Sanhuang Xiexin decoction ameliorates acute lung injury by disrupting NEK7-NLRP3 inflammasome activation

  • J Ethnopharmacol. 2026 Jul 15:366:121624. doi: 10.1016/j.jep.2026.121624.
Shun Wang  1 ,  Biao Lei  2 ,  Lu Qi  3 ,  Tao Guo  1 ,  Zhuocao Qi  1 ,  Suwan Wu  1 ,  Zhiqiang Yan  4 ,  Dan Gao  1 ,  Liangbo Jiao  1 ,  Jiayun Wang  1 ,  Zhongju Xu  5 ,  Bo Tan  6 ,  Aidong Yang  7
Affiliations
  • 1. The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 2. Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, 510315, China.
  • 3. The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; The First College of Clinical Medical Science, China Three Gorges University &Yichang Central People's Hospital, Yichang, 443003, China.
  • 4. Clinical Pharmacokinetic Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 5. Department of Traditional Chinese Medicine, Gongli Hospital of Shanghai Pudong New Area, Shanghai, 200135, China.
  • 6. Clinical Pharmacokinetic Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: [email protected].
  • 7. The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: [email protected].
PMID: 41935649 DOI: 10.1016/j.jep.2026.121624
Abstract

Ethnopharmacological relevance: Acute lung injury (ALI) is a life-threatening condition with high mortality and limited treatment options. While Sanhuang Xiexin Decoction (SHXXD) has shown clinical potential in treating ALI, its molecular mechanism remains incompletely understood.

Aim of the study: This study investigates whether SHXXD alleviates ALI by targeting the NEK7-NLRP3 axis, thereby inhibiting inflammasome activation and Pyroptosis.

Materials and methods: The chemical constituents and blood-absorbed components of SHXXD were characterized by UPLC-Q-TOF-MS. Its protective effects were evaluated both in vivo and in vitro. Network pharmacology and transcriptomics were integrated to identify key pathways. Co-immunoprecipitation (Co-IP), Western blotting, and immunofluorescence were used to assess NEK7-NLRP3 inflammasome assembly and Pyroptosis. Molecular docking, molecular dynamics simulations, cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR) were employed to evaluate the binding of SHXXD constituents to NEK7.

Results: A total of 61 compounds were identified in SHXXD, with 17 prototypes and 77 metabolites detected in circulation. SHXXD markedly attenuated pulmonary inflammation and suppressed NLRP3 inflammasome-driven Pyroptosis in vivo and in vitro. Co-IP showed that SHXXD impaired the interaction between NEK7 and NLRP3. Among the blood-absorbed constituents, wogonoside was identified as a NEK7-binding component and showed stable interaction with NEK7, as supported by docking, CETSA, and SPR.

Conclusion: SHXXD exerts protective effects against ALI by disrupting the NEK7-NLRP3 interaction, which subsequently inhibits inflammasome assembly and Pyroptosis. Wogonoside may contribute to this mechanism, although the overall therapeutic efficacy likely results from multi-component synergism.

Keywords
Acute lung injury; NEK7; NLRP3 inflammasome; Pyroptosis; Sanhuang Xiexin decoction; Wogonoside.
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