Therapeutic Potential of Qilianxiaopi Formula: Targeting ADAM17-Mediated Chronic Inflammation in Atrophic Gastritis
<b>Background</b>: Gastric cancer (GC) is a leading cause of mortality worldwide, particularly in China. Chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are recognized as precancerous conditions contributing to GC development. Qilianxiaopi formula (QLXP), a traditional Ch...
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MDPI AG
2025-03-01
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| Online Access: | https://www.mdpi.com/1424-8247/18/3/435 |
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| author | Sijing Du Tianxiang Wang Zhiqiang Li Ting Li Zelong Miao Yuling Chen Songbiao Zhu Wei Wei Haiteng Deng |
| author_facet | Sijing Du Tianxiang Wang Zhiqiang Li Ting Li Zelong Miao Yuling Chen Songbiao Zhu Wei Wei Haiteng Deng |
| author_sort | Sijing Du |
| collection | DOAJ |
| description | <b>Background</b>: Gastric cancer (GC) is a leading cause of mortality worldwide, particularly in China. Chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are recognized as precancerous conditions contributing to GC development. Qilianxiaopi formula (QLXP), a traditional Chinese medicine (TCM), has demonstrated significant therapeutic effects on CAG and IM; however, its underlying mechanisms remain poorly understood. <b>Methods</b>: This study utilized chromatography-mass spectrometry to identify the major compounds in QLXP. Network pharmacology was used to predict the associated targets of these components. Thermal proteome profiling (TPP) pinpointed the potential binding proteins of QLXP, which were validated by bioinformatic analyses. Bio-layer interferometry (BLI) was used to analyze the interactions between QLXP and its key target proteins, thereby determining their binding components. Molecular docking predicted the binding modes between the components and proteins. <b>Results</b>: ADAM17 was identified as a key binding protein for QLXP. Further investigation revealed that QLXP inhibits the enzymatic activity of ADAM17, thereby reducing the secretion of the pro-inflammatory cytokine TNF-α, contributing to the anti-inflammatory properties of QLXP. BLI confirmed direct and reversible binding interactions between QLXP and ADAM17. Narirutin, isolated from the ADAM17 binding fraction, displayed the highest affinity for QLXP. <b>Conclusions</b>: This study highlights ADAM17 as a key molecular target of QLXP and narirutin as its principal binding component. The integrated approach combining chromatography-mass spectrometry, network pharmacology, TPP, BLI, and molecular docking provides a robust framework for elucidating the mechanisms of action of TCM. |
| format | Article |
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| issn | 1424-8247 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-8b329a29a9ee4fb1a9359ad5bf2f9fcd2025-08-20T01:48:53ZengMDPI AGPharmaceuticals1424-82472025-03-0118343510.3390/ph18030435Therapeutic Potential of Qilianxiaopi Formula: Targeting ADAM17-Mediated Chronic Inflammation in Atrophic GastritisSijing Du0Tianxiang Wang1Zhiqiang Li2Ting Li3Zelong Miao4Yuling Chen5Songbiao Zhu6Wei Wei7Haiteng Deng8MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaChinese Institutes for Medical Research (CIMR), Beijing 100069, ChinaWangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, ChinaMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China<b>Background</b>: Gastric cancer (GC) is a leading cause of mortality worldwide, particularly in China. Chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are recognized as precancerous conditions contributing to GC development. Qilianxiaopi formula (QLXP), a traditional Chinese medicine (TCM), has demonstrated significant therapeutic effects on CAG and IM; however, its underlying mechanisms remain poorly understood. <b>Methods</b>: This study utilized chromatography-mass spectrometry to identify the major compounds in QLXP. Network pharmacology was used to predict the associated targets of these components. Thermal proteome profiling (TPP) pinpointed the potential binding proteins of QLXP, which were validated by bioinformatic analyses. Bio-layer interferometry (BLI) was used to analyze the interactions between QLXP and its key target proteins, thereby determining their binding components. Molecular docking predicted the binding modes between the components and proteins. <b>Results</b>: ADAM17 was identified as a key binding protein for QLXP. Further investigation revealed that QLXP inhibits the enzymatic activity of ADAM17, thereby reducing the secretion of the pro-inflammatory cytokine TNF-α, contributing to the anti-inflammatory properties of QLXP. BLI confirmed direct and reversible binding interactions between QLXP and ADAM17. Narirutin, isolated from the ADAM17 binding fraction, displayed the highest affinity for QLXP. <b>Conclusions</b>: This study highlights ADAM17 as a key molecular target of QLXP and narirutin as its principal binding component. The integrated approach combining chromatography-mass spectrometry, network pharmacology, TPP, BLI, and molecular docking provides a robust framework for elucidating the mechanisms of action of TCM.https://www.mdpi.com/1424-8247/18/3/435chronic atrophic gastritisQilianxiaopi formulanetwork pharmacologythermal proteome profilingbio-layer interferometryADAM17 |
| spellingShingle | Sijing Du Tianxiang Wang Zhiqiang Li Ting Li Zelong Miao Yuling Chen Songbiao Zhu Wei Wei Haiteng Deng Therapeutic Potential of Qilianxiaopi Formula: Targeting ADAM17-Mediated Chronic Inflammation in Atrophic Gastritis Pharmaceuticals chronic atrophic gastritis Qilianxiaopi formula network pharmacology thermal proteome profiling bio-layer interferometry ADAM17 |
| title | Therapeutic Potential of Qilianxiaopi Formula: Targeting ADAM17-Mediated Chronic Inflammation in Atrophic Gastritis |
| title_full | Therapeutic Potential of Qilianxiaopi Formula: Targeting ADAM17-Mediated Chronic Inflammation in Atrophic Gastritis |
| title_fullStr | Therapeutic Potential of Qilianxiaopi Formula: Targeting ADAM17-Mediated Chronic Inflammation in Atrophic Gastritis |
| title_full_unstemmed | Therapeutic Potential of Qilianxiaopi Formula: Targeting ADAM17-Mediated Chronic Inflammation in Atrophic Gastritis |
| title_short | Therapeutic Potential of Qilianxiaopi Formula: Targeting ADAM17-Mediated Chronic Inflammation in Atrophic Gastritis |
| title_sort | therapeutic potential of qilianxiaopi formula targeting adam17 mediated chronic inflammation in atrophic gastritis |
| topic | chronic atrophic gastritis Qilianxiaopi formula network pharmacology thermal proteome profiling bio-layer interferometry ADAM17 |
| url | https://www.mdpi.com/1424-8247/18/3/435 |
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