Exploring the Underlying Mechanism of Weiling Decoction Alleviates Cold-Dampness Diarrhea Based on Network Pharmacology, Transcriptomics, Molecular Docking and Experimental Validation
<b>Background</b>: Cold-dampness diarrhea (CDD) is a common gastrointestinal disorder in children, characterized by diarrhea and intestinal barrier dysfunction. Weiling decoction (WLD) is frequently used in clinical practice to treat CDD, a condition triggered by multiple factors. Howeve...
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2025-01-01
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| author | Yannan Zhang Shuai Zhang Yimeng Fan Sijuan Huang Shimin Wang Zhihui Hao Jianzhong Shen |
| author_facet | Yannan Zhang Shuai Zhang Yimeng Fan Sijuan Huang Shimin Wang Zhihui Hao Jianzhong Shen |
| author_sort | Yannan Zhang |
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| description | <b>Background</b>: Cold-dampness diarrhea (CDD) is a common gastrointestinal disorder in children, characterized by diarrhea and intestinal barrier dysfunction. Weiling decoction (WLD) is frequently used in clinical practice to treat CDD, a condition triggered by multiple factors. However, the molecular mechanisms underlying its therapeutic effects remain poorly understood. <b>Objectives</b>: This study aimed to evaluate the efficacy of WLD in treating CDD and to elucidate its potential mechanisms. <b>Methods</b>: UPLC-HRMS/MS was employed to identify the chemical constituents of WLD and the absorption components in the plasma of WLD-treated rats. Additionally, a rat model of CDD was established to assess the therapeutic effects of WLD through a comprehensive approach. To elucidate the molecular mechanisms underlying these effects, network pharmacology and transcriptomic analyses were performed to identify potential signaling pathways associated with CDD alleviation. Molecular docking and flow cytometry assays were subsequently utilized to validate the identified signaling pathways. <b>Results</b>: A total of 223 chemical components were detected in WLD, and 49 absorption components were identified in the plasma of WLD-treated rats by UPLC-HRMS/MS. WLD treatment significantly alleviated the symptoms of CDD, reduced intestinal damage, and diminished the inflammatory response. Additionally, WLD influenced key genes in immune-related pathways. Molecular docking revealed strong binding affinities between the main components of WLD and key targets within these pathways. Flow cytometry, along with the analysis of inflammatory cytokines and transcription factors, demonstrated that WLD modulated the balance between Th1/Th2 and Th17/Treg cell populations. <b>Conclusions</b>: This study provides the first evidence that WLD alleviates CDD by regulating the balance between Th1/Th2 and Th17/Treg cell populations. These findings offer a theoretical basis for future investigations into the therapeutic potential of WLD in the treatment of CDD. |
| format | Article |
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| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-2c210423d32a46b185be32cfaa3da7fe2025-01-24T13:45:25ZengMDPI AGPharmaceuticals1424-82472025-01-0118110910.3390/ph18010109Exploring the Underlying Mechanism of Weiling Decoction Alleviates Cold-Dampness Diarrhea Based on Network Pharmacology, Transcriptomics, Molecular Docking and Experimental ValidationYannan Zhang0Shuai Zhang1Yimeng Fan2Sijuan Huang3Shimin Wang4Zhihui Hao5Jianzhong Shen6National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaNational Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaNational Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaNational Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaCollege of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, ChinaNational Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaNational Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China<b>Background</b>: Cold-dampness diarrhea (CDD) is a common gastrointestinal disorder in children, characterized by diarrhea and intestinal barrier dysfunction. Weiling decoction (WLD) is frequently used in clinical practice to treat CDD, a condition triggered by multiple factors. However, the molecular mechanisms underlying its therapeutic effects remain poorly understood. <b>Objectives</b>: This study aimed to evaluate the efficacy of WLD in treating CDD and to elucidate its potential mechanisms. <b>Methods</b>: UPLC-HRMS/MS was employed to identify the chemical constituents of WLD and the absorption components in the plasma of WLD-treated rats. Additionally, a rat model of CDD was established to assess the therapeutic effects of WLD through a comprehensive approach. To elucidate the molecular mechanisms underlying these effects, network pharmacology and transcriptomic analyses were performed to identify potential signaling pathways associated with CDD alleviation. Molecular docking and flow cytometry assays were subsequently utilized to validate the identified signaling pathways. <b>Results</b>: A total of 223 chemical components were detected in WLD, and 49 absorption components were identified in the plasma of WLD-treated rats by UPLC-HRMS/MS. WLD treatment significantly alleviated the symptoms of CDD, reduced intestinal damage, and diminished the inflammatory response. Additionally, WLD influenced key genes in immune-related pathways. Molecular docking revealed strong binding affinities between the main components of WLD and key targets within these pathways. Flow cytometry, along with the analysis of inflammatory cytokines and transcription factors, demonstrated that WLD modulated the balance between Th1/Th2 and Th17/Treg cell populations. <b>Conclusions</b>: This study provides the first evidence that WLD alleviates CDD by regulating the balance between Th1/Th2 and Th17/Treg cell populations. These findings offer a theoretical basis for future investigations into the therapeutic potential of WLD in the treatment of CDD.https://www.mdpi.com/1424-8247/18/1/109weiling decoction (WLD)cold-dampness diarrhea (CDD)Traditional Chinese MedicineCD4+ T-cell balancegut barrier |
| spellingShingle | Yannan Zhang Shuai Zhang Yimeng Fan Sijuan Huang Shimin Wang Zhihui Hao Jianzhong Shen Exploring the Underlying Mechanism of Weiling Decoction Alleviates Cold-Dampness Diarrhea Based on Network Pharmacology, Transcriptomics, Molecular Docking and Experimental Validation Pharmaceuticals weiling decoction (WLD) cold-dampness diarrhea (CDD) Traditional Chinese Medicine CD4+ T-cell balance gut barrier |
| title | Exploring the Underlying Mechanism of Weiling Decoction Alleviates Cold-Dampness Diarrhea Based on Network Pharmacology, Transcriptomics, Molecular Docking and Experimental Validation |
| title_full | Exploring the Underlying Mechanism of Weiling Decoction Alleviates Cold-Dampness Diarrhea Based on Network Pharmacology, Transcriptomics, Molecular Docking and Experimental Validation |
| title_fullStr | Exploring the Underlying Mechanism of Weiling Decoction Alleviates Cold-Dampness Diarrhea Based on Network Pharmacology, Transcriptomics, Molecular Docking and Experimental Validation |
| title_full_unstemmed | Exploring the Underlying Mechanism of Weiling Decoction Alleviates Cold-Dampness Diarrhea Based on Network Pharmacology, Transcriptomics, Molecular Docking and Experimental Validation |
| title_short | Exploring the Underlying Mechanism of Weiling Decoction Alleviates Cold-Dampness Diarrhea Based on Network Pharmacology, Transcriptomics, Molecular Docking and Experimental Validation |
| title_sort | exploring the underlying mechanism of weiling decoction alleviates cold dampness diarrhea based on network pharmacology transcriptomics molecular docking and experimental validation |
| topic | weiling decoction (WLD) cold-dampness diarrhea (CDD) Traditional Chinese Medicine CD4+ T-cell balance gut barrier |
| url | https://www.mdpi.com/1424-8247/18/1/109 |
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