Combining LC/IM-QTOF-MS with serum pharmacochemistry to identify active compounds and functional mechanisms of Fritillaria ussuriensis in asthma.
Fritillaria u ssuriensis 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...
| Publicado en: | Journal of Ethnopharmacology Vol. 362 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Elsevier B.V.
May2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=191887672&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 191887672 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03788741 3MS jtl: Journal of Ethnopharmacology issn: 03788741 maglogo: N pubinfo: dt: May2026 vid: 362 pid: 1004 pub: Elsevier B.V. artinfo: ui: 191887672 191887672 191887672 10.1016/j.jep.2026.121370 191887672 ppct: 1 formats: tig: atl: Combining LC/IM-QTOF-MS with serum pharmacochemistry to identify active compounds and functional mechanisms of Fritillaria ussuriensis in asthma. aug: au: Zhuang, Leixin Wang, Yue Hao, Zhichao Guan, Wei Chen, Qingshan Zhang, Lili Liu, Shu Ma, Xiaochi Naseem, Anam Kuang, Haixue Liu, Yan affil: Key Laboratory of Basic and Application Research of Beiyao, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, 150040, China sug: subj: Asthma Drug Therapy Plants, Medicinal Pharmacodynamics Plant Extracts Pharmacodynamics Liquid Chromatography-Mass Spectrometry Methods Spectrum Analysis Phytochemicals Serum Analysis Animal Studies Mice Models, Biological Mass Spectrometry In Vivo Studies In Vitro Studies Immunohistochemistry Respiratory Function Tests Staining and Labeling Benzopyrans Fluorescent Dyes Blotting, Western Fluorescent Antibody Technique Molecular Docking Simulation Intracellular Signaling Peptides and Proteins Alkaloids Network Pharmacology NF-kappa B Drug Effects Signal Transduction Drug Effects Peptide Hydrolases Ion Channels Lung Drug Effects Apoptosis Drug Effects Proteins Metabolism ab: Fritillaria u ssuriensis 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. 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. 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. 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. 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. [Display omitted] • LC/IM-QTOF-MS and multidimensional database first applied for precise ID of blood-absorbed FUM compounds. • Integrated serum pharmacochemistry, network pharmacology, and in vivo / vitro experiments to elucidate anti-asthma mechanisms. • FUM alleviates asthma airway hyperresponsiveness, inflammation, and epithelial pyroptosis via inhibiting PI3K/AKT/NF‑κB and NLRP3/Caspase‑1/GSDMD axes. • Demonstrated strong binding between peiminine and mTOR via molecular docking, dynamics simulation, and CETSA assays. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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