs in SLE.

Graphical Abstract