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傳統中醫與現代醫學的橋樑： 利用化學分子網絡揭示寒熱藥性
Other Title
Bridging traditional Chinese medicine and modern medical science: Unveiling cold-hot properties using chemical molecular networking approach
Type
thesis
Date Issued
2025-06-17
Author(s)
Le, Huong Giang
Advisor
Subjects
系所名稱：中草藥臨床藥物研發博士學位學程
Publisher
中草藥臨床藥物研發博士學位學程
Description
學位別：博士
口試委員：賴奎宏; 黃聰龍; 王靜瓊; 李慶國; 蘇俊翰
關鍵字：cold-hot properties、inflammation、interleukin 6、molecular networking、molecular docking、moleuclar dynamics、network pharmacology
口試委員：賴奎宏; 黃聰龍; 王靜瓊; 李慶國; 蘇俊翰
關鍵字：cold-hot properties、inflammation、interleukin 6、molecular networking、molecular docking、moleuclar dynamics、network pharmacology
Abstract
Objective: This thesis aims to validate the theoretical foundations of Traditional Chinese Medicine (TCM) concerning cold-hot properties, establishing a scientific basis for their application in modern medicine. It hypothesizes that hot-natured TCMs are linked to circulatory disorders, while cold-natured, heat-clearing TCMs are associated with anti-inflammatory effects. Through advanced molecular networking and pharmacological analysis, the research seeks to elucidate the biochemical mechanisms underlying these traditional classifications.
Methods: A systematic review and data mining approach was employed to correlate hot-natured TCMs with cardiovascular conditions and cold-natured TCMs with inflammatory diseases. Key compounds within cold-natured herbs were identified using LC-QTOF-MS/MS and analyzed through GNPS molecular networking. Target prediction was conducted using SwissTargetPrediction and ETCM, while inflammation-related targets were curated from OMIM, GeneCards, and DisGeNet. A PPI network was constructed in Cytoscape, and compound-disease overlaps were analyzed via GO and KEGG enrichment. Molecular docking and dynamics simulations were performed to confirm compound-target interactions.
Results: A total of 95 hot-natured herbs were found to contain 36 terpenoids associated with four major circulatory disorders. Additionally, 16 metabolites derived from Panax species exhibited potential anti-fatigue and cardiovascular benefits. Analysis of 79 heat-clearing herbs identified 50 flavonoid-O-glycosides with notable anti-inflammatory activity. Molecular profiling of 17 representative herbs revealed 418 distinct compounds, which were mapped to 1,380 compound-related and 895 disease-associated targets, yielding 255 overlapping targets. IL6 was identified as a central inflammatory node, with key enriched pathways including EGFR tyrosine kinase inhibitor resistance, PD-L1/PD-1 immune checkpoint regulation, and AGE-RAGE signaling. Molecular docking and dynamics simulations confirmed stable binding interactions, particularly involving IL6 residues PHE74, LEU178, and ARG179.
Conclusion: This study offers substantive evidence for the biochemical underpinnings of TCM’s cold-hot classification, revealing distinct molecular signatures aligned with their therapeutic roles. Hot-natured herbs were enriched in terpenoids associated with circulatory conditions, while cold-natured, heat-clearing herbs contained flavonoid-O-glycosides targeting inflammatory pathways, notably via IL6 modulation. The integration of metabolomics, molecular networking, and systems pharmacology provides a robust framework for elucidating TCM mechanisms, supporting its scientific validation and translational relevance in modern drug discovery.
Methods: A systematic review and data mining approach was employed to correlate hot-natured TCMs with cardiovascular conditions and cold-natured TCMs with inflammatory diseases. Key compounds within cold-natured herbs were identified using LC-QTOF-MS/MS and analyzed through GNPS molecular networking. Target prediction was conducted using SwissTargetPrediction and ETCM, while inflammation-related targets were curated from OMIM, GeneCards, and DisGeNet. A PPI network was constructed in Cytoscape, and compound-disease overlaps were analyzed via GO and KEGG enrichment. Molecular docking and dynamics simulations were performed to confirm compound-target interactions.
Results: A total of 95 hot-natured herbs were found to contain 36 terpenoids associated with four major circulatory disorders. Additionally, 16 metabolites derived from Panax species exhibited potential anti-fatigue and cardiovascular benefits. Analysis of 79 heat-clearing herbs identified 50 flavonoid-O-glycosides with notable anti-inflammatory activity. Molecular profiling of 17 representative herbs revealed 418 distinct compounds, which were mapped to 1,380 compound-related and 895 disease-associated targets, yielding 255 overlapping targets. IL6 was identified as a central inflammatory node, with key enriched pathways including EGFR tyrosine kinase inhibitor resistance, PD-L1/PD-1 immune checkpoint regulation, and AGE-RAGE signaling. Molecular docking and dynamics simulations confirmed stable binding interactions, particularly involving IL6 residues PHE74, LEU178, and ARG179.
Conclusion: This study offers substantive evidence for the biochemical underpinnings of TCM’s cold-hot classification, revealing distinct molecular signatures aligned with their therapeutic roles. Hot-natured herbs were enriched in terpenoids associated with circulatory conditions, while cold-natured, heat-clearing herbs contained flavonoid-O-glycosides targeting inflammatory pathways, notably via IL6 modulation. The integration of metabolomics, molecular networking, and systems pharmacology provides a robust framework for elucidating TCM mechanisms, supporting its scientific validation and translational relevance in modern drug discovery.