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| Study on the intervention mechanism against multidrug-resistant Pseudomonas aeruginosa by Fuzheng Touxie Jiedu Huayu Formula based on LC-MS/MS and target network |
| Hits 354 Download times 243 Received:May 20, 2023 |
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| DOI
10.11656/j.issn.1672-1519.2023.10.17 |
| Key Words
Fuzheng Touxie Jiedu Huayu Formula;Pseudomonas aeruginosa;multidrug-resistant;drug targets network;combination of drugs;antibacterial |
| Author Name | Affiliation | E-mail | | LIU Tong | Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
Beijing University of Chinese Medicine, Beijing 100029, China | | | LI Yan | Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China | 13011097949@126.com | | XU Hongri | Department of Emergency and Intensive Care Unit, the Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100029, China
Institute of Sepsis, Beijing University of Chinese Medicine, Beijing 100029, China | soohongil@sina.com | | LI Yali | Department of Emergency and Intensive Care Unit, the Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100029, China | | | HAO Dandan | Beijing University of Chinese Medicine, Beijing 100029, China | | | LIU Fengyi | Beijing University of Chinese Medicine, Beijing 100029, China | | | YANG Lijuan | Beijing University of Chinese Medicine, Beijing 100029, China | |
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| Abstract
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| [Objective] To investigate the pharmacodynamic material basis and direct/synergistic mechanism of Fuzheng Touxie Jiedu Huayu Formula in vitro intervention against multidrug-resistant Pseudomonas aeruginosa at the drug targets level. [Methods] The chemical components of Fuzheng Touxie Jiedu Huayu Formula were screened by LC-MS/MS and TCMSP database. The protein targets of the above components as well as imipenem，ceftazidime and ciprofloxacin acting on Pseudomonas aeruginosa were identified by Stitch database. Cytoscape 3.9.1 software was used to construct “herbal-chemical composition-target network” and “protein-protein interaction network”. Venn diagrams were used to screen the formula for co-acting targets with antibacterial drugs. GO functional enrichment analysis and KEGG pathway enrichment analysis of the targets were performed with the aid of the DAVID database. [Results] A total of 108 chemical components were identified by LC-MS/MS，155 chemical components were screened from the TCMSP database，and 162 chemical components were obtained after de-duplication，of which 42 chemical components were able to act directly on 240 target proteins of Pseudomonas aeruginosa. 17 core components were screened by network pharmacology，mainly flavonoids，sterols，and terpenoids，among which β-sitosterol，quercetin，and luteolin have higher degree. This formula has 3/3/17 common targets with imipenem，ceftazidime，and ciprofloxacin，and 2 common targets for the 4 drugs. The common targets of actions are mainly in the pathways of bacterial energy and biochemical metabolism，DNA and genetic material replication，protein function，and surface polysaccharide formation. GO and KEGG enrichment analyses suggested that this formula is mainly related to the regulation of bacterial energy and biochemical metabolism，the regulation of DNA/protein homeostasis，the influence on the bacterial cytoplasmic membrane，and the intervention in the synthesis of surface polysaccharides and biofilms，which play a protective role for bacteria. [Conclusion] Fuzheng Touxie Jiedu Huayu Formula has multi-component，multi-target，and multi-channel interventions with Pseudomonas aeruginosa，and the main intervening chemical components are mainly flavonoids，sterols，and terpenoids. The mechanism of direct/synergistic antibacterial drug interventions on Pseudomonas aeruginosa is related to the influence of bacterial genetics，metabolism，biofilm formation，etc. This study provided some ideas and references for the development of antibacterial drugs from natural drugs at the drug targets level. |
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