2. Academic Validation
  3. Combining LC/IM-QTOF-MS with serum pharmacochemistry to identify active compounds and functional mechanisms of Fritillaria ussuriensis in asthma

Combining LC/IM-QTOF-MS with serum pharmacochemistry to identify active compounds and functional mechanisms of Fritillaria ussuriensis in asthma

  • J Ethnopharmacol. 2026 May 10:362:121370. doi: 10.1016/j.jep.2026.121370.
Leixin Zhuang 1,  Yue Wang 2,  Zhichao Hao 3,  Wei Guan 4,  Qingshan Chen 5,  Lili Zhang 6,  Shu Liu 7,  Xiaochi Ma 8,  Anam Naseem 9,  Haixue Kuang 10,  Yan Liu 11
Affiliations

Affiliations

  • 1 Key Laboratory of Basic and Application Research of Beiyao, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, 150040, China; Traditional Chinese medicine biological genetics, Heilongjiang province double first-class construction interdiscipline, Harbin, 150040, China. Electronic address: [email protected].
  • 2 Key Laboratory of Basic and Application Research of Beiyao, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, 150040, China; Traditional Chinese medicine biological genetics, Heilongjiang province double first-class construction interdiscipline, Harbin, 150040, China. Electronic address: [email protected].
  • 3 Key Laboratory of Basic and Application Research of Beiyao, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, 150040, China; Traditional Chinese medicine biological genetics, Heilongjiang province double first-class construction interdiscipline, Harbin, 150040, China. Electronic address: [email protected].
  • 4 Key Laboratory of Basic and Application Research of Beiyao, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, 150040, China; Traditional Chinese medicine biological genetics, Heilongjiang province double first-class construction interdiscipline, Harbin, 150040, China. Electronic address: [email protected].
  • 5 College of Agriculture, Northeast Agricultural University, Harbin, 150030, China. Electronic address: [email protected].
  • 6 College of Agriculture, Northeast Agricultural University, Harbin, 150030, China. Electronic address: [email protected].
  • 7 State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China. Electronic address: [email protected].
  • 8 Second Affiliated Hospital, Dalian Medical University, Dalian, 116023, China. Electronic address: [email protected].
  • 9 Key Laboratory of Basic and Application Research of Beiyao, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, 150040, China; Traditional Chinese medicine biological genetics, Heilongjiang province double first-class construction interdiscipline, Harbin, 150040, China. Electronic address: [email protected].
  • 10 Key Laboratory of Basic and Application Research of Beiyao, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, 150040, China; Traditional Chinese medicine biological genetics, Heilongjiang province double first-class construction interdiscipline, Harbin, 150040, China. Electronic address: [email protected].
  • 11 Key Laboratory of Basic and Application Research of Beiyao, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, 150040, China; Traditional Chinese medicine biological genetics, Heilongjiang province double first-class construction interdiscipline, Harbin, 150040, China. Electronic address: [email protected].
PMID: 41687937 DOI: 10.1016/j.jep.2026.121370
Abstract

Ethnopharmacological relevance: Fritillaria ussuriensis Maxim. (FUM) is a traditional medicinal plant widely used in Asian countries, renowned for its effects of clearing heat, moistening the lungs, resolving phlegm, relieving cough, and alleviating asthma. In traditional medicinal practice, FUM is often used in combination with herbs such as Ephedra and Apricot Kernel. Among various preparation forms, decoction is the most common, and its traditional application methods hold significant reference value. Despite its extensive clinical application, the specific active components of FUM and its underlying mechanisms in treating asthma remain incompletely understood.

Aim of the study: To evaluate the therapeutic effects of FUM extract, this study established an OVA-induced mouse asthma model in vivo. Additionally, an in vitro Pyroptosis model was constructed by stimulating BEAS-2B cells with LPS and ATP.

Materials and methods: This study established an in vivo mouse asthma model induced by OVA and constructed an in vitro cell Pyroptosis model by stimulating BEAS-2B cells with LPS and ATP to evaluate the therapeutic effects of FUM extract. The prototype components of FUM absorbed into the bloodstream after administration were identified using liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (LC/IM-QTOF-MS) combined with serum pharmacochemistry. Network pharmacology was employed to predict potential targets and pathways of the active components. The effects on relevant protein expression in both in vivo and in vitro models were validated through behavioral observation, pulmonary function testing, HE staining, immunohistochemistry, Western blotting, and immunofluorescence techniques. Molecular docking, molecular dynamics simulations, and cellular thermal shift assays were employed to predict or validate the interactions between key active components and core targets.

Results: FUM extract significantly alleviated symptoms in OVA-induced asthmatic mice. LC/IM-QTOF-MS analysis identified nine prototype components of FUM absorbed into the bloodstream, mainly steroidal Alkaloids. Through network pharmacology and experimental validation, FUM was found to inhibit the activation of the PI3K/Akt/NF-κB pathway in both mouse lung tissue and stimulated cells, while downregulating pyroptosis-related proteins (NLRP3, GSDMD, Caspase-1). Further molecular docking and validation experiments identified peiminine as the key active component, which demonstrated stable binding with the mTOR target.

Conclusion: This study investigated the active components and potential mechanisms of FUM in asthma using serum pharmacochemistry and systems pharmacology approaches. The novel findings reveal that FUM alleviates cellular Pyroptosis and inflammatory responses by inhibiting the NLRP3 inflammasome, thereby exerting its therapeutic effects on asthma.

Keywords

Asthma; Fritillaria ussuriensis; NLRP3 inflammasome; Network pharmacology; Serum pharmacology.

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