LC-MS-Based Serum Pharmacochemistry Combined With Network Pharmacology and Pharmacodynamics to Evaluate the Role of Macromolecular Components in TCMs' Decoction: A Case Study on Qi-Huo-Yi-Fei Decoction for COPD Therapy.
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引用次数: 0
Abstract
Introduction: The role of macromolecular components in traditional Chinese medicines (TCMs) decoction remains poorly understood, primarily because of their structural complexity and limited systemic bioavailability. In the modernization of TCMs' decoctions, macromolecular components are often removed as "poor bioavailable impurities" by ethanol precipitation that might attenuate the efficacy thereof.
Purpose: A novel strategy integrating LC-MS-based serum pharmacochemistry, network pharmacology, and pharmacodynamics was developed to reveal the role of macromolecular components in TCMs' decoction, using Qi-Huo-Yi-Fei decoction (QH) treating chronic obstructive pulmonary disease (COPD) as a case study.
Materials and methods: QH was separated into macromolecular components (QH-M) and small molecular components (QH-S) by ethanol precipitation. The absorbed components of QH and QH-S in serum were qualitatively and semiquantitatively analyzed by UPLC-QTOF-MS/MS. The differences in targets and pathways of the absorbed components were predicted by network pharmacology analysis. The therapeutic effects on pulmonary function, histopathology, and inflammation of QH, QH-S, and QH-M were comparatively investigated on a COPD rat model.
Result: A total of 103 components were identified in QH and QH-S, whereas 86 and 72 were detectable in QH- or QH-S-treated serum, respectively. The highest levels of absorbed components appeared from 15 to 60 min for QH-S and at 15 min for QH. The concentrations of most absorbed components of QH were twofold higher than those of QH-S. Their protein-protein interaction (PPI), herb-component-target networks, and GO/KEGG enrichment pathways were quite different, mainly in inflammatory, immunity, and cell apoptosis processes. QH-M improved pulmonary function, histopathology, and inflammatory infiltration, mainly on FVC (p < 0.05), thickness/external diameter (p < 0.01), Wac/Pbm (p < 0.01), TNF-α (p < 0.01), and IL-17 (p < 0.05). Meanwhile, QH was more effective than QH-S, mainly on FEV0.3/FVC, MAN, GC/CC, TNF-α, and IL-17.
Conclusion: QH-M was not only effective independently on COPD but also showed integrative effects with the coexisting QH-S in improving their absorption, thus strengthening the component-target interactions, and consequently contributing to the COPD therapeutic effects of QH. Therefore, it was confirmed that QH-M was essential for QH's COPD therapy and should not be removed during the modern preparation development.
期刊介绍：
Phytochemical Analysis is devoted to the publication of original articles concerning the development, improvement, validation and/or extension of application of analytical methodology in the plant sciences. The spectrum of coverage is broad, encompassing methods and techniques relevant to the detection (including bio-screening), extraction, separation, purification, identification and quantification of compounds in plant biochemistry, plant cellular and molecular biology, plant biotechnology, the food sciences, agriculture and horticulture. The Journal publishes papers describing significant novelty in the analysis of whole plants (including algae), plant cells, tissues and organs, plant-derived extracts and plant products (including those which have been partially or completely refined for use in the food, agrochemical, pharmaceutical and related industries). All forms of physical, chemical, biochemical, spectroscopic, radiometric, electrometric, chromatographic, metabolomic and chemometric investigations of plant products (monomeric species as well as polymeric molecules such as nucleic acids, proteins, lipids and carbohydrates) are included within the remit of the Journal. Papers dealing with novel methods relating to areas such as data handling/ data mining in plant sciences will also be welcomed.
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