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| Efficacy and mechanism of action of Fuzheng Touxie Jiedu Prescription in modulating NLRP3/Caspase-1/GSDMD pathways in rats with pneumonia caused by multi-drug resistant organisms |
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| DOI
10.11656/j.issn.1672-1519.2026.08.10 |
| Key Words
pneumonia caused by multi-drug resistant organisms;Fuzheng Touxie Jiedu Prescription;NLRP3/Caspase-1/GSDMD signaling pathway;LC-Q-TOF-MS;network pharmacology |
| Author Name | Affiliation | E-mail | | LIU Yanbin | Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China | | | ZHU Rui | Yuquan Hospital, Tsinghua University, Beijing 100040, China | | | WU Caijun | Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
Institute of Sepsis, Beijing University of Chinese Medicine, Beijing 100700, China | | | YAN Jun | The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing 100029, China
Institute of Sepsis, Beijing University of Chinese Medicine, Beijing 100700, China | dzmyyyj@126.com |
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| Abstract
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| Objective To explore the pharmacodynamic effects and mechanisms of Fuzheng Touxie Jiedu Prescription on rats with pneumonia caused by multi-drug resistant organisms based on liquid chromatography-quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS), network pharmacology, molecular docking, and animal experiments. Methods A rat model of pneumonia caused by multi-drug resistant Pseudomonas aeruginosa was established via tracheal instillation. Thirty rats were randomly divided into 5 groups: blank control group, model group, traditional Chinese medicine (TCM) group (Fuzheng Touxie Jiedu Prescription), Western medicine group, and integrated Chinese-Western medicine group. Additionally, another 6 rats were divided into the normal group and the drug-administered group for the preparation of drug-containing serum. LC-Q-TOF-MS was used for chemical analysis of drug-containing serum. Network pharmacology predicted the active components, core targets, and signaling pathways of the prescription. Molecular docking was performed using the CB-Dock2 platform. Hematoxylin and eosin (HE) staining assessed lung tissue pathology. ELISA was used to detect the expression olevels of interleukin (IL) -18, IL-1β, tumor necrosis factor (TNF) -α, and IL-6 in rat serum. Quantitative real-time PCR (qPCR) and Western blot measured mRNA and protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), Caspase-1, and gasdermin D (GSDMD) in rat lung tissue. Results Thirty-four active components were identified. Analysis revealed 176 intersecting targets related to both the disease and the prescription, including 38 core targets (NFKB1, TNF, IL6, AKT1, etc.). Core active components included 7-Hydroxycoumarin, Salvianono, Quercetin, Liquiritin, etc. Key signaling pathway involved MAPK, PI3K-Akt, FoxO signaling pathways, primaily related to inflammation and immunity. Molecular docking demonstrated strong binding activity between key components and core targets. Animal experiments showed that the Fuzheng Touxie Jiedu Prescription alleviated pathological lung tissue damage, and inhibited the expressions of inflammatory factors including IL-18, IL-1β, TNF-α, and IL-6 in serum, downregulated mRNA and protein expression of NLRP3, ASC, Caspase-1, and GSDMD in lung tissue. Conclusion The Fuzheng Touxie Jiedu Prescription exhibits therapeutic effects against multi-drug resistant organisms pneumonia in rats. Its mechanisms likely involves regulating the NLRP3/Caspase-1/GSDMD signaling pathway to inhibit excessive inflammation and immune responses. |
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