Yunvjian decoction attenuates lipopolysaccharide-induced acute lung injury by inhibiting NF-κB/NLRP3 pathway and pyroptosis
IntroductionYunvjian (YNJ) decoction, a classic traditional Chinese medicine prescription for inflammatory diseases, has demonstrated good therapeutic effects in the clinical treatment of pneumonia. The aim of this study was to clarify the effective ingredients and mechanism of action of YNJ on lipo...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1430536/full |
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| author | Fanxuan Zhang Fang Wang Lisha Zhao Leqian Wang Wenjing Li Feihua Huang Feihua Huang Nani Wang Nani Wang |
| author_facet | Fanxuan Zhang Fang Wang Lisha Zhao Leqian Wang Wenjing Li Feihua Huang Feihua Huang Nani Wang Nani Wang |
| author_sort | Fanxuan Zhang |
| collection | DOAJ |
| description | IntroductionYunvjian (YNJ) decoction, a classic traditional Chinese medicine prescription for inflammatory diseases, has demonstrated good therapeutic effects in the clinical treatment of pneumonia. The aim of this study was to clarify the effective ingredients and mechanism of action of YNJ on lipopolysaccharide (LPS)-induced acute lung injury (ALI).MethodsThe effects of YNJ were evaluated in a mouse model of LPS-induced ALI and in LPS-treated MLE-12 murine lung epithelial cells and RAW264.7 macrophages in vitro. The mechanism of action of YNJ on these model systems was studied using RNA sequencing, immunohistochemical analysis, immunoblotting, immunofluorescence, ELISA, and polymerase chain reaction assays. Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied to identify the absorbed components of YNJ.ResultsYNJ attenuated pulmonary damage in LPS-treated mice, as evidenced by reduced protein content in bronchoalveolar lavage fluid, decreased lung wet/dry weight ratio, and improved respiratory function. Analysis of pneumonia-related lung injury samples from patients in the Gene Expression Omnibus dataset GSE40012 indicated that NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis was a primary mechanism in ALI. YNJ reduced the phosphorylation of nuclear factor-kappa B (NF-κB) and decreased the expression levels of lung NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved caspase-1, and interleukin-1β levels (IL-1β) in vivo. Administration of YNJ-containing mouse serum increased cell viability and decreased malondialdehyde and reactive oxidative species contents in LPS-stimulated MLE-12 cells. YNJ-containing serum also decreased the secretion of tumor necrosis factor-α, IL-6, and IL-1β in LPS-stimulated RAW264.7 macrophages, and promoted macrophage polarization toward an M2 phenotype. A total of 23 absorbed components were identified in YNJ-containing serum. Among those, network analysis and in vitro experiments indicated that diosgenin, timosaponin BII, and mangiferin are anti-inflammatory active substances.ConclusionYNJ attenuates LPS-induced ALI in mice by inhibiting pyroptosis of lung epithelial cells and macrophages via suppression of the NF-κB/NLRP3 pathway. Our findings provide novel insights into the therapeutic effects of YNJ on ALI. |
| format | Article |
| id | doaj-art-fdd0163286da4a478dbde05cae051c41 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-fdd0163286da4a478dbde05cae051c412025-01-24T07:13:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011610.3389/fphar.2025.14305361430536Yunvjian decoction attenuates lipopolysaccharide-induced acute lung injury by inhibiting NF-κB/NLRP3 pathway and pyroptosisFanxuan Zhang0Fang Wang1Lisha Zhao2Leqian Wang3Wenjing Li4Feihua Huang5Feihua Huang6Nani Wang7Nani Wang8Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaSchool of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaTongde Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaCollege of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, ChinaSecond Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaSecond Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaTongde Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaSchool of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaTongde Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaIntroductionYunvjian (YNJ) decoction, a classic traditional Chinese medicine prescription for inflammatory diseases, has demonstrated good therapeutic effects in the clinical treatment of pneumonia. The aim of this study was to clarify the effective ingredients and mechanism of action of YNJ on lipopolysaccharide (LPS)-induced acute lung injury (ALI).MethodsThe effects of YNJ were evaluated in a mouse model of LPS-induced ALI and in LPS-treated MLE-12 murine lung epithelial cells and RAW264.7 macrophages in vitro. The mechanism of action of YNJ on these model systems was studied using RNA sequencing, immunohistochemical analysis, immunoblotting, immunofluorescence, ELISA, and polymerase chain reaction assays. Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied to identify the absorbed components of YNJ.ResultsYNJ attenuated pulmonary damage in LPS-treated mice, as evidenced by reduced protein content in bronchoalveolar lavage fluid, decreased lung wet/dry weight ratio, and improved respiratory function. Analysis of pneumonia-related lung injury samples from patients in the Gene Expression Omnibus dataset GSE40012 indicated that NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis was a primary mechanism in ALI. YNJ reduced the phosphorylation of nuclear factor-kappa B (NF-κB) and decreased the expression levels of lung NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved caspase-1, and interleukin-1β levels (IL-1β) in vivo. Administration of YNJ-containing mouse serum increased cell viability and decreased malondialdehyde and reactive oxidative species contents in LPS-stimulated MLE-12 cells. YNJ-containing serum also decreased the secretion of tumor necrosis factor-α, IL-6, and IL-1β in LPS-stimulated RAW264.7 macrophages, and promoted macrophage polarization toward an M2 phenotype. A total of 23 absorbed components were identified in YNJ-containing serum. Among those, network analysis and in vitro experiments indicated that diosgenin, timosaponin BII, and mangiferin are anti-inflammatory active substances.ConclusionYNJ attenuates LPS-induced ALI in mice by inhibiting pyroptosis of lung epithelial cells and macrophages via suppression of the NF-κB/NLRP3 pathway. Our findings provide novel insights into the therapeutic effects of YNJ on ALI.https://www.frontiersin.org/articles/10.3389/fphar.2025.1430536/fullYunvjian decoctionacute lung injuryactive ingredientsNF-κBNLRP3 |
| spellingShingle | Fanxuan Zhang Fang Wang Lisha Zhao Leqian Wang Wenjing Li Feihua Huang Feihua Huang Nani Wang Nani Wang Yunvjian decoction attenuates lipopolysaccharide-induced acute lung injury by inhibiting NF-κB/NLRP3 pathway and pyroptosis Frontiers in Pharmacology Yunvjian decoction acute lung injury active ingredients NF-κB NLRP3 |
| title | Yunvjian decoction attenuates lipopolysaccharide-induced acute lung injury by inhibiting NF-κB/NLRP3 pathway and pyroptosis |
| title_full | Yunvjian decoction attenuates lipopolysaccharide-induced acute lung injury by inhibiting NF-κB/NLRP3 pathway and pyroptosis |
| title_fullStr | Yunvjian decoction attenuates lipopolysaccharide-induced acute lung injury by inhibiting NF-κB/NLRP3 pathway and pyroptosis |
| title_full_unstemmed | Yunvjian decoction attenuates lipopolysaccharide-induced acute lung injury by inhibiting NF-κB/NLRP3 pathway and pyroptosis |
| title_short | Yunvjian decoction attenuates lipopolysaccharide-induced acute lung injury by inhibiting NF-κB/NLRP3 pathway and pyroptosis |
| title_sort | yunvjian decoction attenuates lipopolysaccharide induced acute lung injury by inhibiting nf κb nlrp3 pathway and pyroptosis |
| topic | Yunvjian decoction acute lung injury active ingredients NF-κB NLRP3 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1430536/full |
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